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Yale Scientific Magazine











The Milky Way Galaxy has long been

studied as a model for other galaxies

in the universe. However, Yale professor

Marla Geha is part of a collaboration

exploring just how different the

Milky Way might actually be




Researchers at Yale University have

developed a new way to study

proteins, which led to discovering

the function of BRCA1 breast cancer

genes and its interaction with other

genes in the role of tumor expression



Yale scientists found two potential

enymes to target via cell therapy to

tret the common variety of Parkinson’s

disease with Gaucher disease.

These two enzymes regulate the pathology

of the specific lipids that accumulate

due to Gaucher disease



New disovery in skull and brain development

in skull and brain development

has implications for greater

understanding of evoloution of reptiles

and birds



The communiction between nervous,

immune and metabloic systems

changes as people age. A team led

by Christina Carmell and Vishwa Deep

Dixit of the Yale School of Medicine

disovered a subset of microphages

that could open the door to new strategies

to keep people healthier longer

More articles available online at www.yalescientific.org

December 2017

Yale Scientific Magazine


q a



Even isolated islands such as the

Galápagos are affected by anthropogenic

environmental change. Unfortunately,

one affected group is the Galápagos giant

tortoises, whose populations have decreased

by ninety percent in the past three

centuries, in large part due to hunting in

recent years. The C. elephantopus species

from Floreana Island is considered

extinct, and the C. abingdoni from Pinta

Island recently joined its ranks in 2012,

when the last individual, named Lonesome

George, died. However, a November

2015 international expedition to the

remote Galápagos Islands provides hope

that these extinct tortoises can be revived.

Researchers from Yale went on an expedition

to Isabela Island to locate descendants

of the original Floreana and

Pinta tortoises. These tortoises were likely

thrown off ships by mariners onto

Can we bring back extinct Galapagos turtles?


►Lonesome George was the last Pinta Island

tortoise. His death in 2012 marked the extinction of

another species of the Galápagos giant tortoise.

non-native habitats where, over generations,

they mixed with the native species

to create genetic archives of the now-extinct

species. After analyzing the DNA of

150 tortoises, researchers identified 65

with strong ancestral connections to the

Floreana tortoise, 23 of which now reside

in a captive breeding center.

The Floreana tortoise breeding program

is expected to generate thousands

of offspring for the Floreana Island. For

the first time in 150 years, these mega-herbivores

can be returned to their

native land, returning balance to the ecosystem.

“It is a really exciting prospect to

restore a species that we once thought

was extinct,” said Dr. Joshua Miller, a

member of the 2015 expedition and a

current postdoctoral researcher at the

Yale Department of Ecology and Evolutionary



There are many forms of alternative

energy, ranging from solar to

wind. A problem with these forms of

energy, however, is that their availability

is inconsistent, so they must

often be stored for future use. But

what if there were an alternative energy

resource that is available consistently,

all day, every day? Scientists at

Columbia think that the evaporation

of water from lakes might just be that

energy resource.

The scientists at Columbia used B.

subtilis, a common soil bacterium,

to harness the energy released from

evaporating water. B. subtilis forms

spores—a hardy, dormant form of

the bacterium—that expand and

contract in response to relative humidity

in the environment. The researchers

plated these spores onto

small films that could contract with

them. By altering humidity levels in

Can evaporation drive energy production?


►Researchers at Columbia have high hopes for

bacterial colonies that can produce mechanical

energy in response to evaporated water.

the environment, they were able to

induce expansion and contraction

in the spores and thus in the films.

As the films expanded and contracted,

similarly to human muscle,

the motion could be converted into

an energy strong enough to turn on

a small LED light bulb or to power

a small car.

While this technology is incredibly

promising, it’s still a long way

off from serving the public. Details

ranging from how to implement

large scale construction of these

devices to how to circumvent the

legal issues surrounding water access

rights prevent this invention

from becoming a part of your local

community lake tomorrow. However,

this technology poses a lucrative

alternative to fossil fuels, and

maybe even to other forms of environmentally

friendly energy.



We are natural storytellers, and science is one of the best stories to tell.

After all, science is full of noble quests to discover the secrets of our natural world. The

characters of science are fascinating: some quirky, most kind, all with a burning passion for

their labor of love. And the stakes of science can be high, ranging from the privacy of our

digital lives to cures for rare and debilitating diseases.

In every issue, we seek to uncover the most fascinating breakthroughs in science. From

seeing how lizard skulls evolved into bird skulls (p. 20) to understanding Parkinson’s disease

by studying a much rarer cousin of the disease (p. 18), the journey of science ranges over a

very wide span of topics. Our cover article this issue describes the galaxy that we live in, and

why researchers believe that it is rather unique compared to other galaxies (p. 12). We also

pursue the deadly killer of breast cancer and seek to understand how one gene, BRCA1, is

able to cause so much damage (p. 15). And we even fight death itself, learning how our bodies

break down with age to find ways to keep the old healthy (p. 22).

While the results of science can make our lives more fulfilling, the journey to reach there

can be equally exciting. The methods of modern scientific exploration - using lasers to probe

neurons (p. 26), creating breathalyzers to monitor exercise (p. 35), or programming bacteria

to grow proteins (p. 32) - challenges our imagination. The diligent scientists who work at

these goals are just as amazing, from undergraduate who work on cell structures (p. 36) to

doctors who fight disease and discrimination (p. 37). Every advancement in science is made

by groups of researchers struggling to solve mysteries of our world. Their tales inspire us to

do the impossible and persevere in the face of challenges.

And science is always relevant. New innovations create safer ways to replace dangerous oil

pipes (p. 7) and create better vaccines to fight off the flu (p. 9). And beyond the endless new

biomedical and engineering technologies, other discoveries - on the origin of diseases (p. 11)

or the rescue of monkeys (p. 6) - define our human spirit.

We write because the story of science fascinates us. New discoveries challenge past paradigms

and propose new world-views, as scientists aim to discover more fundamental truths

in our study of the universe. These stories have impact far greater than merely other scientists,

influencing the fundamental beliefs of humanity.

As this year draws to a close, we thank you for being with us as we have explored these stories

together. Our staff and masthead have tirelessly worked to write, produce, edit, design,

and publish this magazine, and we could not have told these stories without a willing listener.

We are excited for the many more science stories to be told in 2018, and to continue being

part of this fantastic community of scholars and friends.


Chunyang Ding


Since this is my final cover as Arts Editor, I

just want to thank everyone who ever picked

up a copy of the YSM in the last 12 months

for giving me a chance. Just kidding, it’s really

thanks to the incredible production and writing/editing

team that this magazine is what it

is today — so thank you all for giving me the

chance to draw galaxies, DNA, mushrooms

and more. I’ve grown as an artist and as a fan

of this magazine with each issue, and I hope

that this final cover design — a fanciful depiction

of a prism of light through our very

own Milky Way — articulates that feeling.


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in brief

Cayo Santiago: No Monkeying Around

By Sarim Abbas


►The monkeys of Cayo Santiago

comprise some of the best-studied

primates on the planet.

Off the coast of Puerto Rico lies Cayo Santiago,

a 38-acre island home to one of the oldest

primate field sites in the world. But in the

aftermath of Hurricane Maria, the well-being

of its locals and monkey population is at risk.

Scientists have studied Cayo Santiago’s

monkeys for decades, looking at group dynamics,

development and genetics. “It’s one

of the only sites in the world with such a

large population of habituated monkeys,”

said Laurie Santos, a psychology professor

at Yale University who studies animal cognition.

“It’s really the one site where I can

do my cognitive studies of primates on that

large a sample.”

The island is a mere 38 acres, and the monkey

residents can roam freely on the island

without fear from predators. Scientists from

at least nine universities work on the island,

including faculty from Yale Universiy and

the University of Puerto Rico.

But on September 20th, the island’s monkey

population and locals were in the direct

path of Hurricane Maria, a hurricane that

ravaged much of the Caribbean. Now, researchers

and affiliates are rushing to ship

food, clothes and other supplies to help aid


Though all monkey groups on the island

have been accounted for, the devastation

to infrastructure, vegetation and fresh-water

sources will no doubt impede their livelihood.

And for many locals—most of them

in the researchers’ employ—the situation is

even more dire. “Some of our long-term staff

and their families have lost everything they

own,” Santos said, “and everyone in the town

has not had power, phone service, or water

for an entire month.”

Despite lackluster official support, researchers

hope their shipment of supplies

will help alleviate the hardship. But until the

locals get back on their feet, all operations on

the island remain on hold.

Hot and Cold: Temperature and Virus Transmission

By Daniel Fridman


►Aedes aegypti mosquitos spread

many diseases, including DENV-2,

chikungunya, Zika, and yellow fever


In recent years, news has covered the

emergence and spread of mosquito-transmitted

viruses including Zika, chikungunya, and

dengue. Scientists and public health officials

work to understand, predict, and ultimately

prevent outbreaks. A new Yale study, conducted

as a collaboration between the labs of Paul

Turner and Jeffrey Powell in the department of

Ecology and Evolutionary Biology, investigated

the effect of temperature and mosquito genotype

on the infection rates of Aedes aegypti mosquitos

by a type of dengue virus (DENV-2).

Knowing that temperature affects mosquito

susceptibility to infection, the researchers sought

to determine how various mosquito and viral

genotypes affect infection rates at different

temperatures. The researchers studied two

populations of the A. aegypti mosquito from two

locations in Vietnam—Hanoi and Ho Chi Minh

City, with average temperatures of 23°C and

28°C respectively—and infected them with two

isolates of DENV-2 originating from the same


“There is a lot of variation in temperature

in these regions,” said Andrea Gloria-Soria, a

member of Turner’s lab and first author of the

study. “We hypothesized that mosquitos adapt

to the temperature where they live, affecting

virus transmission.” After a 10-day incubation

at temperatures of 25°C, 27°C, or 32°C, the

researchers quantified the number of mosquitos

infected with dengue virus. Their findings showed

that different mosquito populations respond

differently to temperature, with mosquitos from

warmer climates being more susceptible to

DENV-2 infection at colder temperatures.

Local temperatures may influence the risk of

dengue virus outbreaks, and introduction of

mosquitos adapted to warmer climates to cooler

geographic areas may increase infection rates.

“Many people in cooler regions don’t think about

mosquito viruses as a problem, but if mosquitos

are introduced at the right moment, they can

survive and transmit the virus, presenting a

greater risk for outbreaks,” said Gloria-Soria.

6 Yale Scientific Magazine April 2017 www.yalescientific.org

in brief


Solarizing Through Social Networks

By Ashwin Chetty

If your friend installed solar panels, you

most likely would too. Recently, researchers

investigated community campaigns in

Connecticut that took advantage of these

effects, in a study led by Duke professor

Bryan Bollinger and Yale professor Kenneth

Gillingham. They found that increased

visibility of solar panels in neighborhoods,

word-of-mouth campaigns, and town events

can make solar installation “contagious.”

The Solar Energy Evolution and Diffusion

Studies 1 (SEEDS 1) project focused on

analyzing Solarize campaigns, which aim

to increase solar adoption. Specifically, the

researchers studied Solarize campaigns in

Connecticut that used two main strategies:

grassroots marketing and group pricing, a

pricing scheme that reduces cost of solar

installation as more people install solar

panels. Gillingham and Bollinger found that

group pricing did not lead to increased solar

installation. However, 20-week campaigns

were more effective than 10-week campaigns

by allowing for more word-of-mouth.

Gillingham and Bollinger are now working

on a SEEDS 2 project, asking another research

question: “How can these campaigns reach

low and moderate-income households?” Their

hypothesis is that changing the messaging of

the campaign to focus on either the community

aspect or the financial attractiveness of solar

installation will increase solar adoption in

these households. In South Carolina, they

are investigating whether access to shared

solar—owning a share of a solar farm instead

of installing panels on a rooftop—increases

solar adoptions by low and moderate-income


“In the past, people have just run the

campaigns, and we were the first ever to test

how to run the campaigns,” Gillingham said.

Even though the research is still ongoing, solar

advocates can immediately apply these findings

in solar adoption campaigns around the country.


►Gillingham and Bollinger found

that increasing solar planet visiblity

through local outreach efforts can

increase solar installation.

Yale Startup Hopes to Deploy Pipe-Inspecting Robots

By Linh He

Big changes are on the way in the petroleum

industry. Soon, a new player will help detect

pipeline corrosion: robots. Dianna Liu, a

former Exxon-Mobil worker and now Yale

School of Management student, founded the

company ARIX with recent Yale graduates

Petter Wehlin ’17 and Bryan Duerfeldt ’17 to

explore how robotics and predictive analytics

technology could be tapped for the oil


“Like any large company that deals with

operations…[the petroleum industry] is very

dangerous, and they prioritize safety,” Liu said.

However, limited technology exists to ensure

the safety of workers searching for corrosion

in the pipelines that carry petroleum. Liu, who

previously interned in a biomedical company,

was inspired by how technology has improved

the quality of medicine, and wanted to apply

technology to the petroleum industry as well.

Her idea was a promising solution that

holds potential in tackling a $5.4 billion

dollar corrosion issue within the U.S. oil and

gas industry. ARIX’s robots could prevent

human workers from undergoing dangerous

processes to inspect pipe corrosion in

petroleum plants. Rather than having human

workers hang by ropes and walk on unstable

scaffolding to inspect pipes, ARIX proposes

using robots that could travel on the outside

of the pipes while inspecting specific points

along the pipeline. Furthermore, ARIX’s robot

inspection technology can quickly provide

more comprehensive data than people could.

ARIX has received much attention since its

founding. The prototype technology received

the $25,000 Miller Prize from the Tsai Center

for Innovative Thinking at Yale, and has

gained recognition from companies and

investors. While still in its early developing

stages, ARIX has already caught the interest

of the petroleum industry. For now, ARIX

will continue focusing on fine-tuning

the technology, and in the long run, will

potentially look to apply the technology to

other industries beyond gas and oil.


►Dianna Liu (center), Petter Wehlin

(right), and Bryan Duerfeldt (left) are the

three co-founders of ARIX.


April 2017

Yale Scientific Magazine





Fighting fungi by capturing sugars


For many Yale students, the word “fungus” might call to

mind the dining hall’s hybrid mushroom and beef burgers.

But fungus also has another unsavory meaning—fungal infections

are a major public health concern and can be deadly,

particularly to patients with weak immune systems such as

those with organ transplants, HIV, or cancer.

Fungal infections are responsible for roughly half of

AIDS-related deaths globally Candidemia, a fungal infection

common in organ transplant patients, has a 30-40% mortality

rate. While antifungal treatments exist, they can have side

effects, similar to how chemotherapy can damage a cancer

patient’s body while destroying cancer cells. Furthermore,

fungi are capable of developing resistance to conventional


Dr. Egor Chirkin and Dr. Viswanathan Muthusamy, researchers

in the Spiegel lab of the Yale Chemistry department,

collaborated with Merck to generate a novel antifungal

compound that would minimize such side effects and prevent

the development of resistance. Their recent paper describes

how Chirkin and Muthusamy designed and tested a

compound that can activate the body’s own immune system,

destroying fungal cells without harming the patient’s own


“What the field is moving toward is clean killing of pathogenic

cells without a lot of side effects,” said Muthusamy, who

headed the biology aspect of the study. “What better to do it

with than your own immune cells, which are meant to fight

these diseases?”

