Show Changes in Scientific Thinking
The first annual NIH Director's Pioneer Award Symposium in Masur
Auditorium on Sept. 29 featured talks by all nine of last year's
recipients. A key component of the NIH Roadmap for Medical Research,
the Pioneer Awards go to individual scientists with innovative
ideas rather than to particular research projects. As NIH director
Dr. Elias Zerhouni explained in his introductory remarks, the peer
review process tends to keep one eye toward managing risk, thus
favoring more conservative proposals. The Pioneer Awards are a "pilot
experiment," as he put it, to try to unleash more creative potential.
After only the first year of their 5-year awards, last year's
recipients took diverse approaches to their presentations, with
some emphasizing the conceptual problems they were addressing and
others offering several slides of data. One thing was consistent,
however: a picture of researchers ambitiously pursuing innovative
approaches to major biological questions. As Zerhouni observed, "There
was no shortage of bold ideas." Here's a brief survey of the presentations:
- Larry Abbott, a mathematical physicist at Columbia University,
began the talks by speaking about the mathematical modeling of
neural systems. He sees a great divide within neuroscience between
the sensory and the motor systems. What lies between them is
thinking: choices and decision-making. Abbott explained his ambition
to build a mathematical network with some of the properties of
the brain. Mathematicians can now build quite good networks of
complex activity, he said, but sensitivity to the outside world
is still lacking. His goal is to get these networks to pay attention
to the outside world and to be able to formulate a response.
- George Daley of the Harvard Stem Cell Institute explained how
he aims to discover the principles underlying the epigenetic
code — that is, what determines how genetic information
is used. Stem cells promise to reveal the interplay of genes
during development in ways scientists haven't yet been able to
address. Daley's strategy is to alter cell culture conditions
to reproduce critical cell fate transitions in vitro.
His lab has already been able to reproduce several of these transitions.
|At a Sept. 29 press briefing to discuss
progress in the NIH Roadmap for Medical Research and introduce
the 2005 NIIH Director's Pioneer Award recipients, awardee
Derek Smith of the University of Cambridge (at head of table)
discusses how his mathematical approach to understanding and
controlling the evolution of pathogens could be applied to
prevent a flu outbreak.
- Homme Hellinga of Duke University Medical Center is designing
proteins with desired functions, a process he calls synthetic
biology. He showed how a receptor can be used as a biosensor
for a variety of compounds by redesigning its binding site. The
process, which involves complex computational design in 3-D space,
can already reengineer proteins to bind metabolites, drugs, explosives
and pollutants. Eventually, Hellinga hopes to be able to design
complete biological pathways, such as signal transduction circuits
that can survey the cell's chemical environment and respond to
- Mike McCune of the University of California at San Francisco
explained how Macaque monkeys infected with SIV, the simian equivalent
of HIV, develop a rampant inflammatory response after infection
and subsequently die of immunodeficiency. African green monkeys,
in contrast, have a high viral load but don't develop an inflammatory
response and don't develop immunodeficiency. There is a balance,
Mc-Cune said, between antiviral immunity, which attempts to clear
the virus from the system, and proviral inflammation. While much
of the research community's focus has been on antiviral immunity,
McCune's hope is to improve survival by reducing humans' inflammatory
response to HIV. He pointed out that a better understanding of
the human immune system is emerging from the study of HIV pathogenesis
that will affect our thinking about many other diseases that
cause chronic inflammation.
|NIH director Dr.
Elias Zerhouni responds to a reporter's question at the press
- Steve McKnight of the University of Texas Southwestern Medical
Center is studying yeast as they cycle between oxidative and
glycolytic metabolism. McKnight's hypothesis is that circadian
rhythms evolved from a "metabolic cycle" like that seen in cultures
of baker's yeast, and he hopes his studies will shed light on
circadian rhythm. Using a microarray analysis of gene expression
during metabolic cycling of a dense yeast culture, his lab has
already identified many periodic genes that "cycle spectacularly."
- Chad Mirkin of Northwestern University described several projects
in his attempt to build a suite of nanoengineering tools. One
is "dip-pen nanolithography." Adapted from atomic- force microscopy,
the technique uses an array of "pens" to deliver reagents to
a surface in particular patterns. Chemical manipulations at the
tips can also control molecular orientations. Nanoarrays built
with different patterns and combinations of molecules can help
researchers explore cooperation and interaction between molecular
structures. Mirkin's lab has already built nanoarrays of virus
particles to explore how their structures interact with cell
surfaces in culture.
|At the first annual
NIH Director's Pioneer Award Symposium in Masur Auditorium,
the 2004 Pioneer Award recipients participate in a panel discussion
on innovative research.
- Rob Phillips of the California Institute of Technology hopes
to use mathematics and physics to transform an empirical understanding
of biological events into a quantitative understanding — in
other words, to recast biological models in mathematical terms.
As an example, he explained how the forces resulting from the
looping and bending of DNA molecules have biological consequences.
His lab is trying to predict gene expression in the lac operon
by computing the statistical weights of different states of its
DNA loop. They are also studying the mechanical forces involved
in packing long chains of DNA into virus capsids. By varying
osmotic pressure and DNA length and then measuring how the DNA
ejection rate changes, they hope to gain a quantitative understanding
of how these viruses inject their DNA into bacteria. Phillips
is applying his new thinking about the interface between physics
and biology to write a textbook about the physical biology of
- Stephen Quake of Stanford University is developing a technology
called microfluidics. He designs microchips that use tiny volumes
of fluid and contain a maze of channels, valves and collection
wells. He can design these chips for ultra sensitive gene expression
analysis, for cell culture experiments with single cells and
to grow protein crystals for protein structure studies. These
small volumes not only consume tiny amounts of precious supplies,
but also the fluid physics in such small volumes actually favor
certain types of experiments, like protein crystal formation.
- Sunney Xie of Harvard University aims to develop the technology
to view single molecules inside live cells. The research community
has until recently been looking exclusively at data capturing
large numbers of molecules at once. To understand how molecular
machines actually work, however, we need to see single molecules
working in real time inside live cells. Xie's group has recently
been able to observe the production and degradation of single
proteins in live E. coli cells for the first time. They
hope to advance and apply the techniques they have developed
to examine many fundamental processes in biology.
This year's 13 Pioneer Award recipients, who were named at the
symposium, are pursuing a similarly expansive range of projects,
from Giulio Tononi's exploration of why we sleep to Nathan Wolfe's
collaboration with subsistence hunters in regions of high biodiversity
to monitor the entry of novel viruses into the human species.
In introducing the new recipients, Zerhouni said, "The Pioneer
Award to me is like the scientific freedom award. We want to give
them the freedom to explore."
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