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Research update from the Institute for Molecular Bioscience

No.

14

Winter 08

Medical research to be quicker and cheaper with

new gene sequencer

Fellowship for smart IMB researcher

Industry and researchers join forces to

develop better biofuels

Researchers investigate alternative to

embryonic stem cells

Biochemistr joins IMB from Germany

Fear and bacteria: possible ways of controlling the

cane toad

Scientists identify hidden layer of brain function

In Brief

Next Smart State Strategy stage announced at IMB

Graduates around the globe

Medical research to be quicker and cheaper with new

gene sequencer

An Australian research team has pioneered a new approach to studying gene content and activity that stands to

revolutionise the future of genetics.

Since the completion of the human genome project, one of the “holy grails” for medical researchers has been to

work out how to accurately survey the DNA code and gene activity of more than 25,000 genes in normal cells and to

identify the mutations or alterations driving genetic diseases.

Associate Professor Sean Grimmond from the Institute for Molecular Bioscience led an international team that

has recently shown it is now possible to sequence the DNA code of every gene in a biological sample in a single

experiment.

“This new method, which we call the SQRL method, vastly increases the scope of research which a single laboratory

can undertake, and the pace at which it is completed,” Dr Grimmond (pictured right) said.

“The completion of the Human Genome Project took worldwide effort, an estimated US$2.7 billion dollars and 13

years to complete. In testing this new approach, we were able to sequence four times the sequence content of the

entire human genome in our laboratory at only a fraction of the cost.”

Dr Grimmond and his team had focused on sequencing

RNA in normal cells grown in the lab but they have

recently moved onto studying cancer. It has long been

known that cancer develops as a consequence of the

accumulation of genetic damage, however identifying

these events has previous been a slow and painstaking

process.

Genome sequencing of the entire genetic code of

tumours stands to revolutionise our understanding of the

underlying mechanisms that initiate cancer growth and promote cancer development.

“It’s only going to get faster from here. For example, we have completed a survey of the cancer transcriptome,

which only took a month, and we are compiling the results of that survey now,” Dr Grimmond said.

“What this technology will mean for the future is smaller numbers of scientists can make bigger discoveries, and

we should see outcomes being generated more quickly.”

The research was done using the SOLiD TM Sequencing System from Applied Biosystems, whose researchers

helped to develop the sequencing method. SOLiD TM is a next-generation sequencer that can generate up to 8

billion base pairs of sequence data per run (the human genome has 3 billion base pairs).

Dr Grimmond’s laboratory was one of the first in the world to receive the SOLiD TM sequencing equipment as part

of an early-access program to develop applications for this technology in conjunction with Applied Biosystems.

Details of the SQRL sequencing method and its application to sequencing RNA have been published in the highimpact

international journal Nature Methods.

(Left) Dr Brooke Gardiner, who runs the machine, with the SOLiD TM sequencing system.

www.imb.uq.edu.au


Fellowship for

smart IMB

researcher

IMB researchers will be developing new

anti-cancer drugs thanks to funding from the

Queensland State Government.

Dr Norelle Daly was recently awarded a

$300,000 Smart State Fellowship to develop a

new generation of cancer therapeutics.

The fellowships provide funding for early or

mid-career researchers to undertake innovative

research in Queensland.

Dr Daly and her team will investigate using

peptides, the building blocks of proteins, to form

the basis of a new type of stable therapeutics.

“Until recently the use of peptides as

therapeutic drugs has been considered nonviable

because of problems with their stability

and delivery within the body,” Dr Daly said.

“My project will focus on fusing peptides to a

circular protein framework that will overcome

these problems, and result in a drug with far

fewer side effects than existing anti-cancer

drugs.”

The worldwide market for peptides in 2007 was

estimated at more than $3 billion.

Dr Daly will study two families of circular

peptides, both of which are derived from plants.

One family has been shown to selectively

kill cancer cells, while the other can inhibit

the activity of an enzyme involved in the

progression of cancer.