The scientists were able to harness the power of the immune

system by creating a small molecule with two different

ends, so that one end of the molecule binds to the fungus,

and the other to antibodies already present in human blood.

“On one side, we need something which can always interact

with antibodies, the antibody-recruiting terminus.

On the other side, we need something which can interact

with the pathological cells, some specific target which is expressed

only on the fungal cell wall,” said Chirkin, who used

his chemistry background to design and synthesize potential


The researchers began by creating modified versions of a

molecule called calcofluor, which selectively binds to chitin,

a sugar found in fungal cell walls but not human cells. Because

there was not a good test to measure the efficacy of

the molecules Chirkin created, Muthusamy devised a novel

test. The common human pathogen C. albicans was treated

with different antibody-recruiting molecules targeting fungi

(ARM-Fs). When the ARM-F was able to recruit antibodies

to the fungal cell, the complex could be recognized and

“eaten up” by human immune cells. Looking for fluorescently

labeled fungal cells, the scientists were able to quantify how

efficiently the fungal cells were eaten up by the immune cells.

“It is very unique in biology to target fungal cells using

immune effectors; it is not usual in the literature, so we had

to develop our own assays to test the efficacy of these compounds,”

said Muthusamy. This new methodology can be

used by scientists in the future to continue study in the field.

In addition to avoiding side effects, an advantage to the

ARM-F approach is that fungi are unlikely to develop drug

resistance. Unlike common antibiotics, which quickly become

obsolete, an ARM-F drug could likely be used without

drug resistant strains developing. Chitin, the target molecule

on fungal cell walls, is a sugar polymer. While proteins evolve

quickly to evade our immune defense system due to errors

in DNA replication, sugars are not coded for by DNA and

therefore do not possess the same ability to quickly mutate.

“Chitin is a key element of the fungal cell wall, and it is

a polysaccharide. This is a chemical substance, so the fungus

really cannot change it. The fungus can make less of

it, but that also would reduce its chance of survival,” said


Moreover, small molecules tend to be more stable than

other drug compounds and can be ingested, unlike biological

molecules. This means that a drug from an ARM-F could

likely be taken orally as a pill—much easier than an injection

or other delivery method.

While this study holds promise, the molecule must undergo

further testing before it can be used on patients. So far, the

ARM-F has only been tested in cells. The molecule must next

undergo rigorous testing in mouse models before entering

clinical trials. If all goes well, many patients stand to benefit

from this work.

►Candida albicans is a common fungal pathogen.


8 Yale Scientific Magazine December 2017 www.yalescientific.org




A new direction in bioinformatics



►A nurse prepares a flu shot, inserting the vaccine into a

needle syringe.

Each year, 132 million Americans flock to doctors’ offices,

pharmacies, and clinics for flu shots. With the onset

of “flu season” each year, 41% of the population opts to

get vaccinated. Currently, flu shots are the most effective

way to protect against infection. Despite this, they are only

about 60% effective in adults over the age of 65.

Why does the flu vaccine work for some, and not for others?

The answer, according to a recent study, may lie in our

genes. Dr. Albert Shaw led scientists at Yale University and

four other research centers to find that certain genes correlate

to stronger immune responses. This discovery paves

the road for further genetic research and provides insight

into the future of vaccination.

“We set out to study why people respond differently to

the vaccines. We used the flu vaccine because it is very

commonly used throughout the country and you can collect

a large number of patients,” said Ruth Montgomery,

co-author of the study and associate professor at the Yale

School of Medicine. As Montgomery implied, an important

aspect of the study is its size. The genetic data used

came from four independent institutions. In total, over 500

individuals participated in the study. The data spans five

years of flu vaccination seasons. In combination, these factors

make the conclusions of the study more reliable.

“A big part of our study was comparing responses to vaccination

with younger and older people. In general, older

people have a much less efficient and successful response

to vaccination,” Montgomery said. The ages of the participants

fell into two groups: either under 35 or above 60

years old. Interestingly, the results for the study differed

between the two age groups. The cluster of genes, or “signature,”

that correlated to a stronger immune response in

younger people did not help the older group. Similarly, the

beneficial signatures for the older group did not prove significant

to the younger group. “The older people who respond

use different genes and cellular pathways than the

younger people who respond,” said Montgomery. This

means that our immune responses to vaccination change

with age—a potential subject for further investigation.

The researchers identified the genes that influenced immune

response by examining the younger people that did

not respond well to vaccination. Nine individual genes and

three sets of co-expressed genes were found to impact response

to the flu vaccine. “The beauty of this study was

combining those young non-responders across a number

of different universities and research programs and using

computational tools to try to understand what might

lead to a poor vaccine response in a young healthy donor,”

Montgomery said.

Montgomery cites much of the study’s success to our increased

ability to use computational processes to analyze

biological data. Researchers gathered 47,000 RNA transcripts,

which are a form of genetic information in our

cells, from each patient. With over 500 participants in the

study, this amounts to more than 23 million transcripts in

total. Without the aid of computer algorithms, this massive

amount of data would be impossible to process. With

the bioinformatics analysis led by Dr. Steven Kleinstein,

researchers were able to synthesize the data and make significant


The results of this study point to possible innovations in

vaccination. With the knowledge that older people process

vaccines differently from younger people, scientists

may develop different methods to boost the effectiveness

of vaccines for older people. “It is possible for some sort of

therapeutic approach to boost those immune responses—

or perhaps with a better understanding of the pathways, we

can modify what goes into the vaccination for older people,”

Montgomery said.

Since the study only examined the flu vaccine, scientists

are not yet sure if these genes help in immune responses

to other vaccines. “It’s not always clear whether the results

from this study will apply to responses to other vaccines,

so that would require more study to understand,” she said.

All in all, the work of these collaborators provides exciting

insight into the genetics behind immune response and

opens new doors for future research on vaccines.


December 2017

Yale Scientific Magazine



applied physics


Acoustics may contribute to the next computing revolution



►The current state of building a quantum computer. Quantum

computers must be kept in extremely cold environments to

prevent heat from being absorbed by the system, which disrupts

quantum states.

Potentially the most powerful computing tool ever created,

quantum computing technology is likely to continue

to advance in the coming decades. What makes quantum

technology special is its computational power, allowing it

to have a wide range of applications. Among these are the

abilities to break RSA encryptions, which are used by many

governments to encode information on a classical computer,

and to analyze vast amounts of data very quickly.

However, building a quantum computer is difficult because

it poses the challenge of finding a system efficient for

both quantum information processing and effective control

of quantum states. Recently, a collaborative effort by

the Schoelkopf Lab and Rakich Lab at the Yale Quantum

Institute has shown promise in using sound waves to store

quantum information. Their method would increase efficiency

and reduce production costs, which could cause major

advances in the field of quantum computing.

For the last eighty years, the world has relied on classical

computers, which operate using values of zero and one to

store information and solve problems that cannot be worked

out by hand. Classical computers use two-state physical systems,

like transducers or magnets, to define the complete

physical state of a system, and then apply algorithms to manipulate

those states to solve different problems.

Quantum computing breaks from the realm of classical

computing by utilizing the fundamentals of quantum mechanics

to encode information. For a quantum particle with

two possible states, a particle is said to be in a superposition

of both states, meaning the particle can be in both at

the same time. Upon measurement, the particle randomly

chooses one of these states.

These particles are called qubits, or quantum bits, and are

quantum representations of a physical system. Just like a

classical bit, a qubit is a piece of information that can be

used in computation. However, instead of dealing with certainty,

quantum physics deals with probabilities, and thus

the state of the qubit is a probabilistic representation of the

two possible states it could occupy. Using these odd probabilities,

quantum computers can solve complex problems,

including breaking computer encryptions to access secret

data. The possibilities are endless.

Some of the most difficult challenges with quantum computing

are maintaining a particular quantum state and finding

a physical system that can be used to store quantum information.

This is because quantum states are very fragile

and are susceptible to change by any interaction with the

environment around them.

In September 2017, the Schoelkopf Lab and Rakich Lab

at the Yale Quantum Institute announced their success using

a simple-to-produce and very robust device that uses

sound waves to store quantum information. The apparatus

uses a piezoelectric transducer to couple the qubits to

sound waves. The qubit system shows a dramatic increase

in coherence time from previously demonstrated experiments,

giving scientists more control and predictive power

over the qubit.

Furthermore, the apparatus used to couple the qubits to

sound waves requires relatively simple fabrication methods.

“I think that our work demonstrates that it’s possible

to couple superconducting quantum circuits and mechanical

resonators in a simple and high-performance way,” said

Yiwen Chu, lead author of the recent breakthrough and

a post-doctoral researcher in the Schoelkopf Lab. “This

makes them accessible and robust enough to be used in

more complex quantum devices in the future.”

This finding comes at an important and exciting time

in the development of quantum mechanical applications.

“Quantum computing is one of the main examples of how

we can harness quantum mechanics to do something useful,”

said Chu. “Much like other applications of physics,

quantum mechanics is also undergoing that exciting transition

from us being able to understand the physics to being

able to build something useful.”

As quantum systems become more complex and demonstrate

more precise control of qubits, the ultimate goal of

building a quantum computer able to solve even more complex

problems than currently possible will become a reality.

Contributions like this will prove to be the key to their progression

into a more mature and feasible application, making

the once most difficult problems seem trivial.


Yale Scientific Magazine December 2017 www.yalescientific.org

evolutionary biology



Human activity likely affects the spread of Lyme disease



►Black-legged deer tick on a blade of grass. Ticks are the

main vectors of Lyme disease

Local Connecticut lore names Plum Island, the home of a high

security government laboratory, as the source of Lyme disease.

The controversial theory claims that infected ticks were accidentally

released from the facility in the early 1970s. The truth, however,

may be more compelling. Recent research, led by Katherine

Walter of the Yale Department of Epidemiology and Microbial

Diseases, suggests that the pathogen has existed for around 60,000

years. Furthermore, it may be human impact, not scientific meddling,

that has caused the sudden surge in sickness.

Strange things appeared to be afoot in Lyme, Connecticut

during the summer of 1976. The town had experienced

a record number of juvenile arthritis cases that year, which

puzzled many physicians and researchers. To make matters

worse, complaints of severe joint pain, headaches, and fever

were spreading like wildfire. What had begun as an isolated

incident swiftly transitioned into a widespread phenomenon,

affecting adults at the same rate it has children.

The mysterious symptoms were later all classified under one

ailment: Lyme disease. Named for the town first believed to be

its epicenter, Lyme is now reported to be the most common vector-born

disease in the United States. According to the Center

for Disease Control and Prevention, there were over 28,000 confirmed

cases in 2015 alone. To examine the spread of Lyme however,

one must first examine its vector, the blacklegged tick.

When one thinks of ticks, the connotation tends to be quite

negative. These small parasites are the often invisible threat

associated with outdoor activity in the late summer and fall.

Their resemblance to spiders, with which they share the same

subclass, is equally unnerving. What makes the blacklegged

tick potentially dangerous however, is the pathogen it carries.

First clinically described in 1982, Borrelia burgdorferi is one

of the few bacteria that seems to directly interact with the cell

tissues it infects, rather than producing a microbial toxin. It

also has an extremely low rate of replication, which allows it

to remain undetected in a host for some time. This creates

difficulties in prescribing treatment, as many patients are unaware

of the infection until it becomes chronic.

Although researchers now have an understanding of the

effects of a B. burgdorferi infection, little is known about

its evolutionary origins. Additionally, it is still unclear why

the United States has seen such a rapid increase of Lyme in

the past 30 years. Walter and her team at Yale have attempted

to expand the current understanding the bacterium.

Walter became interested in the pathogen’s history while a

graduate student in the Yale Department of Epidemiology

and Microbial Diseases. “Looking at molecular evolution

is like looking at records,” Walter said. “Often, the records

for infectious diseases are incomplete.” Her research team

attempted to explain the sudden surge of illness by examining

the genome of B. burgdorferi, using data compiled from

nearly thirty years of fieldwork.

The results of the research proved to be astonishing. They

suggested that B. burgdorferi has been present in the northeastern

United States for around 60,000 years. This differs

from the original theories, which tend to focus on evolutionary

change or pathogen introduction as the cause of its emergence.

Furthermore, the findings point to human activity as

the leading factor in Lyme’s dispersal.

To put this into perspective, imagine the northeast 60,000

years ago. It did not contain the vast expanse of cities and roadways

characteristic of today. The landscape was likely composed

of forests and thick underbrush, making it an oasis for

ticks. Urban development and industrialization have greatly

infringed upon the habitat of the animal hosts, and therefore,

of the tick. In addition, climate change has contributed to consistently

warmer seasons, which in turn have afforded ticks a

longer lifespan. Ironically, while global warming may prove

detrimental to humans, it will promote the survival of parasites.

Increased vigor, as well as sustained migration, will continue

to broaden the scope of Lyme disease in the near future.

There is, however, a glimmer of hope. A research team

from the Cary Institute of Ecosystems found that ticks

seem to dislike dry weather. Nymphs, the intermediate

stage in a tick’s lifespan, experience more difficulty securing

hosts in arid conditions.

If the United States continues to see a decrease in annual

precipitation, it may also see a decline in the prevalence of

Lyme disease. For now, scientists like Walter and her team will

continue to track and study the disease, helping us better understand

our relationship with the environment around us.


December 2017

Yale Scientific Magazine


astronomy FOCUS

Imagine sitting at a movie theater watching the latest blockbuster movie about space. Because

of its vast size, a galaxy pulls in smaller and slower-moving galaxies, trapping them in its orbit.

Eventually this larger galaxy begins stripping away bits of mass from the smaller galaxies and,

eventually, its own stars. You find yourself sitting at the edge of your seat, awaiting what happens.

As exciting as this phenomenon seems, it’s not science fiction, but reality. What’s more, it’s

not just any galaxy—it’s our very own Milky Way.

Galaxies are born in dark matter, a mysterious

substance that comprises about

90% of our universe. The Milky Way is a

central galaxy, meaning it has smaller galaxies,

called satellites, caught in its gravitational

pull. Our galaxy has long been

studied to increase our understanding of

the universe. Specifically, researchers have

based their predictions about dark matter

and the formation of galaxies based

on their observations of the Milky Way’s

satellite population. However, researchers

have discovered that the Milky Way

might be an outlier. Marla Geha, professor

of astronomy at Yale University, is a

leader in this area of research—no other

research group has tried to do a project

as ambitious as hers, requiring extensive

time and resources. By studying 8 galaxies

similar to the Milky Way, Geha’s team

have provided researchers with incredible

new insight—the Milky Way Galaxy may

be more unique than we think.

