March 5:

Dr. Eric Eisenstadt

DARPA

How and Why DARPA does Biology

DARPA has recently begun an interdisciplinary research program in neuroprocessing and cellular regulatory networks.  The program integrates state-of-the-art capabilities from the physical, information and
biologicalsciences for the purpose of  a) reaching new plateaus of understanding about the fundamental mechanisms governing the behavior of complex biological systems; b) exploring the potential of biological systems to contribute new ideas/approaches to manufacturing and information technology; c) training a new generation of scientists with fluency in the language and practice of science in all three disciplinary areas; and, d) developing biologically-based technologies that provide DOD with revolutionary capabilities.  Specific examples from DARPA-supported interdisciplinary research activities in cell and neurobiology will be presented in addition to descriptions of other DARPA investments involving the biological sciences.

References:

Elowitz and Leibler

Gardner Collins

Jeong et al. 2000

Brent


Curr Biol 2000 Apr 20;10(8):R318-20

Towards a circuit engineering discipline.

HH McAdams, A Arkin

Department of Developmental Biology, School of Medicine, Stanford
University, Stanford 94305, USA. mcadams@cmgm.stanford.edu

[Medline]

Genetic circuits can now be engineered that perform moderately complicated
switching functions or exhibit predictable dynamical behavior. These
'forward engineering' techniques may have to be combined with directed
evolution techniques to produce robustness comparable with naturally
occurring circuits.


Annu Rev Biophys Biomol Struct 1998;27:199-224

Simulation of prokaryotic genetic circuits.

HH McAdams, A Arkin

Department of Developmental Biology, Beckman Center, Stanford University
School of Medicine, California 94305, USA.

[Medline]

Biochemical and genetic approaches have identified the molecular mechanisms
of many genetic reactions, particularly in bacteria. Now a comparably
detailed understanding is needed of how groupings of genes and related
protein reactions interact to orchestrate cellular functions over the cell
cycle, to implement preprogrammed cellular development, or to dynamically
change a cell's processes and structures in response to environmental
signals. Simulations using realistic, molecular-level models of genetic
mechanisms and of signal transduction networks are needed to analyze dynamic
behavior of multigene systems, to predict behavior of mutant circuits, and
to identify the design principles applicable to design of genetic regulatory
circuits. When the underlying design rules for regulatory circuits are
understood, it will be far easier to recognize common circuit motifs, to
identify functions of individual proteins in regulation, and to redesign
circuits for altered functions.


I won't of course attempt to cover these articles in any detail but they
collectively provide one with a modern view of where I think mechanism-based
simulation of biochemical reaction networks is headed.  The Endy and Brent
review provides a succinct view of the challenges associated with modeling
and simulating cellular regulatory networks.  Jeong et al. is fascinating
but I can't yet tell if there is less there than meets the eye.