“Using this two-pronged approach increases

the chance of success in developing a peptide

with better anti-cancer properties that can

then be further developed into therapeutics for

cancer treatment,” Dr Daly said.

She and her team are conducting the work in

conjunction with Professor Marilyn Anderson

from La Trobe University in Melbourne.

The research is being co-sponsored by the

IMB and Hexima.

Industry and researchers join forces to

develop better biofuels

Researchers from the University of

Queensland and Germany have teamed

up with international companies to drive

the development of microalgae for the

production of carbon-neutral biofuels

which do not compete with food production

and which can use saline water sources.

Associate Professor Ben Hankamer from

UQ’s Institute for Molecular Bioscience

will lead the collaboration between the

researchers, Pacific Seeds and Advanta

India, which has received $674,344 over

four years from the Australian Research

Council (ARC). Dr Hankamer last year

established the Solar Bio-fuels Consortium

(www.solarbiofuels.org) to bring together

researchers to develop this technology.

Algae naturally capture sunlight and use its

energy to yield feedstocks for the production

Associate Professor Ben Hankamer with the engineered algae.

of biofuel. The group is developing ways of

enhancing the efficiency of producing hydrogen as well as oil for biodiesel synthesis.

“A project of this scope needs industry support in order to bring it closer to commercial reality,” Dr Hankamer said. “Pacific Seeds

and Advanta India will provide considerable monetary and in-kind support for the project, offering access to research capabilities

and facilities, as well as to staff in Australia and India.”

Advanta India will contribute over $450,000 of in-kind support, including the collection of algae from a variety of Indian locations and

its subsequent testing by the researchers in Australia. The global seed company will also help develop fertiliser for the bioreactors

as well as feasibility studies.

Pacific Seeds, a Toowoomba-based company owned by Advanta India, will provide $168,000 in cash and $174,000 in-kind support,

including algal collection and testing capabilities, as well as support for a PhD student to work on the project. As well as Australia

and India, the Advanta group has subsidiary companies in north and south America and Asia and is actively pursuing and

researching alternative feedstocks for bioenergy production.

Following successful outcomes of the project, it could see solar-powered bioreactors placed in arid or drought-stricken parts of

Australia, India and elsewhere that will produce fuel without emitting carbon or using crops that could be grown for food.

The ARC funds were awarded through the ARC Linkage Projects scheme, which funds collaborative projects that encourage and

develop long-term strategic research alliances between universities and other organisations to obtain national economic, social

or cultural benefits.

Schizophrenia researchers welcome new

blood

An IMB researcher has helped develop a technique to measure levels of vitamin D in small amounts of blood that will be used in a

world-first trial into the link between prenatal vitamin D levels and schizophrenia prevalence.

The trial, funded by the NHMRC and led by Queensland Brain Institute researcher Dr Darryl Eyles, will examine blood spots taken

from newborn babies who have gone on to develop schizophrenia in early adulthood.

“Undeniably, low maternal vitamin D affects the way the brain develops,” Dr Eyles said.

“Over the past four years we’ve been able to show that low vitamin D intake in animals during pregnancy results in offspring with

brain abnormalities similar to those seen in patients with schizophrenia.”

The next step of the research process involves testing the hypothesis on human samples.

By analysing the blood spots of newborns the team will have a good indication of the baby’s vitamin D status at the time of birth.

The blood samples are from the Statens Serum Institute in Copenhagen, but the Danes are only able to give the UQ researchers

1.6 microlitres of plasma per sample.

“We’ve had to come up with a method of determining the vitamin D levels in that tiny amount of blood,” Dr Eyles said. “In

collaboration with Alun Jones at the Institute for Molecular Bioscience, we’ve developed a way to easily measure low levels of

vitamin D using mass spectrometry.”

Mass spectrometry is used to find the structure of a molecule by identifying the abundance and type of atoms that make up the

molecule.