A taste of the Milky Way galaxy

It is believed that galaxies form in the

center of dark matter structures. Galaxies

emit light from their stars—the more stars,

the brighter the galaxy. Within the Milky

Way, two satellite galaxies, called the Small

and Large Magellanic Clouds, are currently

forming stars from gas. All other satellites

have been stripped of their gas as the Milky

Way eats away at the materials composing

the satellites, a process that occurs when

smaller galaxies orbit the Milky Way.

Researchers have heavily based their predictions

about how galaxies form based off

their research on the Milky Way’s satellite

galaxies. However, Marla Geha, along with

Risa Wechsler, professor at Stanford University,

are interested in how the Milky Way

compares to other galaxies in our universe.

“We have a default assumption that whatever

is in our neighborhood is what we see

everywhere but maybe this isn’t the case,”

Weschler said. The behavior we see in our

own galaxy may not be typical of many other

galaxies in the universe.

The beginning of a SAGA


►The Magellanic Clouds are the only two

star-forming dwarf galaxies found orbiting.

Geha and Weschler, along with their research

team, were interested in exploring

other satellite galaxies beyond the Milky

Way. To investigate these other galaxies,

they started the “Satellites Around Galactic

Analogs” (SAGA) Survey. The purpose

of this survey is to investigate 100 galaxies

similar to the Milky Way galaxy and to

compare their satellite galaxies. Successfully

doing so has implications on how researchers

view galaxies. For example, satellite galaxies

are of interest because it may provide

clues about dark matter and its interaction

with galaxies. When satellite galaxies become

caught in the gravitational pull of

larger galaxies, it is likely dark matter is at

play, though it remains unknown how the

satellite becomes embedded in what is essentially

a halo of dark matter. Moreover,

the behavior of these satellites, such as their

ability to form stars, provides clues about

the relationship between dark matter and

satellites, and why some satellites have lost

the ability to actively form new stars.

To begin their research on both analog

galaxies and their satellites, the team used

already established catalogs to select galaxies

similar to the Milky Way. The researchers

based their criteria on how similar these galaxies

were in luminosity as well as whether

they had a similar large-scale environment.

Galaxies that passed these criteria were added

to the SAGA Survey for further analysis

of their satellite galaxies. Of all the galaxies

►The bright spots in the image are stars in

the Small Magellanic Cloud.

in the catalog, the team has so far added 79

galaxies to the SAGA and have fully investigated

satellites on eight of these analogs. The

next step is examining these galaxies more

closely and searching for embedded satellites

caught in the gravitational pull of these

galaxies which may provide clues of similarities

shared with the Milky Way.

A (red) shift in perspective


Researchers detect satellite galaxies

through their brightness, an indicator of

the number of stars within it. Images of

galaxies are readily available in published

research catalogs. The research team used a

method called photometry, a procedure to

detect light intensity from these galaxy images.

However, photometry poses a problem—there

is no way to tell whether this

galaxy is circling another galaxy. “It’s like

holding a series of galaxy images up of and

trying to decide which is a satellite—you

just can’t know,” Geha said. If researchers

could find a way to measure the distances

between these galaxies, they may be able to

uncover the behavior of these galaxies.

One method the research team used in

uncovering this data was to analyze the

spectra of the galaxies. By scattering the

light emitted by the galaxy, they were able

to observe the characteristic wavelengths of

the light energy emitted. Similar to scattering

white light with a prism to release its

rainbow colors, Geha and the team took

images of galaxies and separated the light


December 2017

Yale Scientific Magazine




into many different wavelengths, or colors.

Objects moving away from the Milky Way

emit less intense light and subsequently undergo

a shift in wavelength toward the red

end of the color spectra where wavelengths

are longer. Therefore, a galaxy with a larger

redshift is moving further away. By gathering

this information, the researchers were better

able to understand the position of potential

satellite galaxies, filling in the missing gap in

knowledge about whether these galaxies are

indeed satellites of a central galaxy.

However, using this process to obtain redshifts

comes with its own set of difficulties.

For example, spectroscopy is expensive and

time consuming. In addition, the slower

that a galaxy moves, the fainter and harder

it becomes to detect the redshifts. Though

the research team was able to target over

17,000 redshifts, the spectra obtained may

be not only from galaxies themselves, but

also from stars and other objects. Therefore,

they needed to further filter out the

redshifts corresponding to galaxies from

those caused by other natural phenomena.

To create a more efficient system for detecting

redshifts of galaxies, the researchers

observed the relative wavelengths of satellite

galaxies and their redshift range. They

found a range in which the redshifts were

similar among satellites, indicating that

redshifts in this range were the most likely

to correspond to satellite galaxies. By going

back over their collected sample of redshifts

and selecting redshifts that fell within

the “satellite galaxy” range, they were able

to leave out redshift data from unwanted

sources. Using this refined redshift information,

researchers were able to locate 25

satellites from analog galaxies, providing

us a new perspective on the nature of many

potential satellite galaxies in the universe.

The SAGA continues


►The Milky Way Galaxy has long been studied,

and houses numerous satellite galaxies.

While the study has surprised the research

team, there still remains much to

uncover, and they are just getting started.

The team is leading in this field—there

is no other research team doing such an

ambitious project. Once the SAGA is completed,

scientists will better understand

the Milky Way from a cosmological standpoint

and how it compares to other analogs.

“We’re really proud of the progress

we made and we are well underway in answering

the question of how atypical our

galaxy may be,” Geha said.

With a goal of analyzing 100 analog


►Using optical telescopes, more than

10,000 distant galaxies can be seen.

galaxies similar to the Milky Way, the researchers

are already analyzing the data

of other analogs for their satellites. With

more efficient methods for detecting redshifts,

the team can more effectively locate

even the faintest satellites. While Geha is

not certain what the rest of their data will

indicate once they finish analyzing all satellite

galaxies, she believes it might take as

few as two to four years to finish the survey

and make more conclusions. “Once

the SAGA Survey is complete, I think

we will really understand our galaxy in a

much broader context,” Geha said. Until

then, the SAGA continues in uncovering

the mystery of our galaxy.



The Milky Way Galaxy—an outlier?

The process of obtaining redshift information

to determine satellite galaxies is

a slow process, but it comes with a great

payoff. The team’s analyses of these satellite

galaxies have revealed an interesting finding:

the analog galaxies contain mostly star

forming satellite galaxies. Unlike the Milky

Way, the results from the 8 analog galaxies

indicated 26 of the 27 satellite galaxies are

actively forming stars. “If more information

supports this finding, we need to start

reevaluating how we view our own satellite

galaxies in the Milky Way,” Wechsler said.

JESSICA TRINH is a sophomore Neuroscience major in Branford College.

She is the Vice President of Synapse and is excited to teach middle schoolers

about STEM. She also teaches health education in New Haven middle schools,

nutrition counseling at HAVEN Free Clinic, and is currently leading a research

project on nutrition.


Wechsler for their time and enthusiasm for sharing their research.


Geha, M., Wechsler, R.H., Mao, Y.Y., et al. 2017. “The SAGA Survey I: Satellite

Galaxy Populations Around Eight Milky Way Analogs. The Astrophys. J. 847, 1-21.

Geha, M., Wechsler, R.H., Bernstein, R., et al. 2017. The SAGA Survey.

Retrieved from http://sagasurvey.org

14 Yale Scientific Magazine December 2017 www.yalescientific.org


the genes




The BRCA1 gene has been studied

for over two decades due

to its relationship with cancer

growth, with researchers hoping

to elucidate the processes and mechanisms

of BRCA1 in order to effectively

create cancer treatments. On the surface,

we can only observe the physical symptoms

of cancers affecting millions every

year. Delve one step deeper within the

body, and it becomes clear how the growth

of malignant cancer tumors has severe

weakening effects on every bodily system,

from the immune system to other organ

systems. Zoom one final step deeper,

and the root cause is revealed: the genes

we are born with are intricate yet delicate

structures that can be impacted by the environment

or through its own replication

and functions. It is these genes and their

mutations that greatly affect one’s chances

of rampant cancerous growth. One of the

genes that has been identified as a culprit

in such tumor growth and excessive cell

replication is BRCA1.

Over the last twenty-five years alone,

since the BRCA1 gene was discovered,

about 70 million women have been diagnosed

with breast cancer and ovarian cancer.

The BRCA genes have been identified

as significant factors in the role of cancer

growth, but scientists have never been able

to explain exactly why and. It’s been over

two decades—the number of people who

are affected by cancer is increasing and our

time is dwindling.

Fortunately, researchers in the Sung Lab

at Yale, led by Patrick Sung and Weixing

Zhao, have tackled the problem by developing

their own system of protocol to discover

the function of BRCA1 and its interaction

with other genes in the role of

tumor expression. Despite failures in other

labs for years, the Sung lab was certain

that given the right amount of experience,

time, and careful work with the genes and

proteins of interest, they would be able to

build upon previous research to further

study the elusive gene in a novel way.

The Mysterious BRCA1 Gene

BRCA1 is a gene that produces proteins

that prevent cells from multiplying uncontrollably—a

process responsible for eventually

forming a tumor. Although the gene

has been studied extensively over the last

two decades, it has remained a mystery exactly

which proteins BRCA1 is responsible

for expressing and how it interacts with


December 2017

Yale Scientific Magazine





►Engagement of the BRCA1-BARD1 complex in homologous DNA pairing. In this analogy, the lasso is BRCA1(red)-BARD1(green), the cowboy

is the recombinase RAD51, the large horse is homologous DNA, and the small horse is single-stranded DNA resected from double strand breaks

(DSBs). Caption courtesy of the Sung Lab.

other genes like BARD1. We do know that

the protein made by BRCA1 is involved in

a process called DNA repair, in which it interacts

with other molecules to find damage

within a molecule of DNA and then repair

it. This process is critical to normal cell

function because, when mutations arise,

whether accidentally or through environmental

factors, our bodies require a mechanism

to fix the errors in DNA before the

DNA can be used to produce flawed or unwanted

proteins. In normal humans, there

will be two copies of the functional BRCA1

gene present—one from the mother and

another from the father. As accumulation

of natural mutations or environmental factors

such as radiation from external agents

constantly damage DNA, one or both of the

copies of the gene that coordinates repair

may have mutations or be destroyed. If this

occurs, it is very likely that the DNA repair

mechanism to suppress tumor growth will

be unable to function normally, and there is

a high likelihood of cancer arising.

Among people who inherit just one functioning

copy of the BRCA gene, chances are

that over the years, the functioning gene

will be lost due to environmental damage,

and being devoid of the remaining functional

BRCA gene can eventually lead to

cancer. Mutations in both of the BRCA

genes, called BRCA1and BRCA2, are associated

with all forms of cancer but are

most strongly linked to breast and ovarian

cancer. While it is still a debate why mutations

in these genes primarily affect these

two types of cancers, some believe that

gene expression-related stress is higher in

cells where breast cancer originates. Estrogen-responsive

genes, such as the ones in

breast and ovary tissue, are therefore more


16 Yale Scientific Magazine December 2017 www.yalescientific.org



Solving the Mystery

BRCA1 has been a mystery for so long

in part because the protein encoded by the

BRCA1 gene is large and complex—with

many components that make it difficult to

work with when trying to avoid denaturing.

The first main challenge in their research was

purifying the protein itself. Proteins, in comparison

with other macromolecules such as

carbohydrates, are much more unstable due

to their various components and ability to

denature, or become inactive, in suboptimal

conditions. Sung says it took several years

of experience to finally design a method to

not only express a very large protein but also

work with the proteins without rendering it

inactive. The researchers working with the

protein had to work quickly and gently with

the delicate proteins in a room with a controlled

temperature in order to preserve the

proteins in their functioning state. Leaving

the protein in a high or low temperature environment

or leaving it out for longer than

about half an hour could denature it to the

point where it could no longer be studied.

Their novel approach allowed them to express

thousand-fold the amount of protein

that was previously possible.

After overcoming this obstacle, the team

was set on further studying the proteins. But

there was still one missing piece to the puzzle

– the BRCA-BARD1 complex required a

helping hand in performing their DNA repair


The team hypothesized that the BRCA1-

BARD1 complex works with an enzyme

called Rad51 because they observed certain

properties in protein factors that suggested

a cooperation with Rad51. To test their

hypothesis, they purposely induced DNA

damage in BRCA1 and then placed purified

elements in a test tube to determine whether

the DNA repair system worked. If the DNA

repair mechanism was successful, then that

proved their hypothesis that Rad51 indeed

was the enzyme that cooperated with the

complex to carry out DNA repair.

They were able to conclude that Rad51

recognized the damaged DNA and paired

it up with an undamaged molecule of DNA

to initiate the DNA repair reaction. Furthermore,

the BRCA1-BARD1 complex is essential

to the DNA repair reaction—when the

complex was unable to form, the repair did

not take place, and mutations affecting either

BRCA1 or BARD1 decreased the effectiveness

of repair.


►Dr. Patrick Sung (right), and associate

researcher Dr. Youngho Kwon (left).

Cancer Treatment’s Bright Future

Patrick Sung said that his passion for research

originated in his intellectual curiosity

and realization as a college student that

cancer was a huge problem that needed to

be cured. His ultimate goal is to develop

drugs that target specific known pathways

to treat cancer, and despite the large strides

this recent paper represents in the field, his

work is far from done. After the discovery

of the cooperation between BRCA1,

BARD1, and the Rad51 enzyme, it still remains

a question how BRCA1 and BRCA2

function together. BRCA2 is also a part of

the complex and plays a definite role in the

DNA repair mechanism as well, but it is not

as clearly understood as BRCA1. With their

novel approach to successful protein purification,

these researchers hope to reconstitute

the larger complex including BRCA2

and determine its relation to cancer formation.

Moreover, they are interested in understanding

how mutations work so that

they can find a basis for using compounds

in cancer treatment.

While many questions remain targets of

Sung’s continued research, it is likely that

both the biological discovery and technical

contribution to the protein purification

process will lead to progress in treating

cancers. Now that researchers know how

the protein factors of BRCA1 function,

they can test it in combination with other

genes to see if they can sensitize cancer

cells to available cancer drugs and determine

the efficacy of those drugs—a process

that would help physicians optimize their

prescriptions for their treatments. On the

other hand, they can also use their knowledge

of how the genes bind and function

to develop new compounds that can regulate

DNA repair processes and eventually

be used in preventative cancer drugs. In

the future, the scientists would like to fully

understand the pathways of BRCA genes to

the point where, by studying an individual’s

genes, they can advise the patient about

how likely it is that they will have cancer

and when they might be most susceptible

to cancer so that they may plan their futures


The fight against cancer is well and alive,

as researchers around the world make

strides towards treatments and preventions.

As the Sung Lab passionately scrapes

away the mysteries of BRCA1, we can be

hopeful that we are well on our way towards

answers for curing cancer.



LESLIE SIM is a first year in Jonathan Edwards College at Yale University

interested in cancer research and biophysics. She enjoys fencing, food

photography, and exploring New Haven streets aside from being a writer for

the Yale Scientific.

