个人简介

Born Chicago, Illinois, 1972. Harvard University, A.B., 1994, Ph.D., 1999 University of Oxford, 1999-2001. University of California, Berkeley, 2001-2003. University of Chicago, Professor, 2003- Director, James Franck Institute, 2012- Accolades 2008 Alfred P. Sloan Fellow. 2006 NSF CAREER Award. 2005 Searle Scholar. 2003 Dreyfus New Faculty Award. 2000-2001 Linacre College EPA Cephalosporin Junior Research Fellow. 1999 Burroughs Wellcome Fund Hitchings-Elion Postdoctoral Fellow. 1994-1999 Howard Hughes Medical Institute Predoctoral Fellow.

研究领域

Physical Chemistry/Biophysics/Theoretical

My group and I develop and apply theoretical and computational approaches for relating biological behavior to underlying molecular interactions. Our effort is in three broad areas: Physical models of biological systems: Because the defining properties of life (growth, movement, and directed response to environmental stimuli) rely on irreversible energy consumption and dissipation, much of our research centers on the statistics of stochastic systems far from equilibrium. This is an exciting time in this area as basic principles have emerged over the last two decades, and there is now the opportunity to explore how they apply in real systems in order to realize their potential for designing and interpreting experiments. To this end, my group and I are working to develop phenomenological models in close collaboration with researchers acquiring data amenable to quantitative analysis (e.g., cellular images, expression levels, forces). We have worked on cytoskeletal, circadian, and developmental problems in reconstituted systems with purified components, cell lines, bacteria, flies, and mice. Enhanced sampling algorithms: One feature that makes studies of biological behavior challenging is that the relevant dynamics span a hierarchy of time and length scales ranging from Ångstroms and femtoseconds to millimeters and days. Experiments are now beginning to bridge the gaps in spatial and temporal resolution, and models are vital for design and interpretation of such measurements. Corresponding simulations require methods that can increase exploration of states that are rarely visited in comparison with the time scale of molecular fluctuations (e.g., transition states) while still enabling recovery of unbiased statistical averages. We developed some of the most general and efficient methods available for accelerating the convergence of properties of microscopically irreversible models (nonequilibrium umbrella sampling and steered transition path sampling); we are now working with applied mathematicians to analyze these methods rigorously to improve and extend them. Additionally, we are exploring dimensional reduction techniques (i.e., automated methods for identifying physically informative reaction coordinates in complex systems) to aid in interpreting simulations and connecting them with experimental observables. Reverse engineering regulatory networks: Extensive data from high throughput (e.g., genome-wide) experiments are now available for many biological systems, but it remains unclear how best to use this information to formulate mechanistic and predictive models. We introduced, validated, and deployed the first approach for combining binding and expression measurements to identify long-range (in DNA sequence) gene regulatory targets of transcription factor binding events (EMBER: Expectation Maximization of Binding and Expression pRofiles). We continue to investigate methods for integrating diverse types of data for better elucidation of molecular interactions.

近期论文

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Kale, S., Sode, O., Dinner, A. R., & Weare, J. Finding chemical reaction paths with a multilevel preconditioning protocol. J. Chem. Theor. Comp. 10, 5467-5475. Iyer-Biswas, S., Wright, C. S., Henry, J. T., Lo, K., Burov, S., Crooks, G. E., Crosson, S., Dinner, A. R. & Scherer, N. F. Scaling laws governing stochastic growth and division of single bacterial cells. Proc. Natl. Acad. Sci. USA 111, 15912-15917. Iyer-Biswas, S., Crooks, G. E., Crosson, S., Scherer, N. F. & Dinner, A. R. Universality in stochastic exponential growth. Phys. Rev. Lett. 113, 028101. Mathew, R., Mao, A., Chiang, A. H., Bertozzi-Villa, C., Bunker, J. J., Scanlon, S. T., McDonald, B. D., Constanides, M. G., Hollister, K., Singer, J. D., Dent, A. L., Dinner, A. R. & Bendelac, A. A negative feedback loop mediated by the Bcl6-cullin3 complex limits Tfh differentiation. J. Exp. Med. 211, 1137-1151. Singh, H., Khan, A. A. & Dinner, A. R. Gene regulatory networks in the immune system. Trends Immunol. 35, 211-218. Tempkin, J. O. B., Qi, B., Saunders, M. G., Roux, B., Dinner, A. R. & Weare, J. Using multiscale preconditioning to accelerate the convergence of iterative molecular calculations. J. Chem. Phys. 140, 184114. Saunders, M. G., Tempkin, J., Weare, J., Dinner, A. R., Roux, B. & Voth, G. A. Nucleotide regulation of the structure and dynamics of G-actin. Biophys. J. 106, 1710- 1720. Burov, S., Tabei, S. M. A., Huynh, T., Murrell, M. P., Philipson, L. H., Rice, S. A., Gardel, M. L., Scherer, N. F. & Dinner, A. R. Distribution of directional change as a signature of complex dynamics. Proc. Natl. