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10<br />

SCIENCE<br />

And a few suggestions...<br />

Uncle Tungsten<br />

by Oliver Sacks<br />

In this charming biography, Sacks gives a wonderfully<br />

vivid account of his earlier years and his fascination<br />

with chemistry. Evoking memories of his<br />

family and their fascination with science, he paints<br />

a picture of the environment that fostered his curiosity<br />

and inquisitiveness. Sacks proves himself to be a<br />

brilliant storyteller; his accounts of boarding school<br />

and the return to home life where he nurtured his<br />

passion for science are witty and endearing.<br />

Particularly poignant are his dry humour and careful<br />

comedy, a welcome addition to what is a highly<br />

emotive biography (apparently moving some readers<br />

to tears). What is most inspiring is the innocence of<br />

Sack’s early fascination with chemistry; he is now<br />

a highly distinguished neurologist and a respected<br />

figure in popular science. This innocence leaves us<br />

with a sense of resolve; after all, this brilliant mind<br />

was once a child too. Katya-yani Vyas<br />

Schrödinger’s lolcat<br />

Fantastic phenomenon from the<br />

Natural World<br />

A boa constrictor has given birth without mating. ZZ<br />

chromosomes produce males and ZW produce females,<br />

but these baby snakes have WW. She gave<br />

birth through parthenogenesis (half-cloning) when<br />

there were four courting males in her enclosure.<br />

FELIX<br />

Science Editors: James Goldsack<br />

Katya-yani Vyas<br />

science.felix@imperial.ac.uk<br />

The retrovirus conundrum<br />

How do retroviruses insert their genome into host DNA?<br />

Victoria Bignet<br />

Imperial College researchers from the Department<br />

of Infectious Diseases have just succeeded<br />

in determining the mechanism of retroviral<br />

integration, using x-rays to analyse the key molecular<br />

structures involved in this process.<br />

The Diamond synchrotron in Oxfordshire<br />

was the researchers’ main tool to produce intense<br />

X-ray beams enabling them to observe<br />

molecular interactions. “This kind of fundamental<br />

research is vital if we are to advance<br />

our understanding of the viruses and diseases<br />

that affect millions of people around the world.<br />

Knowing the 3D structure of the mechanisms<br />

involved is like being able to see inside the engine<br />

of your car. If you can actually see what<br />

is happening, you get an idea of how you can<br />

fi x it”, says Professor Thomas Sorensen, who<br />

is Principal Beamline Scientist at the Diamond<br />

synchrotron.<br />

A retrovirus relies on its host-cell machinery<br />

to replicate its genome. The latter is in the<br />

form of RNA, and is converted to DNA once in<br />

the host cell. Viral DNA must then be inserted<br />

within host-cell chromosomal DNA. The way<br />

this insertion is carried out has, up till now,<br />

been a biological enigma. The Imperial College<br />

researchers have managed to describe a<br />

key agent in this vital step for the virus: the<br />

intasome, a nucleoprotein complex composed<br />

of an integrase tetramer (IT). Integrase is a formerly<br />

known enzyme which confi nes and fuses<br />

the ends of viral and host DNA together.<br />

Prototype foamy virus (PFV) is very similar<br />

to HIV in its way of integrating its genome.<br />

With the synchrotron, the authors analysed<br />

crystal structures of host DNA in complex with<br />

the intasome of PFV. That is, the 3D structures<br />

of integrase bound to both viral and host DNA<br />

in atomic detail. From this observation, the authors<br />

elucidated the confi nement mechanism<br />

of target DNA before integration, as well as<br />

the intermediary steps of post-catalytic strand<br />

transfer. “Only 18 months ago we had a rather<br />

sketchy understanding of retroviral integration”,<br />

says Dr Peter Cherepanov from the Department<br />

of Medicine.<br />

Two integrase tetramers (ITs) come together<br />

to form a narrow cleft, which accommodates<br />

the host DNA in a highly bent confi guration,<br />

facilitating access for IT active sites to the scissile<br />

phosphodiester bonds. For insertion into<br />

chromatin, the ITs are thought to interact with<br />

host nucleosomal DNA , and/or the histone octamer.<br />

Once this is performed, the phosphodiester<br />

linking viral and host DNA gets ejected<br />

out of the active site. As expected from knowl-<br />

edge on the relatively low degree of sequence<br />

selectivity of retroviruses for chromosomal<br />

