Joint Colloquium Distinguished Lecture Series
Changing Classes and Inventing Elements: Developing a combined systems biology and engineering approach to designing complex function in cells
Wednesday, April 18, 2012
To meet the goal of creating reliable, predictable, efficient, and transparent methods to harness cellular capabilities for human benefit, it is necessary both to have standard libraries of elements from which useful pathways can be constructed and an understanding of the how host physiology and the environment impacts the functioning of these heterologous circuits. We show how variations in cellular and environmental context affect the operation of the basic central dogma functions underlying gene expression. Then we describe progress on creating a complete, scalable, and relatively homogeneous and designable sets of part families that can control central dogma function predictably in the face of varying configurations, genetic contexts, and environments.
Adam Arkin is PI and Co-Director, Virtual Institute of Microbial Stress and Survival, Co-Director, BIOFAB: International Open Facility Advancing Biotechnology, Director of Bioinformatics, The Joint Bioenergy Institute, Investigator, Energy Biosciences Institute, and Head of the , Synthetic Biology, Physical Biosciences Division, Lawrence Berkeley National Laboratory.
The Arkin Lab works on detailed modeling of genetic and biochemical networks with emphasis on developmental systems. The laboratory creates custom genetic circuitry in Saccaromyces cerivisiae and multichannel, protein and small molecule biosensors. The Arkin Lab is interested in the detailed physical analysis of the network of biochemical and genetic reactions that govern cellular development. The goal is to divine the engineering principles of the control systems that determine cell behavior and differentiation in response to internal and external signals. Because of their simplicity (relative to eukaryotic cells), and because many bacterial genome sequencing projects have recently completed, we study mostly bacterial and viral circuitry. Particular biological systems currently under study in my lab include, l-phage/Escherichia coli interactions, the role of stochastic phase-variation of type-1 pili in uropathic E. coli virulence, and analysis of the sporulation initiation and germination pathways in Bacillus subtilis. As the basis for such analyses we examine the detailed mechanisms of the underlying chemical reactions. For example, a rigorous physical analysis of the mechanisms of prokaryotic gene expression revealed that the temporal pattern of protein production from a single gene is an erratic and bursty stochastic process. Analysis of networks of such genes responsible for developmental switches demonstrated that while some architectures generate deterministic outcomes despite this noise, others exploit the noise to produce population diversity to, for example, evade attack by the immune system. In addition to theoretical analyses, the laboratory has started experimental measurements on such systems and has begun design and implementation (in yeast and E. coli) of our own custom genetic circuitry. Thus, the laboratory applies theoretical and computational analyses from dynamical systems, stochastic processes, chemical kinetics and statistical mechanics and methods from molecular biology to determine the principles of cellular signal processing and to aid in design of custom cellular circuitry that may, for example, act as sensitive biosensors.
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