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Bacteria Meet Physics”

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Bacteria Meet Physics” June 16, 2007 Workshop Proposal for Aspen Center for Physics Summer 2008 Program Title: “Bacteria Meet Physics” Organizers: Ned Wingreen* Michael Laub [email protected] [email protected] (609) 258-8476 (office) (617) 324-0418 (office) (609) 258-8616 (fax) (617) 253-8699 (fax) Department of Molecular Biology Department of Biology Princeton University Massachusetts Institute of Technology KC Huang [email protected] (609) 258-8699 (office) (609) 258-8616 (fax) Department of Molecular Biology Princeton University *Wingreen is the contact person and organizer responsible for ensuring diversity in the pool of applicants. Description and Justification: Rapid technical progress and recent discoveries in molecular biology have brought biologists face-to-face with the importance and challenge of understanding emergent physical phenomena in living cells. Nowhere is this more evident than in the study of bacteria, where fast generation times, tractable genetic systems, a wealth of biochemical probes, novel imaging approaches, and the availability of complete genomes for hundreds of species have allowed dramatic progress in characterizing cellular components and their basic interactions. However, biologists have found that this characterization is generally inadequate to formulate a full understanding of cellular processes. This “understanding gap” points to the presence in cells of biophysical phenomena, often subtle and complex, that emerge from the multiple interactions of cellular components. Over evolutionary time, cells have exploited and interwoven these biophysical effects to optimize the function of their systems. For physicists, helping biologists to understand how cells use physics is not only a challenge but also an opportunity: billions of years of “experiments” in biophysics are packed into every cell. Some of the most promising areas of collaboration between physicists and bacteriologists include: • Intracellular organization and dynamics – Due in large part to recent advances in fluorescence microscopy of living cells, the interiors of bacteria have been revealed to be complexly organized, with proteins localized to one or both poles, to midcell, or in helices spanning all or part of the cell’s length. Moreover, localization patterns are highly dynamic, e.g. the regulation of cell division by the Min proteins of cell division via a Turing instability. The biological functions governed by these dynamic processes include cell division, motility, cell growth, and the determination of cell shape [de Boer; Theriot; Gitai], and many follow as yet unknown physical rules. • Cell-to-cell variability and noise – Single-cell microscopy has also revealed startling variability among genetically identical cells. Noise in gene expression has been implicated in this cell-to-cell variation, and physicists have been leaders in measuring noise (down to the level of single molecules), modeling noise propagation, understanding the origins of noise, and exploring its consequences, including stochastic cell-fate determination (e.g. competence in B. subtilis) and maintenance of phenotypic variation in clonal populations [Golding; Xiao; Elowitz]. • Signaling, networks, and design principles – A general paradigm in biology is that “form is function,” but we are only beginning to understand how the architecture of intracellular networks reflects their biological function. Architectures of signaling systems (e.g. quorum sensing, chemotaxis), gene regulation (e.g. transcription factors, small RNAs), metabolic and other networks are often complex and multiply connected by feedbacks. Only with a combined understanding of the relevant biology, the emergent biophysical phenomena, and the underlying engineering principles is the logic of these systems likely to be revealed [Bassler; Cluzel; Goulian; Sourjik]. Many of the leading biologists working in these areas appreciate the need for strong interactions with physicists and theorists to bridge the understanding gap. Moreover, the opportunity to simultaneously discover new physical phenomena and to solve outstanding problems in biology has attracted the interest of a broad group of quantitative scientists, including physicists of varied backgrounds, many of whom are likely to attend the program. Each topic will be used as a launch pad for one week of talks and discussion, which will include a speaker who addresses how the evolutionary development of the bacterial system informs our current understanding of the physical mechanisms at work. Past workshops, such as the “Physics Inspired by Biology” Program from Summer 2006, had great success utilizing experimental talks to foster broad communication among the entire group. Therefore, after initial Monday morning sessions of 5-minute talks by each new participant, the program will comprise a few in-depth talks by experimentalists to initiate discussion of emergent physical phenomena in bacteria. Our goal in bringing experimentalists and theorists together is twofold: to encourage new theoretical models and to inspire novel quantitative and physically motivated experiments. In order for participants to engage deeply in the subjects, while allowing time for informal discussions, we propose a four-week workshop, where the additional week will provide further opportunities to focus on specific biological problems that have inspired the most discussion. Schedule: The preferred time for the workshop is August, with the additional possibility of organizing the workshop in late June and early July. All of the organizers are available during these periods. The first two weeks of June are undesirable due to conflict with the American Society of Microbiology General Meeting in Boston from June 1st-5th. July is undesirable due to overlap with the annual Biophysics school at the Boulder School for Condensed Matter and Materials Physics. Scheduling our Aspen workshop in August will increase international participation since many of our colleagues in soft condensed matter physics and biophysics will already have plans to be nearby in Boulder in July. Participants: Our colleagues met the proposed program with great enthusiasm, with multiple theorists and experimentalists from all of the general research areas discussed above likely to attend. The participants listed below have already committed to apply for the workshop, and form a diverse group of scientists from a variety of disciplines, departments, and (international) institutions, whose interaction is likely to substantially increase our understanding of emergent physical phenomena in bacterial systems. • Uri Alon (Weizmann, Physics) • Naama Barkai (Weizmann, Physics) • Bonnie Bassler (Princeton, Molecular Biology) • Bill Bialek (Princeton, Physics) • Philippe Cluzel (Univ. Chicago, Physics) • Hilary Coller (Princeton University, Molecular Biology) • Piet de Boer (Case Western Univ., Molecular Biology) • Jonathan Eisen (UC Davis, Microbial Genomics) • Daniel Fisher (Harvard, Physics) • Zemer Gitai (Princeton, Molecular Biology) • Ido Golding (UIUC, Physics) • Mark Goulian (Univ. Pennsylvania, Physics) • Terry Hwa (UCSD, Physics) • Leonid Kruglyak (Princeton, Evolutionary Biology) • Rich Lenski (Michigan State Univ., Microbiology) • Yigal Meir (Ben Gurion Univ., Physics) • Coleen Murphy (Princeton, Molecular Biology) • Erin O’Shea (Harvard, Biology) • Rob Phillips (Caltech, Applied Physics) • Sima Setayeshgar (Indiana, Physics) • Josh Shaevitz (Princeton, Physics) • Victor Sourjik (Heidelberg, Molecular Biology) • Chao Tang (UCSF, Systems Biology) • Yuhai Tu (IBM) • Doug Weibel (Wisconsin, Biochemistry) • Jie Xiao (Johns Hopkins School of Medicine, Biophysics) The following is a list of other potential participants whose work would also complement the workshop program. • Michael Elowitz (Caltech, Applied Physics) • Hana El-Samad (UCSF, Systems Biology) • Alan Grossman (MIT, Biology) • W. E. Moerner (Stanford, Chemistry) • Boris Shraiman (UCSB, KITP) • Julie Theriot (Stanford, Biochemistry) • Alexander van Oudenaarden (MIT, Physics) Each organizer has read and approved this proposal. Ned Wingreen KC Huang Michael Laub .
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