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The Boss

Biography of Adam Arkin

b. 1966; B.A. Carleton College (1988); Ph. D. M.I.T. (1992) ; Faculty Scientist, Physical Biosciences LBNL (1998-); Assistant Professor, Bioengineering and Chemistry, University of California Berkeley. (1999-); Assistant Investigator, Howard Hughes Institute of Medical Research (2000-)

1999 TR100 Most Innovative Young Scientists Award

 

Research Interests

Physical Chemistry of the Cellular Interior

The interior of both prokaryotic and eukaryotic cells are a very non-classical environment as far as the assumptions of most physical chemistry is concerned. The solutions are not really aqueous; there is a great deal of organization and inhomogeneity in the chemical concentrations; macomolecules are densely packed together, there are mechanical coupling to the chemistry; and many processes are driven by numbers of molecules and at rates slow enough that the thermal fluctuations in reaction rates become significant. We re-examine the thermodynamics, statistical mechanics and kinetics of gene expression, biochemistry and morphogenesis under these novel conditions to try and understand the physics of the cellular environment.

Nonlinear and Stochastic Dynamics

The physical chemical theories give rise to equations that describe biological processes such as gene expression, protein transport and catalysis, and cell membrane potentential. These equations are nonlinear and often contain stochastic components. We are interested in application and extension of bifurcation theory, stochastic process theory and stoichiometric network analysis to the dissection and reduction of these equations to better elucidate the fundamental system dynamics and points of control in cellular networks.

Analysis and Modeling of Cellular Processes

Cellular behavior and develop is governed by a complex network of interacting chemicals that are spatially dispersed throughout the cell. We are developing models of these processes (for particular functions of particular cells) at many different levels of abstraction ranging from detailed physical chemical models to qualitative logical models. We are developing theories for how large networks of chemical reactions can be decomposed into sub-networks that can be analyzed without direct reference to the rest of the cellular environment. We are also developing control theories that predict pathways critical to the qualitative behavior of the network and indicate entry points for the external control of this behavior.

Analysis of Biological Data

In order to deduce and parameterize the network models for the particular organism understudy, typically a large amount of experimental data is necessary. The types of data we have at hand are genomic sequence, gene, protein and metabolite expression data (often from microarrays, 2D protein gel, or capillary electrophoresis measurements), nomarski and fluorescence microscopy images, in vitro enzymological studies, and gross phenotypic data such as growth rates, population heterogeneities, etc. We are developing experimental quality control protocols, statistical data analyses and network deduction algorithms for deriving and validating functional models of signal transduction, developmental and metabolic pathways mostly in prokaryotes. We are also interested in nucleotide and protein sequence and structure analysis in so far as it helps us predict network structure and function and in the design of novel genetic circuitry.

Bioinformatics

Here we define Bioinformatics narrowly to be the theory and application of the storage and retrieval of complex biological data. We are engaged in constructing and curating databases whose information spans the hierarchy of biological phenomena, from genes to tissues, that are necessary for the analysis of regulation. Integrated knowledge and databases of pathway data, kinetic and mechanistic information, molecular profiling and interaction data, and image data linked to external databases of protein and gene sequence, structure and function are under development.

Biosensors

We are starting to develop biosensors to rapidly and sensitively detect metabolites and proteins in a massively parallel fashion analogous to DNA microarrays.

Genetics and Cell Biology

We have two different types of experimental efforts in this regard. The first is in using the theories of genetic and biochemical control we have developed to design and build custom genetic circuitry that behaves in a specified way (toggle switches, pulse generators, etc) in the cell in response to various signals. These are both to serve the role of cell-based biosensors and as a means to probe the cellular environment. The second are experiments driven by the analysis of particular biological systems that answer particuar questions or address missing data needed by that analysis.

 

 

Department of Bioengineering, University of California, Berkeley, CA 94720
Physical Biosciences Division, 1 Cyclotron Road, MS Stanley, Lawrence Berkeley National Laboratory, Berkeley, CA 94720
(tel) 510-495-2116   (fax) 510-486-6219
© Adam Arkin, 2000,. All Rights Reserved

 

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