It is expected that the team will begin analyzing 2000 Danish blood spots (1000 cases and 1000 matched controls) in September.

“If we establish the link in this huge patient cohort, we will be able to show that having low maternal vitamin D does not necessarily

mean a child is going to develop schizophrenia but, if a child has a particularly vulnerable genome, the low maternal vitamin D may

be the environmental trigger,” Dr Eyles said.

Dr Norelle Daly uses a nuclear magnetic resonance spectrometer.

“It’s the combination of gene and environment which triggers the disease.”

Schizophrenia affects approximately one percent of the world’s population and is characterised by disruptions in language,

thought, perception, social activity, and volition.


Biochemist joins IMB from Germany

A respected biochemist who has worked for the past decade at the

Max-Planck Institute of Molecular Physiology in Dortmund, Germany,

will join the IMB in September.

Professor Kirill Alexandrov will conduct research and share his

expertise in protein engineering and production.

“Production and engineering of proteins is a key methodology of

life sciences in general and biotechnology in particular,” Professor

Alexandrov (pictured below) said.

“Our ability to produce and analyse the protein-based components of

the cell determines the expense and speed of discovery and creation

of new vaccines, drugs and diagnostic methods.”

Professor Alexandrov has spent most of his research career

developing new research tools and using them to study the protein

machinery that underlies the intracellular transport of vesicles. These

membrane bubbles are responsible for the storage and transport of

substances around the cell, and thus have a role in many cellular

processes and their pathologies.

Professor Alexandrov has made several significant contributions

in the area of biochemistry of posttranslationally modified proteins

and methods of their production and engineering. His team also

pioneered the use of the parasite Leishmania tarentolae in the

production of recombinant proteins. The latter development opens

the way to rapid protein engineering and analysis, leading to better

and cheaper diagnostics and potentially biopharmaceuticals.

Shifting around the globe to continue his research was not a decision that Professor Alexandrov took lightly, however he was

drawn by the people and facilities at the IMB and the neighbouring institutes on campus.

IMB is a rising star of international biomedical research. Multiplied by the Australian commitment to the knowledge-driven

economy and infrastructural integration, it is bound to become one of the most respected international centres,” Professor

Alexandrov said.

“The combination of state-of-the-art facilities and key technologies with the critical mass of researchers in chemical and structural

biology, molecular cell biology and, very importantly, genomics and computational biology provides an ideal environment for

cutting-edge interdisciplinary research.”

Professor Alexandrov grew up in Russia and completed his undergraduate degree at what was then Leningrad State University.

Following a training period in the US he returned to Europe and completed his PhD thesis at the European Molecular Biology

Laboratory in Heidelberg.

“Kirill is a very talented researcher whose expertise will add greatly to the depth at the institute,” IMB Director Brandon

Wainwright said. “I am delighted to welcome him.”

Fear and bacteria: Possible ways of

controlling the cane toad

Scaring cane toads and targeting their bacteria are two control strategies that

were suggested by an IMB scientist at the Australian Vertebrate Pest Conference

in Darwin.

Professor Rob Capon presented the findings of a two-year study that charted the

chemical ecology of the Australian cane toad.

“Our studies have revealed for the first time a range of potential control strategies

that could selectively target and reduce the survival of cane toad eggs, tadpoles and

adults,” Professor Capon said.

Scientists identify

hidden layer in

brain function

Hundreds of new molecules that are likely to

be important for brain function, and ultimately

human development, have been identified by

scientists from the IMB.

The molecules, known as long non-coding

RNAs, are derived from parts of the genome

that do not encode proteins and until now have

been largely regarded as non-functional or

“junk” DNA.

The researchers, including Dr Marcel Dinger

and Mr Tim Mercer and led by Professor

John Mattick, discovered that many of these

molecules are turned on, or expressed, in parts

of the brain responsible for important functions,

including memory formation, behaviour and

sensory perception.