THE AUTHOR WOULD LIKE TO THANK the Sung Lab at Yale and would

like to thank, in particular, Professor Patrick Sung, Dr. Weixing Zhao, and

Dr. Youngho Kwon for sharing their knowledge with me in interviews and

expressing enthusiasm about cancer research.


Zhao, Weixing et al. “BRCA1-BARD1 promotes RAD51-mediated homologous

DNA pairing.” Nature, vol. 550, no. 360, 4 October 2017, pp. 360-365.


December 2017

Yale Scientific Magazine


Studying the Few to Serve the Many

By Sunnie Liu || Art by Lisa Wu


Yale Scientific Magazine December 2017

The ultimate goal is to provide the greatest

amount of happiness for the greatest number

of people, according to philosopher Jeremy

Bentham.1 Take the U.S. government for example:

it awards grants to scientific research

that provides the most benefits for the maximum

number of people.

As a result, scientific research on disease in

America usually centers around the most common

health issues. The National Institute of

Health reports that the three diseases that received

the most federal funding in 2016 were:

cancer, cardiovascular disease, and HIV/AIDS,

which affect patient populations in the hundreds

of thousands. However, researchers like

Yale professor Dr. Pramod Mistry are studying

uncommon diseases to help underserved patients

with rare health problems.

He combined his work on the rare Gaucher

disease with the Chandra neurology laboratory’s

work on the much more common Parkinson’s

disease, a neurodegenerative disorder that

affects movement. In a recent paper in The Journal

of Neuroscience, this joint project, led by Yale

graduate student Yumiko Taguchi, showed that

the mutations that predispose patients to Parkinson’s

disease are the same mutations responsible

for Gaucher disease. For the first time,

the scientists pinpointed the common mechanism

linking Parkinson’s and Gaucher disease,

setting the foundation for potential new treatments

for Parkinson’s disease that target proteins

directly associated with the pathway.

Underserved patients

While learning about health problems that

affect a large part of the population is certainly

important, Mistry always had an interest in rare

diseases. “At a very human level, I was touched

by how underserved these patients were by the

medical profession,” explained Dr. Mistry.

His passion for helping the underserved patients

with rare diseases led him to study Gaucher

disease—a genetic disorder caused by mutations

in a gene called GBA. These mutations

reduce or eliminate the ability of the enzyme

to break down certain fatty molecules, also

known as lipids, leading to the accumulation

of lipids at toxic levels within cells, damaging

tissues and organs.

Over the years, Mistry encountered a number

of case of patients with Gaucher disease who

also developed Parkinson’s disease. Mistry partnered

with the Chandra lab to study the biology

underlying this correlation. “It was known that

mutations in GBA are the most common risk

factor in developing Parkinson’s disease, but we

now wanted to determine the molecular mechanisms,”

stated Taguchi. The researchers hoped

that to learn more about the relationship between

Gaucher and Parkinson’s disease at a molecular

level, and, by extension, discover potential

targets for treating Parkinson’s disease.

Behind the scenes of Parkinson’s disease

In order to understand the correlation between

Parkinson’s and Gaucher disease, one

must first understand how Parkinson’s develops.

Parkinson’s disease is characterized

by the formation of Lewy bodies, abnormal

clumps of protein that develop inside nerve

cells. Aggregation of the protein α-synuclein

comprises the majority of Lewy bodies, so

mutations in the gene that encodes α-synuclein

lead to Parkinson’s disease.

Although mutations in the gene that encodes

α-synuclein are the direct cause of Parkinson’s,

there are particular risk factors that make these

mutations more likely to happen. Normally,

people have two copies of the gene that creates

this protein. If someone has a mutation in only

one copy, they won’t show symptoms because

the other copy of the gene can make enough

GCase1 protein for normal human function.

However, if someone has Gaucher disease, they





►Yumiko Taguchi, the Yale graduate student

who led the effort on this research project.

have a mutation in both copies of the gene, so

they cannot generate sufficient GCase1 protein.

Interestingly, both patients with a mutation

in only one copy of the gene and patients with

mutations in both copies—Gacuher disease patients—are

more susceptible to Parkinson’s disease.

Those with just one mutated copy of the

gene have a 5-fold increased risk, and those with

two mutated copies have an even higher risk at

20-fold. The scientists wondered how GCase1

mutations might give rise to Parkinson’s disease.

GCase1 protein plays a key role not only

in Parkinson’s, but also in Gaucher disease.

In patients with Gaucher disease, the protein

does not break down a particular complex

lipid GlcCer into the normal simple lipid

products, so both the original and produced

lipids build up. The accumulation of these lipids

characterizes Gaucher disease. Thus, the

researchers proposed that the original complex

lipid GlcCer may contribute to the development

of Parkinson’s disease.

Since mutations that encode α-synuclein

and Gaucher disease both correlate with

Parkinson’s disease, the scientists wanted to

study the relationship, if any, between α-synuclein

and Gaucher disease. A test tube study

showed that the lipids accumulating in Gaucher

disease accelerate the build-up of α-synuclein.

The findings also pinpointed the two

lipids, GlcSph and Sph, that promote more

α-synuclein aggregation than any other lipids

in human cells and neurons.

Justin Abbasi, an undergraduate Yale student

who worked on this research project, summarized

the results: “The proposed mechanism

was really exciting to think about because it

made sense: the lipids build-up caused by Gaucher

disease leads to a protein build-up that

characterize Parkinson’s disease.

After the scientists determined the link between

Parkinson’s disease and the lipids associated

with Gaucher disease, they decided to test

how Gaucher disease mutations affected the

manifestation of Parkinson’s disease. This time,

however, they wanted to conduct the experiments

on mouse models instead of in test tubes.

Relationship status: It’s complicated

The researchers were curious about how

the abnormal breakdown of lipids seen in

Gaucher disease impacted Parkinson’s disease,

so they looked at the lipid levels in the

brains of young mice with Parkinson’s disease.

The scientists discovered that the accumulation

of the lipid GlcSph at concentrations

seen in Gaucher disease produces an

increased amount of the protein α-synuclein.

In addition, the researchers noticed that

as the concentration of GlcSph increased, its

effect on α-synuclein aggregation increased.

These two findings suggest that the accumulation

of GlcSph may exacerbate the aggregation

of α-synuclein in the brain.

Another relationship studied was that of

the accumulation of lipids in the brain and

the mortality of mice with Parkinson’s disease.

The data showed that the mice with Parkinson’s

disease died prematurely, implying that

the mutations in the GBA gene accelerated the

development of Parkinson’s disease. The scientists

also found that the mice who died prematurely

had five times as much of the protein GlcCer

as normal, suggesting a strong correlation

between Parkinson’s disease-related morbidity

and increased lipid levels in the brain.

Connecting these two ideas, the scientists

concluded that for mice with Parkinson’s disease,

α-synuclein aggregated in regions where

GlcCer had built up.

There is no I in team

“Unfortunately, there is no cure to Parkinson’s

disease. You can relieve the symptoms, but that’s

it,” lamented Yumi. However, this new study

provides hope for patients suffering with Parkinson’s

disease: the scientists were able to pinpoint

specific enzymes in the metabolic pathway

that lead to the form of Parkinson’s disease

that stems from mutated GBA genes. Out of all

the various lipids that accumulate due to Gaucher

disease, the researchers found that the

build-up of GlcSph caused the biggest increase

in the risk of developing Parkinson’s disease because

GlcSph accelerated α-synuclein aggregation

the most. Thus, targeting the enzymes involved

with GlcSph offers a potential treatment

for Parkinson’s disease. The data pointed to two

particular enzymes, ASAH1 and glucocerebrosidase

2 (GBA2), as the most promising targets

for treating Parkinson’s disease.

None of these findings would have been

possible without the teamwork between Mistry,

with his Gaucher disease expertise, and the

Chandra Lab, with its neurology expertise. This

case is one of the many important interdisciplinary

science research projects changing the

way we understand disease. Mistry supports

interdisciplinary research as a way for different

branches of knowledge to converge in discovery.

“Any meaningful science now is team science.

The more collaborations you do, the better and

more meaningful your results are going to be,”

asserted Mistry.

Not-so-random mutations



SUNNIE LIU is a first-year prospective art and history of science, medicine, and public

health double major on the pre-med track in Morse College. She writes, photographs,

designs, and illustrates for the Yale Scientific Magazine and volunteers to teach

science and mental health to students in New Haven.

THE AUTHOR WOULD LIKE TO THANK Yumiko Taguchi, Justin Abbasi, Dr.

Sreeganga Chandra, and Dr. Pramond Mistry for their time and for their enthusiasm

about their research.


Neudorfer, O., N. Giladi, D. Elstein, A. Abrahamov, T. Turezkite, E. Aghai, A. Reches,

B. Bembi, and A. Zimran. “Occurrence of Parkinson’s Syndrome in Type 1 Gaucher

Disease.” QJM 89, no. 9 (September 01, 1996): 691-94. Accessed October 20, 2017.



December 2017

Yale Scientific Magazine



evolutionary biology





The head is arguably one of the most distinct features of vertebrates. Sensory organs accumulated into a mass at the

front of the body over the course of evolution have now become a seminal feature of evolution. Protecting this vital

organ is the skull, a bony structure that must closely encase the brain throughout its entire development—from embryo

to adult. It seems only natural for the skull and brain to be closely connected to each other throughout development.

How can two structures evolve as one entity?

Recently, researchers at Yale formally

mapped out this relationship between reptile

and bird brain and skull roof development

for the first time. “Mammals tend to

be more popular to study in developmental

biology because of their complexity compared

to lower vertebrates like reptiles,” said

Bhart-Anjan Bhullar ‘05, assistant professor

of geology and geophysics at Yale. “But,

because of the large size of mammalian

brains, some fundamental structural relationships

can become obscured.” In human

embryos, for instance, the forebrain rapidly

grows over smaller parts of the brain in

the back of the head, making it difficult to

track the relationship between the skull and

brain during development. Reptiles and

birds, on the other hand, have a clearer regions

of the brain that correspond to certain

regions of the skull, making it easier to

track how the skull forms over parts of the

brain. Through combined approaches in

fossils research and developmental biology,

researchers have been able to show for the

first time that the growth and evolution of

the brain has also triggered corresponding

changes in structure and shape of the skull

for millions of years.

Separate but together

In order to understand how the brain

and skull work together, the fossil record

can help distinguish how skull is separated

into different parts that correspond

to different parts of the brain. “The brain

has three partitions in all vertebrates: the

forebrain, midbrain, and hindbrain,” said

Matteo Fabbri, graduate student and lead

author of the published paper. “These partitions

enable embryonic cells to differentiate

into certain bones.” Fabbri and others

at the Bhullar Lab used 3D morphometric

analyses, which visualized patterns of

variation in the brain and skull into different

groupings based on shared qualities, to

examine the skull-morphology and deep

history of the brains of Reptilia and Aves.

“The forebrain will signal to the frontal,

the midbrain signal to the parietal, and the

posterior brain regions will signal to the

back of the skull,” said Fabbri. The presence

of this partition, present in mammals

and reptiles alike, means that it has major

implications for the morphology of the

skull and how it evolves with these parts of

the brain over time.

The research team also examined different

stages of the embryo of various reptiles

by taking eggs at different stages of incubation,

then looking inside of the shell to examine

what the embryo looked like that that

moment. This close examination enabled the

Bhullar Lab to closely study the link between

brain and roofing bones of the skull in early

development. “Logic in developmental biology

is very different from how we think with

the fossil record, but both have the same aim:

to understand why a reptile is like this and a

bird is like this; they are simply complementary

ways of approaching the question.” said

Fabbri. While the fossil record has long been

used to frame the evolutionary relationship

based on morphological differences at

a macro-level, comparative embryology allows

for the developmental level of relation

to be addressed in evolution. The Bhullar

Lab also used CT scanning—which combines

many X-ray measurements to create

an cross-sectional image of an object without

cutting into it—to examine the bone-tobrain

relationship in embryos for the first

time. Despite the physical differences of an

alligator, lizard, and modern-day chicken,

this technology simultaneously visualized

20 Yale Scientific Magazine December 2017 www.yalescientific.org

evolutionary biology


and compared their developing brains and

skull roofs, revealing that they all share the

same developmental pattern.

All three taxa showed direct, one-to-one

correspondence between the developing

forebrain and midbrain with the earliest

stage of development of the frontal and parietal

(roof and sides) bone areas of the skull.

For every degree of development by the

brain, the skull develops to the same extent.

This one-to-one correspondence in embryos

between major parts of the brain and early

skull-roof elements’ developments shows

that the nature of the relationship between

the brain and skull shifts during avian lineage

evolution. Previous studies assumed

that the avian frontal had a fused origin that

caused the resulting shift in avian skull-roof

element identity. These findings collectively

support the notion that the brain is important

in patterning the skull roof.

Not only did Fabbri and the Bhullar Lab

find that there was there a shift in morphology

and relative size to skull from reptiles to birds,

but also in allometry of the brain and skull.

Allometry is the proportional change relative

to body size—specifically the brain and skull

in this case. In this case, there was negative allometry

between the brain and skull during

development of reptiles, meaning that the

brain is relatively large in early developmental

stages, then becomes smaller with respect to

the skull during growth. Birds, on the other

hand, exhibit positive allometry with a large

brain at the hatching stage relative to the skull;

the brain continues to expand during development

into adulthood. “This also shows that

brains in Aves are peramorphic,” Fabbri said,

meaning that although birds retain juvenile

cranial characters observed in dinosaurs and

other reptiles, at the same time, they also exhibit

positive allometry in brain development.

Such differences in development also cause

the evolutionary differences between birds

and reptiles to become more pronounced in

the tree of life.

A collaborative effort

Combining the developmental research

approach with the fossil research approach

could be difficult at times. “We needed to

create comprehensive and inclusive data, but

also needed to be careful.” said Fabbri. “It can

be easy to misinterpret data in the direction

that you were going for.” Nevertheless, after

many correlation tests, the statistical support

was strong behind the embryo’s one-to-one

correspondence between skull and brain development,

showing their co-developmental

relationship. While the fossil record is useful

for examining morphological similarities

and differences across species, it leaves out

gaps in comparative morphology and can

sometimes lead to mistakes in research. This

research’s use of both comparative embryology

and the fossil record more broadly serves

as a reminder to interpret developmental

data within a phylogenetic framework by

fossil records or comparative morphology to

determine homology as a whole.

Moving forward

Officially recognizing the link between the

skull and brain patterning in reptiles and

birds is a significant step in understanding


►Coloring of skull patterning in a chicken skull. Pink represents the frontal skull area, green

represents the parietal skull area, and white represents neurocranial skull area.

how certain morphologies have developed

in reptiles and birds. However, the fact that

bird brains continue to grow further over the

course of their lifetimes compared to other

reptile brains may be due to bird-specific

adaptations such as flight. The research also

represents a larger statement about evolution

itself. “Ultimately, this shows that evolution

is simple and more elegant than it seems.”

Bhullar said. “Now that we have this mapped

out, we better know where to look for gene

expression responsible for these changes.”