DNA, interactions between IT and host DNA<br />

bases are sparse. Indeed, strong selectivity for<br />

chromosomal DNA would limit possible integration<br />

sites and thus reduce viral fi tness. Yet<br />

two sites of close contact were identifi ed.<br />

In the context of gene-therapy, Cherepanov<br />

stresses that: “one of the main problems with<br />

the current method is that retroviral integration<br />

is too random. [...] Ideally, we want to insert<br />

therapeutic genes in predefi ned, safe locations<br />

of the human genome”. With these fi ndings,<br />

one could theoretically create site-specifi c<br />

retroviral vector systems by designing an integrase<br />

with higher selectivity for a wanted target<br />

DNA sequence.<br />

The synthetic retrovirus could insert a functional<br />

copy of a desired gene into a human chromosome<br />

by greater certainty of insertion site.<br />

This greatly improves the technique’s safety by<br />

for instance reducing the risk of activating an<br />

oncogene, thereby avoiding the reoccurrence<br />

of former cases such as leukaemia in treated<br />

patients. The discoveries would also help improving<br />

existing antiviral strategies, facilitate<br />

the design of better drugs to combat AIDS, and<br />

stimulate novel approaches to blocking viral<br />

replication.<br />

Huge leap in quantum computing<br />

Kelly Oakes<br />

Do you think you could make sense of this<br />

sentence if every fourth word was missing?<br />

How about trying to hold a conversation when<br />

you can only hear three quarters of what the<br />

other person is saying? Cutting out a fraction<br />

of the information being transferred in a given<br />

situation may make life slightly diffi cult, but it<br />

certainly doesn’t stop the meaning being conveyed<br />

in most cases. This is because of the redundancy<br />

built into language. However, redundancy<br />

is not only useful for conversations on a<br />

dodgy phone line - it can also come in handy<br />

in the world of quantum computing, as two<br />

researchers explained in a paper published in<br />

Physical Review Letters last week.<br />

The research was carried out by Sean Barrett,<br />

of Imperial College, and Thomas Stace, at the<br />

University of Queensland in Brisbane, Australia.<br />

They found that if a quarter of the qubits<br />

(the quantum equivalent of bits, which store information<br />

in a classical computer) are lost, the<br />

computer can still function as normal. Barrett<br />

and Stace looked at the remaining information<br />

and used a code that could check for errors to<br />

decipher what was missing. “It’s surprising,<br />

because you wouldn’t expect that if you lost<br />

a quarter of the beads from an abacus that it<br />

would still be useful,” said Dr Barrett.<br />

One of the main differences between a classical<br />

bit and its quantum equivalent is that the<br />

latter can exhibit entanglement. This means<br />

that, no matter how far away two entangled<br />

qubits are, if one changes so will the other - instantaneously.<br />

Quantum computers take advantage<br />

of this effect, as well as another property<br />

of quantum systems known as superposition,<br />

to perform complicated calculations much<br />

faster than classical computers. At the moment,<br />

though, the largest quantum computers have<br />

only two or three qubits.<br />

It had previously been thought that large<br />

quantum computers would be very sensitive to<br />

missing information, but this research shows<br />

that they should be much more robust than<br />

we’d imagined. At this stage, the work is theoretical<br />

and scientists must do a lot more in order<br />

Friday 19 November 2010<br />

See? The future isn’t ‘orange’ at all! Idiots... It’s quite obviously blue and whooshy<br />

to make quantum computers bigger than a few<br />

qubits in the lab.<br />

When large quantum computers are a reality,<br />

they may have the potential to revolutionise<br />

fi elds as far apart as drug modelling, electronics<br />

and code breaking. However, we won’t<br />

know exactly what applications quantum computers<br />

will be best suited to until we’re able to<br />

make one.<br />

“At the moment quantum computers are good<br />

at particular tasks, but we have no idea what<br />

these systems could be used for in the future,”<br />

said Dr Barrett. “They may not necessarily be<br />

better for everything, but we just don’t know.<br />

They may be better for very specifi c things that<br />

we fi nd impossible now.”

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