They made the breakthrough by analysing a

newly developed set of maps of the patterns

of RNA expression in the mouse brain. It

follows a number of other recent investigations

that reveal mammal genomes contain much

more information than would be needed to

just encode proteins, which form the major

functional machinery of cells.

“Comparisons between the genome sequences

of diverse animals ranging from worm and fruit

fly to mouse and human showed that the number

of protein-coding genes was largely the same

despite the tremendous differences in their

developmental and neurological complexity,”

Dr Dinger (pictured below) said.

“One possibility to explain this apparent

paradox is that the non-protein-coding regions

of the genome, which become progressively

larger in more complex organisms, provide an

additional layer of information that is required

to regulate developmental processes.

“This new research supports this idea by

showing many of these non-coding regions

are used as templates to produce RNA in very

specific regions and cell types, both in the

developing embryo and in the brain.”

The discovery provides a new understanding

of how the brain works and in the future may

provide additional avenues for the development

of drugs to treat neurological conditions such

as Alzheimer’s Disease and dementia.

The next challenge for the team is identifying

the predicted tens of thousands of noncoding

RNAs that are functional in mammalian

genomes and contain the important information

that underpins our growth and development,

and is responsible for many of the differences

between individuals.

Together with Professor Rick Shine and his team at the University of Sydney, the UQ

researchers led by Professor Capon are close to identifying an alarm chemical in

the cane toad tadpole. When exposed to this chemical, the tadpoles become scared

and flee, only to undergo premature metamorphosis (transformation into a toad),

resulting in underweight toadlets with a lower chance of survival.

“Once this alarm chemical is identified it could be developed into a non-toxic,

biodegradable and species-specific product that could be used in controlled waterways during the breeding season to stress the

toads and lower the numbers that are produced in successive generations,” Professor Capon said.

The study also revealed for the first time the relationships between cane toads and bacteria. Another strategy to be presented

by Professor Capon involves targeting these bacteria, which are capable of transforming and chemically diversifying toad toxins.

Chemically diverse toxins are more effective against a wider cross-section of predators, which enhances toad survival.

“Our studies suggest that bacteria impact cane toad ecology in other ways, by influencing behaviour in egg laying and in protecting

eggs from infectious disease and predation,” Professor Rob Capon.

“The relationship between cane toads and bacteria may be the weak link, and by exploiting this weakness we may be able to halt

the cane toad invasion of northern Australia.”

The study examined all life stages of the cane toad, analysing toxic and hallucinogenic chemicals and alarm pheromones in the

hope of finding a way to minimise the toad’s impact on fragile Australian ecosystems.


In Brief

Next Smart State Strategy stage announced

at IMB

I

PhD student Jane Lattin from the Sweet lab

took out 2nd prize for her oral presentation

at the Australian Society for Medical

Research Queensland Postgraduate Student

Conference.

Mrs Lattin (pictured below) is studying betaarrestins,

proteins involved in the regulation of

the body’s immune response.

Nearly 100 students attended the conference

and presented their research in poster form. Six

were then chosen to give oral presentations.

Mrs Lattin and Uda Ho from the Wainwright lab

were also on the organising committee for the

conference.

The Queensland Premier visited

the IMB in May to announce the

next phase of the Smart State

Strategy and to tour the IMB

labs.

Vice-Chancellor Professor Paul

Greenfield, who was present

at the announcement, said

the next phase’s emphasis on

support for researchers would

help consolidate Queensland’s

burgeoning research community,

which a decade of Smart State

policies has energised and

transformed.

“The first ten years of Queensland

Government Smart State

investments have catalysed

developments in research that

would otherwise have taken decades

to achieve,” Professor Greenfield

said.

IMB Deputy Director (Research) Professor Jenny Stow (left) talks to Premier Anna Bligh

“The concept of ‘critical mass’ in our research community, particularly in areas such as medical science, biotechnology and

nanotechnology has shifted from ideal to reality in the past decade.