The next stage in research may seem more

complicated with a new lens at the genetic

level, but the combination of fossil records

and developmental biology methods and

spirit of collaboration in asking these big

questions are sure to lead to even bigger answers

in the future.



SARAH ADAMS is a prospective Ecology & Evolutionary Biology major in

Morse College ‘20.

THE AUTHOR WOULD LIKE TO THANK Matteo Fabbri and Professor

Anjan Bhullar for sharing their time for this article.


Fabbri, Matteo, et al. “The skull roof tracks the brain during the evolution

and development of reptiles including birds.” Nature Ecology & Evolution,

vol. 1, no. 10, Nov. 2017, pp. 1543–1550., doi:10.1038/s41559-017-0288-2.


December 2017

Yale Scientific Magazine



cell biology



Specialized immune

cells as targets for

metabolism in aging



now possible with specialized immune cells

by Charlie Musoff || art by Sunnie Liu

22 Yale Scientific Magazine December 2017 www.yalescientific.org

cell biology


Areceding hairline, a wrinkly forehead, and a saggy butt are considered undesirable

hallmarks of aging, according to representations in popular media. When people

think about anti-aging, they usually think about reversing this type of surface-level effect.

Everyone has seen beauty campaigns promising to tighten one’s skin or prevent balding,

but the larger causes and effects of aging go far beyond the symptoms in one’s appearance.

While it cannot be argued that the dramatic

increase in the human lifespan over the past

five hundred years reflects positive advancements

in medicine, hygiene, and other health

systems, a longer life comes with an increased

risk of chronic disease. Age is the biggest risk

factor for every chronic disease we know of,

including cancer, cardiovascular disease, and

neurodegeneration, but three different specialists

treat each one. People are not getting

older in a healthy way in large part because

modern medicine does not treat aging in a

disease in and of itself.

Professor Vishwa Deep Dixit and post-doctorate

fellow Christina Camell of the Yale

School of Medicine took up this challenge

and worked to understand aging and its effects

together as one connected disease. They

focused on inflammation, the body’s response

to wound or injury, as a process known to

be a primary trigger of age-related disease.

While in young people, an immune response

will respond to infection and then subside,

in the elderly these patterns of inflammation

never abate, which causes stress and dysfunction.

Dixit and Camell drew a link between

this inflammation and the fat accumulation

also characteristic of aging. The nexus of this

connection lies in macrophages, which are

specialized immune cells. The researchers

found that a class of hormones called catecholamines

directly communicates with a

previously undiscovered subset of macrophages

called nerve-associated macrophages,

which use the nerves to promote lipolysis, or

fat breakdown. Sustained inflammation in

aging increases concentrations of proteins

that degrade these catecholamines, which,

in turn, prevent lipolysis. In other words, as

the mice they used aged, an inability to clear

inflammation decreased catecholamine levels,

which resulted in fat accumulation. This

research implicates crosstalk between the

immune, nervous, and metabolic systems in

the disease of aging, which may provide new

avenues for research to promote wellness in

the elderly.

The deficit

To understand the immune system’s role in

aging and lipolysis, Camell and Dixit initially

needed to flesh out the intersection between

these two processes and the role catecholamines

played in them. Two-year-old mice,

the equivalent of 65-year-old humans, were

shown to release less fat from their adipose

tissue, or fat reserves, than did young ones.

Surprisingly, when the aged mice were given

catecholamines, their rate of lipolysis and

consequent fat release returned to normal,

that is to say that aged fat acted like young fat

when given catecholamines. When cells that

store fat called adipocytes were taken from

these aged mice and grown alongside macrophages,

however, the bounce-back in lipolysis

was no longer observed. Conversely, the addition

of young macrophages to old fat restored

lipolysis. These results were a first clue: catecholamines

promote lipolysis, but something

about aged macrophages specifically reduces

this breakdown of fat. The first major finding,

therefore, was that macrophages in the adipose

tissue control the decrease in lipolysis

observed in aging.

The next step was to figure out the specific

mechanism by which this deficit in fat breakdown

occurs. The researchers analyzed gene

expression in aged macrophages and found

that they express more genes implicated in

catecholamine metabolism than do young

ones, which solidified the link between the

age of the macrophages and their ability to

facilitate lipolysis with catecholamines. One

protein associated with both aging and inflammation

is NLRP3, which forms part of

a larger complex called the inflammasome.

Dixit and Camell found that the activation of

the NLRP3 inflammasome prevented the release

of fats from adipose tissue. On the other

hand, when the researchers engineered mice

without the gene responsible for the production

of NLRP3, they were able to break down

fat normally even as they aged.


The researchers wanted to see if they could

uncover an underlying biological mechanism

that would explain these observations. To

accomplish this goal, they performed RNA

sequencing analysis, which gives a complete

picture of gene expression, and saw that the set

of genes responsible for catecholamine degradation

in aging macrophages was dependent

on NLRP3. Sustained NLRP3 inflammasome

activation—sustained inflammation—thus,

seemed likely to shift the gene expression

profile of macrophages towards the aged one.

A gene called GDF3 that controls fat accumulation

and showed the strongest positive

correlation with aging was reduced down to

the level of young mice when NLRP3 was

knocked out, which corroborates this evidence.

The NLRP3 knockout also showed

restored-to-normal levels of genes implicated

in fat breakdown and catecholamines’ proper

functioning. On the flip side, this result

indicated that an increase in NLRP3 and its

resultant inflammation in aged macrophages

promoted the degradation of catecholamines

that results in reduced lipolysis.

To visualize the location of macrophages

relative to catecholamines, the research team

used reporter mice, which are mice specially

engineered to have fluorescent proteins

in specific cell types. Using these markers,

Camell was surprised to find macrophages

in a pattern never previously observed. “The


December 2017

Yale Scientific Magazine



cell biology

macrophages are actually lining the nerve,”

she said. “They almost look like they’re hugging

it.” This configuration led Camell to conclude

that she had discovered an entirely new

subset of macrophages, termed nerve-associated

macrophages, that represents the intersection

of the nervous, immune, and metabolic

systems. These immune cells directly

access the catecholamines from the nerves,

which allows them to regulate levels of these

hormones in the adipose tissue. Where before,

the exact relationship of the nerve, the

released catecholamine, and the adipocyte

was unclear, now macrophages have been

established as a direct and crucial link. This

immediate connection allows the nerve-associated

macrophages to influence both lipid

metabolism and inflammation, two primary

factors that contribute to aging, via their control

over the concentration of catecholamines

present in the adipose tissue.

Learning how to manipulate this system

was a final step to cement the validity of these

findings. Aged macrohpages were found to

overexpress an enzyme called MAOA that

is implicated in catecholamine degradation,

so the researchers treated aged mice

with a MAOA inhibitor and saw increased

fat breakdown. This result confirms the link

between catecholamine degradation and resistance

to lipolysis in aging. To sum up the

model, when catecholamines are released by

still functional nerves in aged individuals, inflamed

macrophages have excess biological

“machinery” like MAOA that degrades the

catecholamines, so the hormones are broken

down before they can act on the adipocyte to

promote lipolysis. This more complete picture

gives researchers a better comprehension

of the complicated crosstalk between the nervous,

immune, and metabolic systems and

how it influences fat breakdown in aging.

The life in your years

Down the road, an understanding of these

intersecting communication patterns has

far-reaching applications in treatment for aging

in line with its classification as a chronic

disease. The aforementioned class of MAOA

inhibitors is currently used as treatment for

depression, but if research worked to localize

these drugs such that they do not affect

the brain, this therapeutic avenue would

be promising. With lower levels of MAOA

comes higher levels of catecholamines, which

can restore lipolysis in aging individuals. An


►Nerve-associated macrophages, shown in green, seem to hug sympathetic nerves, shown

in white.

alternative target is GDF3, the NLRP3-dependent

protein that inhibits fat breakdown.

While GDF3 is a single upregulated protein

under the overarching control of the NLRP3

inflammasome, NLRP3 itself is required for

fighting off infection, so drugs to block this

protein can increase the risk of certain infections.

Instead, neutralization of GDF3 is an

indirect way to achieve the same goal. If aberrant

inflammation via GDF3 can be prevented,

cells of the adipose tissue will show better

lipolysis. Regardless of the mechanism, these

strategies work to influence the crosstalk

between macrophages and their associated

nerves, which, in turn, influences fat metabolism.

The communication between the nervous,

immune, and metabolic systems that

this research establishes integrates almost

every organ system and so has clear potential

to address the disease of aging as a condition

that impacts all aspects of human health.

When viewed through an even broader

lens, this research is about improving people’s

healthspan, the time during which an individual

is in good health. To clarify the relationship

between catecholamine degradation

and inflammation is to draw the links between

the immune, nervous, and metabolic

systems that, for example, can be implemented

to mitigate neurodegenerative and other

age-related diseases. Ultimately this research

may represent a key to healthier aging. “Our

goal is not to simply increase lifespan,” Dixit

said, “but to add life to the years that exist.”

An understanding of the mechanisms controlling

lipolysis, however narrow of a focus,

can help to achieve this universal ideal: to add

life to your years.



CHARLIE MUSOFF is a sophomore molecular, cellular, and developmental

biology major in Davenport College. Besides being Yale Scientific’s Outreach

Designer, Charlie enjoys running, singing with the Baker’s Dozen, and

teaching with Community Health Educators.

THE AUTHOR WOULD LIKE TO THANK Christina Camell and Professor

Vishwa Deep Dixit for their time and insights.


Pirzgalska, Roksana M, et al. “Sympathetic Neuron-Associated Macrophages

Contribute to Obesity by Importing and Metabolizing Norepinephrine.” Nature

Medicine, 9 Oct. 2017, doi:10.1038/nm.4422.

24 Yale Scientific Magazine December 2017 www.yalescientific.org

materials science



A new microscope images surfaces 5000 times faster



►The second harmonic microscope constructed by the

researchers, used to image a glass capillary.

Many industrial processes rely on chemical reactions occurring

along surfaces, such as the Haber-Bosch process that produces

ammonia on the surface of iron for fertilizer and other industrial

products. It may seem surprising, then, that there are presently

no good ways to observe these reactions on the molecular level in

real-time because of their speed and scale (they occur on a scale

smaller than the width of a human hair).

Earlier this year, however, researchers at the École Polytechnique

Fédérale de Lausanne, a research institution in Lausanne,

Switzerland, constructed and tested of a new type of microscope

that can do just that—look at surface chemistry on the micro-scale

in real-time. Using their microscope, the researchers measured, in

a matter of milliseconds, the variation in chemical properties of

a glass surface over micrometers. Their results were published in

August 2017 in Science.

The first of its kind, this microscope is known as a “wide-field,

structured illumination, second harmonic microscope,” which, as

its name suggests, utilizes a phenomenon called second harmonic

generation (SHG). SHG is a process that allows two photons—

particles of light—to combine under certain conditions, resulting

in a new photon with exactly twice the frequency. This is similar

to how two water droplets, when colliding with suitable orientations

and speeds, can combine to form a droplet with precisely

twice the volume.

For SHG, the new photon forms only when two original photons

interact with a non-centrosymmetric material—a material

without a central point about which the molecules can be reflected.

For example, a pizza in five slices is non-centrosymmetric,

while a pizza in six slices is centrosymmetric. The net number of

photons generated by SHG depends on the orientation of this

non-centrosymmetric material.

This property is what allows the researchers to use SHG in their

microscope. First, to reveal underlying chemical structures of a

glass-water interface, the researchers wetted the surface, causing

water molecules to selectively cluster on areas to which they

were more attracted, akin to how shaking a tray of sand with a

strip of glue collects sand along that strip. Next, the researchers

shined light onto the whole surface, showering it with photons.

Because water molecules are non-centrosymmetric, the amount

of SHG depends on the orientation of the water molecules, which

in turn depends on the surface’s underlying chemical structure.

By measuring the output of SHG photons coming from different

positions on the curved glass surface, the researchers were able to

reconstruct the chemical properties of the different parts of the

surface in 3D.

Since this microscope captures the entire surface all at once, it

captures images more than 5000 times faster than current second

harmonic microscopes. Most importantly, this increase in speed

does not sacrifice image quality. Sylvie Roke, the principle investigator

of the project, was herself pleasantly surprised about the

sensitivity of the microscope. “What I find amazing is that there

are so few oriented water molecules—just one nanometer of oriented

water molecules—and I can see them so brightly,” Roke


The advantages of this new microscope hardly end there. Sapun

H. Parekh of the Max Planck Institute for Polymer Research

in Mainz, Germany, added that this microscope offers the additional

benefit of being operational even without precise control

of the environment—unlike most other methods to study surface

chemistry that require ultrahigh vacuums to operate. One

straightforward application of this microscope could be to improve

the industrial manufacturing of surfaces, such as solar cells.

By examining the surface chemistry of manufactured surfaces in

real-time, we can get immediate feedback on the manufacturing

processes, making its optimization easier and more efficient.

Roke foresees even more exciting applications for the new microscope,

such as imaging biological processes like neurons firing.

“Neurons communicate by electrostatic signals that travel across

the membrane,” Roke said. “What if I could use this method to

[image the] membrane of the neuron while it is signaling to other

neurons, without modifying the neuron?” This would be an impressive

step forward to understanding how neurons function,

since current technologies only allow us to observe neurons by

modifying them.

While there are still some nuances in second harmonic microscopy

that remain to be explicitly addressed, the researchers have

certainly accomplished a proof of concept with the new instrument.

As Parekh puts it, “What they showed is not the end application—it’s

just the beginning.”


December 2017

Yale Scientific Magazine





The neural mechanisms that regulate water consumption


Water is essential for life. Its consumption is so intuitive, you probably

don’t recall the last time you drank up. The body must work

constantly to combat water loss caused by urine production, sweating,

and respiration, most often by inducing water intake. Though

water regulation is an essential process, the brain mechanisms that

govern thirst were unknown until now. “Thirst is an ancient and

extremely powerful motivational signal,” said Will Allen, a graduate

student in the Department of Biology at Stanford, where he and his

colleagues study neural pathways that motivate thirst. Their results

were reported in Science this September.

Animal behaviors, including thirst, are known to be motivated

by two distinct mechanisms. The first is “drive reduction,” whereby

thirsty animals learn to drink to avoid the “aversive state” of thirst.

The second mechanism works the opposite way: thirsty animals

have greater incentive than their satiated counterparts to drink for

the “reward” of satiety. Previous studies suggested that the latter reward

mechanism is more likely in the case of thirst, but could not

provide neural mechanisms to support this hypothesis.

The study at Stanford provided evidence that thirst is an “aversive

internal state” and is actually driven by the first mechanism. “This

study provides a neural implementation of a long-discarded theory

from psychology about how motivational drives produce behavior,”

Allen said. The conclusion was enabled by recently-developed techniques

that allowed researchers to selectively access, activate and

manipulate neurons in the brain.

