Two U of C physics faculty members conduct experimental research in biophysics.
Ph.D., Institut Marie Curie, Paris, 1996.
Assoc. Prof., Dept. Physics, Inst. for Biophysical Dynamics, James Franck Inst., and the College
Experimental biological physics, non-equilibrium systems, biopolymers.
homepage: http://cluzel.uchicago.edu
Noise and information in biological systems. Sudden changes of environment and
life-cycle phases (growth, cell division, and death) characterize the conditions far from
the equilibrium of chemical reactions occurring within individual cells. Yet cells, or more
generally, biological systems, are able to process information accurately and to achieve
precise tasks. How do biological systems use or circumvent these noisy conditions? Most of
the experiments and mathematical models have assumed that the characteristics of the signaling
and chemical reactions occurring within individual cells could be inferred from ensemble measurements.
This approach, however, masks the temporal fluctuations and the dynamics of biological heterogeneous
systems. A more promising alternative is to describe individually and in "real time" these
strongly non-linear (living) systems. By developing novel single-molecule techniques, we can revisit
canonical biological systems and question the advantage of "noise" for inter/intracellular
signaling.
Noise in gene expression in bacteria. When few molecules are involved, chemical reactions
are subject to stochastic fluctuations. Important steps of the gene expression in bacteria can be
modeled by basic chemical reactions. A few molecules in the cell control these reactions.
Consequently, the pattern of protein concentration growth is expected to be highly stochastic,
exhibiting short bursts of variable numbers of proteins at varying time intervals. We are
interested in characterizing experimentally the statistics of those simple chemical reactions
that control the gene expression in individual living cells.
Signaling in chemotaxis. The chemotactic system of E. coli (the network that
governs the migration of bacteria towards chemical attractants) is used as a prototype for the
study of intracellular signal transduction networks. Our approach is to consider the chemotactic
network controlling cellular behavior as a biochemical circuit composed of independent modules.
We identify the modules' contribution to the output within single living cells as well as the
possible sources of their noise.
- Korobkova E., Emonet T., Park H, Cluzel P. Hidden stochastic nature of a single bacterial motor,
Phys. Rev. Letters, 96, 58105 (2006).
- TT, Harlepp S., Guet CC, Dittmar K, Emonet T., Pan T., Cluzel P. Real-time RNA profiling within a single
bacterium, Proc. Natl. Acad. Sci. U S A., 28; 102 (26):9160-4 (2005).
- Korobkova E., Emonet T., Vilar J., Shimizu T. & Cluzel P. From molecular noise to behavioral variability in a single bacterium, Nature, 428, 574-578 (2004.)
- Aldana M and Cluzel P. A natural class of robust networks, Proc Natl Acad Sci U S A. 22;100(15):8710-4 (2003).
- Cluzel P, Surette M, Leibler S. An ultrasensitive bacterial motor revealed by monitoring signaling proteins in single cells, Science 287: 1652-1655 (2000).
- Cluzel P, Lebrun A, Heller C, Lavery R, Chatenay D, Caron F., DNA: An Extensible Molecule, Science 271: 792-794. (1996)
updated 8/2006
 Margaret Gardel
Ph.D., Harvard University, 2004.
Assistant Professor, Dept. Physics, Inst. for Biophysical Dynamics, James Franck Inst., and the College.
Experimental biophysics.
homepage: http://squishycell.uchicago.edu
We are interested in the biological properties of the cytoskeleton of eukaryotic cells and how these regulate cell physiology. Cells generate protrusive and contractile forces in response to external chemical and mechanical stimuli and during cell migration. Improper regulation of the mechanical behavior of cells has been linked to a number of diseases, including asthma, cardiac arrhythmia and cancer metastasis.
The varied mechanical behavior of cells is determined by a dynamic and composite polymer network of > 100 proteins called the cytoskeleton. We develop tools to study the dynamic structure and biophysical behavior of macromolecular assemblies at sub-micron length scales to study how cells generate and transmit mechanical forces.
We use high resolution fluorescence microscopy to observe cytoskeletal protein dynamics in living cells and, simultaneously, measure their biophysical properties at micron length scales. By combining dynamic structure with biophysical measurements, we aim to elucidate the origins of the biophysical behavior of these assemblies. We are particularly interested in the biophysical behavior of contractile actomyosin networks and how these regulate how focal adhesion transmit force to the extracellular matrix.
Cytoskeletal material also provides quite a number of interesting problems in soft condensed matter physics. In contrast to traditional flexible polymers or rigid rods, cytoskeletal polymers are semi-flexible and the energy required to bend the filament on micron length scales is comparable to thermal energy. The competition between enthalpic and entropic effects in the dynamics and deformation of semi-flexible networks lead to extremely rich and varied mechanical response of both entangled solutions and chemically cross-linked networks. In the living cell, these networks are driven far from equilibrium by molecular motors and proteins that regulate filament cross-linking and assembly. We study the mechanical behavior of reconstituted networks of purified cytoskeletal proteins in vitro to better develop physical models of the elasticity of these dynamic semi-flexible polymer networks.
- M.L. Gardel, F. Nakamura, J. Hartwig, J.C. Crocker, T.P. Stossel and D.A. Weitz, Pre-stressed F-actin Networks Cross-linked by Hinged Filamins Replicate Mechanical Properties of Cells, Proceedings of the National Academy of Sciences, 103 1762-1767 (2006).
- M.L. Gardel, F. Nakamura, J. Hartwig, J.C. Crocker, T.P. Stossel and D.A. Weitz, Stress-Dependent Elasticity of Composite Actin Networks as a Model for Cell Behavior, Physical Review Letters, 96 088102 (2006).
- J.H. Shin, M.L. Gardel, F.C. MacKintosh, L Mahadevan, P.A. Matsudaira and D.A. Weitz, Relating Microstructure to Elasticity of Cross-linked and Bundled Actin Networks, Proc. Nat'l Acad. Sci., 101 9637-9641 (2004).
- M.L. Gardel, J.H. Shin, F.C. MacKintosh, L Mahadevan, P.A. Matsudaira and D.A. Weitz, Elastic Behaviors of F-actin Networks, Science, 304 1301-1305 (2004).
- M.L. Gardel, J.H. Shin, F.C. MacKintosh, L Mahadevan, P.A. Matsudaira and D.A. Weitz, Scaling of the Rheology of Prestressed Networks as a Probe of Single Filament Elasticity, Physical Review Letters, 93 188102 (2004).
updated 10/2006
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