“By trebling support for scholarships, fellowships and other grants to individual researchers, the strategy will enhance

Queensland’s attractiveness as a destination for researchers at various stages of their careers.

“UQ has been a partner in Smart State since day one and has consistently matched government funding and secured additional

support from industry, Commonwealth agencies and other organisations.

“The University now looks forward to a continuing role in building Queensland’s international reputation as a place that values

and encourages discovery, particularly in fields that may improve human and environmental health and wellbeing,” Professor

Greenfield said.

Seven IMB students have been named on

the University of Queensland 2007 Dean’s

Commendation List, recognising the outstanding

quality and exceptionally innovative nature of

the research performed for their PhD thesis.

Fewer than 10 percent of PhD graduates are

recognised in this way each year.

The seven successful students were: Marion

Loughnan (Lewis group), Jason Kay (Stow

group), Julita Imperial (Alewood group),

Christian Gruber (Craik group), Melissa Davis

(Teasdale group), David Woolford (Hankamer

group) and Ranjala Ratnayake (Capon group).

IMB Director Professor Brandon Wainwright

said it was testament to the hard work and

dedication of both students and supervisors

that the IMB had received so many citations.

“We are thrilled that nearly a third of our

2007 graduates were recognised in this way,”

Professor Wainwright said. “It is pleasing to

know that even our youngest scientists are

setting the bar high in terms of research.”

IMB student society SIMBA and IMBcom

recently organised the first Great Debate.

With both group leaders and PhD students

participating, the teams debated the topic,

“Bringing the sexy back into science”. The very

entertaining event involved singing, dancing

and tight leopardskin pants and because, or

perhaps in spite, of this, the affirmative team

won. Congratulations to Glenn King, Matt

Sweet and Rehan Villani for their win, and

challengers Jenny Martin, Kate Ewen and Zach

King. Acknowledgement must also go to Peter

Isdale, CEO of IMBcom, for chairing the event,

and Paul Ellender for organising it.

UQ Deputy Vice-Chancellor (Research) Professor David Siddle, said the announcement signalled that the government listened

to advice about the need to back up its foundation investments in infrastructure with support to attract and retain high-quality

people.

“UQ has been a major beneficiary of infrastructure funding, including for buildings, laboratories and items of equipment that are

accessible to researchers from other institutions around Australia and the world,” Professor Siddle said.

“The government has already made significant contributions to researchers, and the new focus shows an appreciation that

excellent researchers are a blue chip investment prospect.”

IMB also hosted the launch of the second stage of Smart State, by former Premier Peter Beattie in April 2005, and was the first

institute to be funded under the Smart State Strategy.

Graduates around the globe

Several IMB students donned their cap and gown to graduate at the University of Queensland’s mid-year graduation ceremony.

Eight students in total had their doctorates awarded, and while some students have stayed at UQ, others have scattered further

afield. Their thesis titles and destinations are listed below:

Cheong Xin Chan Units of Genetic Transfer in Prokaryotes University of Iowa, USA

Jennifer Fleming

Melissa Gardiner

Praveen Madala

Madhavi Maddugoda

Rebecca Pelekanos

Donald Roberts

David Woolford

Biobanks: Professional, Donor and Public

Perceptions of Tissue Banks and the

Ethical and Legal Challenges of Consent,

Linkage and the Disclosure of Research

Results

Determining the role of klf4 in zebrafish

development

The Role of Myosin VI in E-Cadherin

Contact Biogenesis

A Melanocyte-Keratinocyte Coculture

Model to Study MC1R Dependent

Pigmentation Responses

Software Advances and Applications in

Cryo-EM

Princess Alexandra Hospital, Brisbane

Queensland Brain Institute

IMB

Mediterranean Centre of Molecular

Medicine, France

Mater Medical Research Institute

Family Business

Baylor College of Medicine, Texas, USA

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