To identify the specific group of neurons that encode thirst, the

researchers altered the genetic sequences of mice so that cells would

fluoresce in red during thirst. The fluorescence gene is aptly named

tdTomato. By comparing tdTomato fluorescence between water-deprived

and water-satiated mice, they were able to pick out the

cells that had increased activity due to thirst.

The researchers then isolated the tdTomato-positive cells before

using single-cell RNA sequencing to determine individual genetic

expression profiles. Based on these profiles, the researchers identified

two cell types. One of the cell types was concentrated in the median

preoptic nucleus (MnPO) in the hypothalamus region of the

brain. Since the hypothalamus is known to regulate many metabolic

processes, the MnPO neurons were expected to be the primary

motivators of thirst.

The researchers hypothesized that if the MnPO neurons indeed

motivate thirst, then artificially activating them should induce water

consumption. They inserted genetic “switches” into mice MnPO

neurons to turn thirst on and off with a laser beam and a fiber optic

implant. Photoactivation of the neurons in water-satiated animals

induced water consumption, and the rate of water consumption

scaled with frequency of stimulation. Water-deprived mice were

trained to press a lever to obtain water, such that photoactivation of

the neurons induced lever-pressing.

To determine that activity of these neurons causes an aversive

state, two experiments were performed. First, mice were put into

a chamber, one half of which photoactivated the neurons. Mice invariably

learned to avoid that half. In the second experiment, water-deprived

mice were provided a lever that turned off photoactivation.

They learned to vigorously lever-press, even though no

water was provided upon pressing. Moreover, the higher the frequency

of photoactivation, the higher rate of lever-pressing. Their

response indicated that higher levels of MnPO neuron activity are

more aversive, and result in stronger thirst.

Finally, the researchers investigated how MnPO neuron activity

decreases upon water intake. They proposed three mechanisms:

first, that neuron activity decreases due to anticipation of water; second,

that neuron activity decreases as water is consumed; and third,

that neuron activity continues until a certain satiety threshold, after

which it abruptly turns off. Once again, they inserted the tdTomato

fluorescence gene into MnPO neurons, allowing the neurons

to fluoresce with an intensity proportional to their activity. When

mice were allowed to press a lever to obtain water, their MnPO activity

decreased gradually over several minutes, much more slowly

than during free drinking. Once neuron activity reached a minimum,

the mice stopped lever-pressing. This indicated that MnPO

neurons receive quantitative real-time feedback from the body, and

adjust their activity accordingly.

The study shows how MnPO neurons regulate animals’ water-seeking

behavior, improving our understanding of how thirst

is motivated. It remains to be seen whether the alternative reward

mechanism has any role in thirst, how MnPO neurons know when

satiety is achieved, and what makes up the myriad secondary pathways

that enable such a small cluster of cells to elicit a coordinated

response, supporting the survival of animals for hundreds of thousands

of years.


► Thirst is a primordial drive in response to the constant need to

combat water loss.

26 Yale Scientific Magazine December 2017 www.yalescientific.org





Harvesting energy with carbon nanotube yarns


►Carbon nanotubes are a carbon allotrope that exhibit remarkable

electromagnetic and mechanical properties.

Picture a bike ride along the seaside. Your T-shirt has a

built-in heart rate monitor to track your activity. Floating up

from the picturesque water are dozens, maybe hundreds of

balloons that feed into a charging station on the beach, where

you can recharge your phone to take a photo of the incredible

scene. This is the future that Carter Haines, associate research

professor at the University of Texas in Dallas, envisions.

Haines and his collaborators have figured out a way

to turn mechanical energy into electricity with the help of

carbon nanotube yarns.

At the heart of the method is a capacitor. The archetypal

capacitor is called a parallel-plate electrostatic capacitor, and

it consists of a positive and a negative electrode with some dielectric

medium in between. This dielectric is a material that

stores charge well; the electrodes, by contrast, are conductors

through which charge is quickly removed as a current. You

can charge a capacitor to a high voltage and then harvest the

energy inside it at a later time.

“You take a piece of rubber, coat carbon grease on both

sides to get electrodes, and as you stretch and release this

rubber you can change the capacitance and get energy out,”

Haines said. However, the trouble with electrostatic capacitors

is two-fold. First, of course, you have to charge them

up with an electronic circuit to start with. Second, a human

body, with its high conductivity, probably shouldn’t be near,

let alone touching, high voltages.

This is the beauty of electrochemical capacitors. Virtually

all electrochemical capacitors today have electrodes made of

carbon allotropes—different forms of carbon with its atoms

interacting in different ways—with high surface areas. Carbon

nanotubes are one class of such allotropes. First discovered by

Soviet scientists Radushkevich and Lukyanovich in 1952, they

are incredibly strong and stiff, with length-to-diameter ratios

of up to 100 million. They are grown upright in what is called a

forest, then pulled out into fibers and twisted into yarns. “The

nanotubes are no longer in the yarn axis, but are following

helical paths, just as you’d have with any yarn that you twist,”

Haines said. If you continue to twist the yarn under pressure,

it will actually form coils; you’ve probably discovered this phenomenon

while playing with your shoelaces. With the right

amount of tension on the ends of the yarn during the twisting

process, you can get neatly packed coils.

The dielectric in an electrochemical capacitor is an electrolyte,

a solution of charged ions in a liquid. “Because there’s

so much surface area on the surface of the nanotubes, the

ions can just come and hang out on the surface,” Haines said.

“When we compress the yarn, we’re actually getting rid of

surface area.” By pulling one strand (one electrode) and tightening

the twist, the ions on it pack closer together, increasing

the voltage. Since the ions all have the same sign, they repel

each other and are eager to escape. Even a small voltage on

the surface area of the nanotubes will collect a large charge—

much larger than the charge on their conventional parallel

plate counterparts. Thus, electrochemical capacitors have

earned the alternate name of “supercapacitors,” and their low

voltage means no electrocuted humans.

The most interesting application is the potential for embedding

the yarns into clothing. The group has already tracked

breathing, which Haines says is just the beginning. “You can

measure things like pulse, heart rate and all sorts of things

about the way the body is moving just by having different

yarns embedded in the textile,” Haines said. The biggest roadblock

to a commercial-scale use of energy-harvesting yarns is

the production cost of the carbon nanotubes. The search is on

for cheaper alternatives that have the same ability to host ions

from an electrolyte on an easily changeable surface area.

In the lab and in the fabrics, the electrolyte is some kind

of synthetic gel. But it turns out that seawater, with its high

salt concentration, also works well. Haines’ collaborators in

South Korea did indeed attach a balloon to one end of the

yarn and hold the other down to the seabed with a rock.

“They can see the voltage coming out of the yarn as the waves

are moving the balloon around,” Haines said. Harvesting the

mechanical energy of ocean waves has been an open challenge,

and one that these yarns may rise to meet—if scientists

succeed in finding a way to affordably produce them on the

industrial scale.


December 2017

Yale Scientific Magazine


Pesticides, Honey, and Dead Bees

|| global honey contamination with neonicotinoids ||

by Jiyoung Kang

art by Zihao Lin

As the weather gets colder,

most of us love bundling

up with a cup of hot tea

with honey. Not only do

bees provide us with delicious honey,

but they also pollinate about a third of

all food we eat. We admire bees as hard

workers, marvel at their waggle dance,

and thank them for honey and other pollinated

foods. However, their population has

been rapidly declining across the world due to threats

such as habitat loss, disease and pesticide use.

One class of pesticides known to be toxic to pollinators

is the neonicotinoids (termed “neonics”),

the most widely-used class of insecticides.

They affect the bees’ health, interfering

with their metabolism, learning

and growth. They even threaten the

health of queen bees, which can be severely detrimental to colony

population sizes. In a study recently published in Science, a team of

researchers at University of Neuchâtel and the botanical garden of

Neuchâtel found that most honey samples around the world are contaminated

with these dangerous neonics.

The project stemmed from an exhibition on bees organized by the

botanical garden of Neuchâtel in Switzerland. The director came up

with the idea of gathering global honey samples and asked visitors,

friends and colleagues who were travelling to bring back local honey.

Edward Mitchell and Alexandre Aebi, researchers at University of

Neuchâtel, saw the potential to use the university’s analytic capabilities

to do something more with this worldwide collection of honey—and

thus the collaboration began. Because of the controversy about pesticides

and pollinator populations and because of neonics’ wide use and

well-known effects on pollinators, they decided to construct a global

map of honey exposure to neonics.

Over one hundred colleagues, friends and relatives joined forces to

collect honey from every continent except Antarctica. The researchers

then selected and tested almost 200 samples for five different neonics.

Their results were shocking. The pesticides were found in 75% of all

samples, and 45% were contaminated with more than one of the five

tested compounds. The effects of exposure to this “cocktail” are still

not fully understood, but such combinations are suspected to be much

more lethal for bees than individual compounds alone. Additionally,

levels of neonics in nearly half of the samples exceeded the lowest

concentration at which they are known to be harmful to bees. The

detected levels were below the limit for human consumption according

to current EU regulations, although the long-term consequences

of consuming these “safe” honeys are still unknown.

According to the researchers, the significance of their work is several-fold.

“Many people will say that it is not surprising that there are pesticides

in honey, but we put a figure to this; we mapped it out,” Mitchell

said. Although there have been previous studies analyzing the pattern

of neonics and their impact on pollinators, this study is unique in that it

provides a global perspective. It was shocking, even for the researchers,

that such a high percentage of honey samples from all around the world

were contaminated with neonics.

Mitchell also believes that their work generates many new questions.

Although the neonicotinoid levels were below the limit set by regulations

on human consumption, the researchers cannot definitively say that it is

safe to eat contaminated honey. “We still don’t know how consuming

low concentrations of pesticide over a long period of time affects the

human body,” Mitchell said. Plus, more evidence is emerging that neonics

might have detrimental effects not only on non-target invertebrates

but also on vertebrates, which include humans.

This study focused only on a subset of neonics—only five out of the

several hundred pesticide types used throughout the world. “So, there

is this big question mark about what else there is in honey, and not

just in honey but even in every food we eat,” Mitchell said. Although

their research cannot provide the answer, he believes it is important

to continue raising these questions and conducting more research on

the topic. “We should be more cautious about the way we develop and

use these pesticides and look for alternatives in case these pesticides

turn out not to be absolutely essential,” he said. Neonics are used to

coat seeds so that insects that later feed on the plants will be exposed

to the toxic compounds. Therefore, they are used preventively to minimize

future attacks, rather than as a direct response to a specific attack,

which is why Aebi believes that their necessity should be reevaluated.



There have already been cases in Switzerland in which a partial ban

on specific pesticides did not lead to yield losses in crops, contrary to

farmers’ worries.

Aebi has been a beekeeper for 15 years, in addition to being a biologist

and an anthropologist. He has experienced the changes in bee

population and honey first-hand. When the researchers first started


►Alexandre Aebi, one of the researchers behind this study, has

been a beekeeper for 15 years and has witnessed changes in bee

populations first-hand.

the project, they wanted to develop a technique to chemically analyze

the global collection of honey. They needed pure honey for their

protocol, so they could contaminate it with a known concentration of

neonics and calibrate their machines. Aebi recollected how he naively

thought that it would be easy, assuming that his honey was pure. It

turned out that his honey was contaminated with three molecules,

even though he has been taking care of his bees organically. “It is not

easy to keep the bees in purely harmless surroundings, because bees

can travel up to twelve kilometers to collect nectar,” he said. Despite

bans on neonics for certain crops, bees can still travel far away and be

affected by the pesticides in other farms or private gardens.

He has also heard from his beekeeping friends that not long ago, their

queen bees lived for around five years, but now the queens have to be

replaced every two years. When the queens are exposed to neonics,

they lose the ability to store spermatozoids, which decreases their ability

to produce new bees.

As such, the effects of neonics on bees are real and detrimental. The

researchers believe that political actions are crucial to minimize further

damage. A total ban on all neonics is in the works in France, and

partial bans are in effect throughout the EU, although their impacts are

yet unknown. More research must be initiated and funded to assess

such long-term consequences of pesticide exposure and regulations,

and to develop new alternatives and re-analyze the necessity of these

toxic compounds.

As a next step, the researchers would like to create maps for individual

countries or smaller regions, and possibly for different categories

of pesticides such as herbicides and fungicides. Aebi believes that

analyzing changes in wild bees and populations of other organisms

is also important. The researchers envision a future where both crop

yields and the environment are protected, with bees happily and safely

buzzing around, making honey.


December 2017

Yale Scientific Magazine






Hydrothermal seafloor deposits on Mars send us back in time.


The search for the origin of life often leads deep

into the annals of Earth’s geological record. Based

on fossil evidence, scientists believe that early life

may have thrived in a hydrothermal seafloor environment

3.8 billion years ago; however, because

of Earth’s active plate tectonics, most geologic evidence

from this time period has been altered or

overwritten by younger, or more recent, geological

activity. A group of researchers led by Professor

Joseph R. Michalski from the University of

Hong Kong, however, recently uncovered strong

mineral evidence of contemporaneous hydrothermal

activity in the Eridania basin on Mars.

Since Mars and Earth share a similar early history,

these deposits could potentially lend insight

into conditions on early Earth. This research was

published July 2017 in Nature’s Communications.

Earth and Mars both formed about 4.6 billion

years ago, at the same time as the rest of the solar

system. Theoretical models combined with

chemical and geological evidence suggest that

their early environments were very similar; thus,

their early geological records are thought to hold

analogous information. Furthermore, whereas

Earth’s early geological record has been mostly

deformed or destroyed, Mars’ remains largely

pristine because Mars, unlike Earth, no longer

has active plate tectonics.

Earth’s interior is divided into three main layers:

the crust, the mantle, and the core. The crust

is the Earth’s surface, the core is the Earth’s center,

and the mantle is the thick layer of molten rock

in between. The theory of plate tectonics posits

that Earth’s crust is divided into several sections,

or plates, that push and rub against each other to

produce mountains, volcanoes, earthquakes, and

other geological phenomena. These movements

are driven by convection within the mantle, a

process of heat transfer that results in the creation

of a sort of cycling current. This process is

analogous to a pot of water on a stove: the burner

directly heats the water at the bottom of the

pot, causing it to rise. When this water reaches

the top, it loses some of its heat to the air, causing

it to cool and sink back to the bottom, where it

is heated again. This repeated process of heating,

rising, cooling, and then sinking creates a sort of

current inside the pot. The Earth’s mantle undergoes

a similar process, except instead of a stove, it

is heated by the Earth’s core.

One of the consequences of plate tectonics is

the constant recycling of oceanic crust. When

two plates push against each other, one of them

is sometimes pushed beneath the other, causing

it to sink and melt in the mantle. This process,

called subduction, is particularly prevalent in

oceanic crust. As a result, ancient oceanic crust

is often destroyed or altered over time, meaning

that clear geological records documenting the

emergence and early development of life are difficult

to find on Earth.

Geological evidence suggests that Mars may

have once also had plate tectonics; however, due

to its relatively small size, this stopped long ago.

All planets radiate heat, meaning that they slowly

cool over time. Since Mars is much smaller in size

than Earth, it loses heat at a faster rate, similar

to how a cup of tea would cool faster than a pot

of soup. Since plate tectonics depends on convection,

which in turn depends on the presence

of a heat source, this heat loss means that Mars’

plate tectonics eventually shut down. Thus, Mars’

ancient geological record remains relatively undisturbed,

making it a valuable “Rosetta Stone”

for studying environmental conditions on early


The Eridania basin is one of the oldest regions

of Mars’ crust. Previous research has shown that

it is composed of several smaller, connected

sub-basins that were once filled with water to a

depth of up to 1.5 km, making it the site of an

ancient sea. The Eridania basin contained more

water than all other Martian lakes combined, and

it would have had almost three times the volume

of the largest lake on Earth, the Caspian Sea.

Michalski’s group expanded upon these findings

by analyzing Eridania’s mineralogy using

data collected via high-resolution satellite imaging

and infrared spectroscopy. Infrared spectroscopy

uses infrared light, a type of light invisible to

30 Yale Scientific Magazine December 2017 www.yalescientific.org




►The study determined that Eridania’s deposits had a hydrothermal

origin, meaning that they formed as a result of underwater volcanic



►Previous research has shown that the Eridania Basin is composed

of several sub-basins that were filled at most up to the 1,100 m

elevation line. This suggests that the parts of the lake were between

1-1.5 km deep.


►The study used spectral data collected by NASA’s CRISM, an imaging

spectrometer that was built to search for mineralogical evidence of

water on Mars’ surface.

the human eye, to “look” at chemical compounds. This enables

scientists to see minerals in “colors” absents in visible light, allowing

them to identify the minerals. The infrared data used in

the study was collected through NASA’s CRISM (Compact Reconnaissance

Imaging Spectrometer for Mars), an instrument

on the Mars Reconnaissance Orbiter (MRO) that searches for

mineralogical evidence of past water on Mars’ surface. Satellite

images were used to help the researchers to contextualize their

results in terms of the planet’s actual geography to create a better


The researchers discovered that the Eridania basin contained

iron- and magnesium-rich clays. These substances are widespread

across Mars’ surface; however, the specific types and distribution

of clays present were unusual and sometimes matched

better with terrain on Earth’s seafloors than terrain on Mars.

In addition to clays, the researchers also found evidence of

carbonates, silica, and sulfides—compounds all formed through

hydrothermal activity, or underwater volcanism, on Earth. Using

a crater-counting function, the researchers also determined

that the deposits were about 3.8 billion years old, contemporaneous

with the oldest evidence of life on Earth.

Eridania’s clays may have formed through evaporation. However,

this would have resulted in the production of chemical

compounds not present in the deposits, making this hypothesis

unlikely. An alternative explanation for the deposits is air

fall—for instance, wind could have carried ash from a nearby

volcanic eruption into the basin. However, since no deposits of

similar age were found anywhere outside of the basin, this too

is implausible. Thus, the researchers concluded that the deposits

were most likely created in a hydrothermal context. This is

supported by the presence of large volumes of lava on the basin

floor, indicating that significant volcanic activity occurred at

some point during the basin’s history.

The Eridania basin is unique among other sites on Mars in its

ability to illuminate the conditions surrounding the origin of

life on Earth. Not only does it represent an ancient hydrothermal

environment, but it was also active around the same time

early life thrived on Earth. Michalski hopes that future studies

will continue investigating the details of his group’s current results.

He also hopes for a rover visit to the Eridania basin in the

future. “If we can visit it with a rover and obtain some physical

samples of the terrain, we would surely learn a lot about how

life originates, even if we don’t find direct evidence of life,” Michalski



December 2017

Yale Scientific Magazine


FEATURE cell biology


Programing Bacteria to Make Materials

by MINDY LE || art by JASON YANG

In the past few decades, scientists have increasingly delved into

the field of synthetic biology. As its name suggests, synthetic biology

combines the realms of biology and engineering to produce systems

never before seen in nature. Often, these systems are inspired by

what is found in nature, but they proceed a step further by undergoing

“engineering” to become something more beneficial. In the

context of synthetic biology, engineering typically refers to the introduction

of foreign genetic material with “instructions” that tell the

organism of interest what to produce. However, synthetic biology is

not limited to simply expressing a biological product. In fact, scientists

have come up with a number of ways to engineer organisms to

do unexpected, beneficial things. For example, have you ever considered

designing bacteria that act as pressure sensors?

While such a physical device made up of microorganisms seems

difficult to imagine, researchers at Duke University have accomplished

just that. By engineering self-patterning bacteria that can

be printed on permeable, three-dimensional scaffolds, they generated

pressure sensors out of microbes. The sensors are domeshaped

and are made of both organic and inorganic materials,

namely gold nanoparticles applied onto the bacteria.

In a study published in early October, the researchers engineered

a specific strain of Escherichia coli (E. coli), a bacterium commonly

used in biological research, to produce a protein that composes the

pressure sensor. “The main motivation is to demonstrate the following

principle: living cells can be engineered to form self-organized

2D or 3D structures, which in turn can be used to assemble structured

materials with well-defined physical properties,” said Lingchong

You, the head researcher on the study and a biomedical engineering

professor at Duke University.

The team chose to develop pressure sensors based on previous work

at Harvard and MIT, where bacteria were engineered and applied onto

pre-patterned, 2D surfaces to make electrically conductive biofilm

switches that were controlled by an external electrode and supplemented

with inorganic nanoparticles for conductivity. “Pressure sensing

happens to be a function we used to demonstrate the idea above,” You

said. “Our work represents a fundamentally new strategy to assemble

32 Yale Scientific Magazine December 2017 www.yalescientific.org

structured materials with well-defined physical properties.”

To engineer a genetic circuit in E. coli that produced the pressure

sensor’s scaffolding material, the researchers introduced foreign

plasmids into the bacteria. Plasmids are circular pieces of DNA that

carry a set of instructions telling the bacteria what to do. In this experiment,

the foreign plasmids instructed the bacteria to produce a

protein called curli, which acts as the building block to assemble the

pressure sensor’s dome-like structure.

Following plasmid introduction, the researchers laid out a scaffolding

design with a permeable membrane template—outlined using a

modified inkjet printer—underneath growth media. The membrane

provided structural support for both bacterial growth and the later

addition of gold nanoparticles. After constructing the membrane support,

a liquid culture of the bacteria was applied over the membrane.

Individual bacterial colonies grew into the dome-like shapes, which

researchers could control by adjusting the pore size and hydrophobicity

(the extent of water-repulsion) of the membrane.

To complete the pressure sensor, gold nanoparticles were overlaid

onto the bacterial colony domes after the colonies were fixed into

place. The researchers hypothesized that the viscoelasticity—or resistance

to shear stress and distortion—of the organic curli matrix, combined

with the conductivity of the gold nanoparticles, could contribute

to a functional organic-inorganic hybrid pressure sensor.

Indeed, this is what they observed. When two bacterial domes were

moved to face each other and a constant electrical voltage was applied

to the edge of a dome, the contact between both domes allowed electrical

current to flow. One way to visualize this is by imagining that each

bacterial dome is someone’s face. Just like the spark of a first kiss, when

the two bacterial domes make contact, an electrical current is produced.

Importantly, the strength of the current reflected the strength of the

externally applied pressure. After further testing this relationship, both

verifying and modeling the association, the researchers established that

the bacterial domes could act as robust pressure sensors.

The investigation is a key step toward improving our understanding

of how to program spatial patterns in cell populations, a topic

within synthetic biology that has often been neglected. While this

neglect is partially due to the difficulty of modeling spatiotemporal

patterns over just temporal ones, other concerns include the difficulty

of demonstrating such dynamics experimentally. In this investigation,

the researchers not only addressed such concerns but also took a step

beyond previous work by introducing the programming of self-organization.

Here, the engineered bacteria were able to grow into their

desired structure without any pre-patterning.

What do these bacterial pressure sensors hold for the future? “There

are many opportunities and we’re currently pursuing some of these.

We can imagine the generation of hybrid materials with other properties

that can be used for diverse applications, including environmental

cleanup and medicine,” You said.

Additionally, the researchers discussed the possibility of using curli

to form other structures with different inorganic materials introduced.

For example, if the gold nanoparticles were replaced with catalytic

metal nanoparticles, catalytic structures could be built for many chemical

and physical applications. Likewise, the curli protein itself could

be replaced by other organic molecules to produce materials such as

hydrogels. There is also the possibility of using other organisms, such

as yeast, to create different pattern formations.

The future of this technology holds much promise. “I expect that the

research in this direction will need to simultaneously address two related

►An artist’s rendition of nanoparticles in a cell

cell biology



issues. One is to push the limit in terms of the diversity of materials that

can be generated by living cells. The other is to generate specific types of

materials for specific applications,” You added. Moving forward, their

team hopes to expand on this work. “As the next step, we’re focusing

on two directions: the generation of different kinds of spatial patterns,

which remains a fundamental challenge in synthetic biology, and the

implementation of different types of hybrid living materials,” You said.

Here at Yale, researchers at the Yale Microbial Sciences Institute are

also employing synthetic biology to make new materials. One such

scientist is Nikhil Malvankar, an assistant professor in the Yale Department

of Molecular Biophysics & Biochemistry. Malvankar’s laboratory

focuses on engineering soil bacteria that produce pili, a naturally conductive,

filamentous protein that functions similarly to copper wires.

His group aims to uncover the mechanisms of electron movement

within these filaments, which act as nanoscale “wires” with tunable

conductivity, to better understand how this system works at the molecular

level and then to apply this knowledge to improve other bacterial

systems. “The long term goals are to use synthetic biology for designing

biomaterials and bioelectronics devices that will complement

and extend current semiconducting technology,” Malvankar said.

Regarding the growing potential of synthetic biology, Malvankar

highlights critical points to consider when working with microorganisms.

“Bacteria are very adaptable organisms and employ multiple

components and redundant pathways for cellular processes.

Furthermore, bacteria can only function in limited environmental

conditions such as physiological pH and aqueous environment,”

Malvankar said. He also provided ideas for improving the bacterial

pressure sensors. “In the future, it should be feasible to use living

cells rather than fixed cells and also avoid expensive and toxic gold

nanoparticles and use all-organic, biological systems.”

With all of these applications and more, the future of synthetic

biology is very exciting. “In the current state of synthetic biology

and bioengineering, one fundamental question is what things we

can actually fabricate using living things. I hope to see different

examples emerging from the community, which can further stimulate

our imagination,” You said.


December 2017

Yale Scientific Magazine





Understanding forest regrowth is crucial to predicting and

mitigating environmental damage, and with over half of the word’s

tropical forests currently recovering from human land use, insight

into forest regrowth mechanisms is more important than ever.

To accurately model and fully leverage the potential of regrowing

forests to act as carbon sinks for climate-changing atmospheric

carbon dioxide, we must comprehend the mechanisms that augment

and limit the growth rates of these recovering forests.

Trees need a variety of resources to grow, and their growth is limited

by the scarcest of these resources. Often, this limiting resource is

nitrogen. Nitrogen becomes available to plants when nitrogenfixing

bacteria on a host plant’s roots convert nitrogen in the air into

a plant-usable form available to both the host (called a nitrogenfixing

plant) and its neighbors. This has led many researchers who

study forest regrowth to posit that more nitrogen-fixing trees leads

to more overall forest growth. However, a team of researchers

from Columbia University, the University of Connecticut, and

Rice University recently called this conclusion into question. They

found that in moist Costa Rican tropical forests, areas with more

nitrogen-fixing trees actually had a lower growth rate than did those


►The primary nitrogen-fixing tree examined was Pentaclethra macroloba,

a tree native to moist tropical forests such as those noted in the study.

with fewer nitrogen-fixing trees. The results of this study call for a

reevaluation of the influence of nitrogen fixers on the forest around


In order to test whether nitrogen fixers augmented forest growth,

the researchers searched for connections between the presence

of nitrogen-fixing trees and growth of surrounding trees. In onehectare

plot areas, they compared the number of nitrogen-fixing

trees with both annual tree growth and the growth of the fixer’s

neighboring trees. Surprisingly, in both cases, the researchers

observed a negative trend that suggested that more nitrogen fixers

lead to slower forest growth.

The researchers proposed several possible explanations for these

unexpected results. While nitrogen-fixing trees provide usable

nitrogen to the trees around them, they may crowd out their nonfixing

neighbors. Fixing-trees have high growth and survival rates,

as well as high nutrient demands. Their resource consumption and

the shade they produce may inhibit neighboring trees from growing.

Additionally, nitrogen may not be the limiting factor in the growth

of these neighboring trees—in fact, the limiting resource may be

something that the presence of nitrogen-fixing trees is making even


The results from this research run counter to several similar

studies. Two studies on regenerating moist tropical forests in Brazil

and Panama found that the number of nitrogen-fixing trees was

positively correlated with total biomass accumulation. Why do the

results conflict? A difference in the ages of forests and genera of trees

may contribute to the disparity, but the researchers believe that the

disparity is more likely due to differences in baseline soil nutrient

availability between the sites analyzed in the studies.

Benton Taylor, PhD student at Columbia University and first

author of the paper, highlighted the implications of the study for

Earth systems modelers and their assumptions on the effect of

nitrogen-fixing trees on growth and atmospheric carbon dioxide

levels. “If modelers assume that places with high nitrogen-fixer

abundances will have high nitrogen inputs and, thus, have high rates

of growth and carbon sequestration, the results of their models may

be misleading,” Taylor said. He further noted that, although several

pieces of evidence suggest that the study’s results may be typical,

the questions of when and through what ecological factors nitrogen

fixers have an effect on forest growth remain unanswered. These are

the questions Taylor plans to pursue.

Forest regrowth is having and will continue to have a pivotal effect

on the world’s climate. Climate predictions and climate mitigation

both hinge on a better understanding of forest regrowth and

the mechanisms through which it may be augmented. The nowprevalent

regrowth of tropical forests ought to serve as a focus for

curbing climate change—but it’s clear that fixing nitrogen won’t

necessarily fix everything.

34 Yale Scientific Magazine December 2017 www.yalescientific.org



Optimal Leaps in Optimizing Fat Burn


Society’s embrace of dietary interventions and increased

physical activity ensues to relieve obesity as a global health

threat, but such interventions can only go so far. Dieting and

exercise have seemingly helped athletes and those who wish

to shed a few extra pounds, but the market lacks an affordable,

accessible and accurate technology to monitor progress in

body fat loss. Consider bringing a ten-thousand-dollar mass

spectrometer—the necessary machinery to collect fat loss

data, comparable in size to an office printer—to the gym.

It may seem extreme to go to such lengths to measure fat

burning, but until now, there was little else to rely on.

New research curtails these concerns. Investigators at ETH

Zurich and the University Hospital Zurich have recently

developed a real-time breath acetone sensor to detect fat

burning through a person’s exhalations during physical

exercise. Andreas Güntner, a co-author of the study and a

postdoctoral researcher in the lab run by professor Sotiris

Pratsinis, explains that the group targeted acetone because

it is the most volatile byproduct of body fat burning, or

lipolysis. During body lipolysis, byproducts like acetone

move into the bloodstream and eventually find their way

to the pulmonary alveoli in the lungs, where they can be

released from the body via exhalation.

Detecting acetone in exhaled breaths is not very simple,

however. “It is rather challenging to accurately detect

acetone in breath as it occurs at trace level concentrations—

typically parts per million—among more than 800 chemical

species,” Güntner said. To solve this, the researchers decided

to coat the sensor with a highly porous film of tungsten

trioxide doped with silicon atoms. The highly porous nature

of this film allows for easy diffusion of gas molecules and

offers a large surface area for sensing acetone at various

concentrations. The researchers used silicon to stabilize the

tungsten trioxide because the resulting chemical compound

is highly sensitive, selective and stable, allowing for the

sensor to detect acetone exclusively.

To test the sensor, the team collaborated with pulmonary

specialists including the Director of the Department of

Pulmonology, Malcolm Kohler, at the University Hospital

Zurich. Twenty volunteers completed three thirty-minute

sessions of moderate cycling on an ergometer to stimulate

lipolysis, followed by a resting period. During and after the

periods of exercise, the researchers measured breath acetone

profiles by asking the volunteers to blow into a tube that was

fixed to the acetone sensor.

“We observed large variations from person to person,”

Güntner said. “While some volunteers showed increasing

breath acetone concentrations—indicating enhanced body

fat burn—already after a short work-out, it took some others

almost ninety minutes of training.” These results were confirmed

by mass spectrometry and not only indicated that the sensor

could successfully detect acetone as a marker of lipolysis,

but interestingly also provided insight into each volunteer’s

individual metabolic state. Parallel blood measurements of

the biomarker beta-hydroxybutyrate—a standard method

for monitoring body fat metabolism—agreed with the data

collected by the acetone breath sensor, ensuring that the acetone

sensor measurements were indeed accurate.

Alongside these results, the small size and low cost of this

acetone breath sensor prove it to be advantageous over other

similar instruments. According to Güntner, the chip is the

size of a one-cent euro coin (comparable in size to a US

dime) and is fabricated from low-cost components, making

it ideal for integration into a device that can be used at home

or at the gym. Current systems used to measure breath

acetone include indirect calorimetry and mass spectrometric

techniques—methods which are complex, lack portability

and cost thousands of dollars. Portable breath acetone tests

are already available for use, but existing models are either

inaccurate, not reusable, or incapable of detecting acetone

in real-time.

While the researchers refine their prototype breath

acetone sensor, health and fitness fans can look forward to a

new method of personalizing and optimizing their training

routines. The researchers are optimistic about the future

of their one-size-fits-all sensor. “I believe this device could

be quite attractive for athletes to optimize their training

regimens and personal fueling tactics,” Güntner said. “But

also for those who would like to guide dieting toward

effective fat loss.”


December 2017

Yale Scientific Magazine






Growing up five blocks away from the Museum of Natural History

in New York, current senior Alexander Epstein (SY ’18) was constantly

roaming around its exhibitions from a young age. As a child,

he never stopped absorbing new information. Many of the museum’s

teachings surprised him, jump-starting his interest in science;

in particular, he was fascinated with the Vertebrae Evolution Hall

at the museum. “It can prompt you to rethink your entire view of

life,” Epstein said. For example, he discovered there that fish are not

a valid evolutionary group: salmon are more closely related to humans

than to sharks, so there can’t be an evolutionary group that

includes salmon and sharks, but not humans. “As a kid, this made

me rethink a lot of how I felt about the world. It got me into science

again and again,” Epstein said.

During high school, Epstein developed interests in other subjects

as well; he especially enjoyed his history and English classes. He

was on the robotics team and helped build a 120-pound metal robot

to compete in various events. At Yale, Epstein chose to hone in

on his passions by double-majoring in Chemistry and Molecular,

Cellular, and Developmental Biology (MCDB). He feels that Yale is

a great place to study science because it cultivates a nurturing environment,

especially in the upper-level courses. Aside from schoolwork,

Epstein is a Cell Biology peer tutor and was the former Elementary

Curriculum Coordinator for the MathCounts Outreach

program, which aimed to make math accessible to students in New


►Epstein posing next to two giant plush microbes in his lab around

Christmas-time last year.

Haven public schools. Moreover, Epstein is incredibly passionate

about his academic interests, having dedicated his past three summers

to cell biology research.

Epstein began conducting scientific research in high school,

where he worked at a private company near New York City. “In

spite of every failure I had—because research is ninety-nine percent

failure—I still enjoyed it,” Epstein said. As a result, Epstein

was compelled to continue pursuing research at Yale, where he ultimately

ended up working in the lab of MCDB Professor Thomas


Epstein’s research in Professor Pollard’s lab focuses on the actin

filament cytoskeleton, which holds the shape of the cell together.

Actin filaments are composed of protein building blocks that assemble

together into long rods. Like Lego bricks, they can be assembled

into a wide variety of different structures, each of which

serves a special function inside the cell. Epstein is currently studying

the Arp2/3 complex, a protein-based machine that builds huge

branched networks of actin, pushing the front of a cell forward as

it moves and helping the cell to take in nutrients through a process

called endocytosis. He is exploring how the protein complex is regulated,

so that these branched networks are assembled at the right

time and in the right place, supporting successful endocytosis.

Deservedly, Epstein has received recognition for his hard work.

He was awarded the Beckman Scholarship as a sophomore in recognition

of his research background and scientific promise. Each

Beckman Scholar is given financial support to continue their research

over the course of one academic year and two summers.

Epstein was also awarded the Goldwater Scholarship in his junior

year, which recognizes his commitment to research and potential

for being a future leader in his field. The scholarship is one of the

oldest and most prestigious undergraduate awards for students in

STEM fields and provides a substantial scholarship.

Despite his numerous accolades, Epstein is most proud of the

knowledge that he has attained at Yale. “I went in knowing a little

bit of biology and not very much of math and physics—I didn’t

know multivariable calculus—and now I’m taking abstract algebra,

physical chemistry, and have some understanding of quantum mechanics.

What I could do then versus what I can do now… This difference

is what I’m most proud of,” Epstein said.

Next year, Epstein plans on finding a fellowship that will enable

him to do research at Cambridge. He is interested in studying the

structure of protein aggregates, or misfolded proteins clumped together,

which contribute to Alzheimer’s Disease. This type of research

would involve many techniques that Epstein has never performed

before, which he views as a great learning opportunity.

Much like the cells that he has studied at Yale, Epstein is always

moving forward.

36 Yale Scientific Magazine December 2017 www.yalescientific.org


ESTHER CHOO (JE ’94, MD ’01)



When Esther Choo posted a chain of tweets about her interactions

with racist patients in the emergency room, she never expected it to receive

tens of thousands of retweets and over a hundred thousand favorites.

One responding tweet reads, “We’ve got a lot of white nationalists in

Oregon. So a few times a year, a patient in the ER refuses treatment from

me because of my race.” Another says, “Sometimes I just look at them,

my kin in 99.9% of our genetic code, and fail to believe they don’t see

our shared humanity.” The enormous response to Choo’s tweets is bittersweet;

while her words clearly resonated with many, they also demonstrated

how deeply discrimination continues to plague society.

Choo has been using Twitter for almost a decade. Besides her personal

account, Choo also promotes @FemInEM, an organization dedicated to

women in emergency medicine, and @WomenDocs4Hmnty, a group of

women physicians serving those affected by humanitarian crises. “Over

time, I’ve actually started to view it as part of my personal and professional

obligation,” Choo said. “Going on Twitter and talking about some

of these really tough topics is part of my identity now.”

Beyond Twitter, Choo works with organizations like FemInEM and

Physician Mothers Group (PMG). She is a senior advisor to FemInEM,

which addresses the issues holding women back in medicine and what

can be done to overcome these gender disparities. PMG, a group of

70,000 physician mothers across country, has a research arm that studies

how to best support women throughout their careers. Choo also recently

co-founded a company called Equity Quotient, which measures and

addresses the culture of gender equity within healthcare organizations.

Before obtaining her medical degree from the Yale School of Medicine

in 2001, Choo graduated from Yale College in 1994 with a degree

in English. She returned to school and earned a Master’s in Public

Health in 2009 from Oregon Health and Science University (OHSU),

where she is now an associate professor.

Choo believes getting an MPH was the best decision she ever made.

She recognized her interest in health disparities after working in several

safety-net hospitals, which provide care for economically disadvantaged

populations. Her research background now helps her address

how to take care of society’s most vulnerable patients. “I understand

data much better,” Choo said, “When I’m talking about a problem, I’m

able to communicate it better. Then when I work a shift and I’m curious

about things like ‘why do we do that?’, as a researcher, I can turn

that into a research project.”

According to Choo, the biggest obstacle in fighting discrimination in

medicine is that society does not yet fully understand the problem itself.

“I honestly think we’re a bit stuck on characterizing the problem,” she

says. “If you look at the medical literature, there has been a surge of data


►Esther Choo (JE ‘94, MD ‘01) uses her expertise in public health and

her social media presence to fight the discrimination she witnesses

in healthcare.

coming out about the existence of the inequities experienced by physicians

based on race, ethnicity, gender, and more, but there’s still incomplete

data about the nature of problem. We all thought we could jump in

and fix the problem, but to have solutions we need to understand it first.”

Choo’s advice is twofold: first, not to be blind-sided by discrimination

and second, to foster conversation by calling it out when it happens.

“As we move up to positions of influence, we need to realize it’s

our responsibility to change the landscape of medicine for the next generation,”

she said. Joe Robertson, the president of OHSU, demonstrated

this last December when he released a statement saying that hate-speech

and requests for specific physicians based solely on ethnicity would not

be tolerated. Choo thinks the importance of this statement was not an

immediate change of behavior but the solidification of OHSU’s culture.

Many institutions lack such an explicit statement.

Being an activist can be frustrating, but Choo has identified the

things that inspire her to persevere, such as her children and her

Christian faith. She also draws inspiration from the responsibility she

carries as an alumna of an elite institution. “The minute you walk into

Yale, you’re given a position of incredible privilege that almost nobody

else gets,” she says. “My friends were the type of people who recognized

this privilege and didn’t take it for granted. Every minute since

has been about how we pay back.”


December 2017

Yale Scientific Magazine



science in the spotlight




How does an animal transform from a violent hunter into a loyal

companion in the space of just a few generations? Or, put more simply:

what defines a dog? American evolutionary biologist Lee Dugatkin and

Russian geneticist Lyudmila Trut explain the mystery in their new book,

How to Tame a Fox (and Build a Dog). The authors paint a thrilling

portrait of the longest-running experiment in animal behavior: an

attempt to recreate domestication of silver foxes. The conception and

details of the project are placed in the historical context of the Soviet

Union under Stalin and beyond, making the story a mix of scientific

discovery, folk tale and spy novel.

Dmitri Belyaev, the Russian scientist who devised the experiment,

selected silver foxes from commercial fur farms scattered throughout

Russia and gradually turned them into pets. Belyaev’s method was easy:

select the tamest fox pups, breed them, and repeat. The domestication

of wolves was estimated to have taken 15,000 years, but Belyaev’s team

observed changes within only a few generations. To date, they have

bred 56 generations and counting. The first foxes snarled and lunged at

the researchers, who approached wearing thick gloves. Now, the foxes

race towards people, lobbying for pats and nuzzling their caretakers.

Interestingly, these tamer foxes physically resemble dogs more than

their wild predecessors. Their ears are floppy, their fur is piebald, and

their tails wag wildly. New work aims to understand the genetic changes

behind this transformation.

The research setting itself is dramatic, located in freezing Siberia.


Dugatkin and Trut inspire a continual

sense of awe, relaying multiple anecdotes

of the workers’ strength and devotion.

One research project required midnight

blood samples from the foxes. Shifts

lasted three weeks, with temperatures

below -40°F, yet none of the workers

complained, despite having multiple

children at home to care for. Trut

remembers their attitude as “if it was for

science, let’s do it.” Yet, perhaps the most

surprising of the novel’s traits was its

successful evocation of “fear of missing

out,” otherwise known as “FOMO,” in the

reader. Not only was the story gripping and the book hard to put down,

but one feels nearly ready to head to Siberia and meet the foxes—despite

the freezing cold weather!

Tightly-woven, accessible, and engaging, How to Tame a Fox has

received praise from across the board. By incorporating the social

and historical context of the experiment, the authors make the book a

compelling read. Ultimately, the book investigates the interplay of genes,

evolution, and environment on behavior: a new take on the age-old

debate of nature versus nurture. This fantastic and entertaining story is a

relevant reminder of the wonders research can uncover.



Intelligence is simply the ability to solve complex tasks—or so says

Max Tegmark, founder of the Future of Life Institute and author of the

new book Life 3.0: Being Human in an Age of Artificial Intelligence. By

his definition, what separates our problem-solving and thinking abilities

from those of a supercomputer or a calculator? Are we already inferior to

chess-playing computers and statistical models? And most importantly,

what makes us human, if not our superior intelligence? Tegmark poses

and addresses these questions as he seeks to answer both what it means to

maintain our humanity as we develop AI technology and why this issue

is important.

According to Tegmark, Life 1.0 was primarily comprised of bacteria

working towards replication and survival, and Life 2.0 consisted of animals

pursuing goals beyond survival by manipulating their environment. The

first two versions were limited by living creatures’ inability to modify

themselves, but Life 3.0 does not have the same constraint, Tegmark

writes—calling it the “master of its own destiny.” The implications of

computers with an awareness of their own abilities and the cognition

for self-improvement are massive. For one, as he describes, intelligence

is power, and it could be dangerous to give machines with no inherent

ethical mind a position of power. Even though these machines would

theoretically be under human control, artificial intelligence involves

determining the subtasks relevant to successfully completing a larger task,

and with no way to predict these subtasks, it may be impossible to program

a moral, legal and practical mindset into

these machines.

However, Tegmark remains

overwhelmingly optimistic, explaining

that technology is responsible for nearly all

the improvement in quality of life since the

stone age and it will undoubtedly continue

to be moving forward. In bite-sized

chunks of easily-digestible computing

and philosophical concepts, Tegmark

convincingly illustrates the necessity

for further evaluation of our goals as

a society and further planning for AI’s

incorporation into our world—a discussion that Tegmark says may be the

most important conversation of our time.

As either an introduction into the complexity of artificial intelligence

or a further exploration of its potential and moral implicativons, Life 3.0

serves as a magnificent guide with a series of examples and shameless

illustrations. Despite these easily-manageable explanations, Tegmark

never shies away from an issue due to its complexity. Regardless of one’s

field of study or profession, the reader is forced to consider how AI may

impact one’s life and what preparation is required. It may be wise, or

possibly even intelligent, to pick up a copy on the way home today.

38 Yale Scientific Magazine December 2017 www.yalescientific.org

Research: Expectations vs. Reality





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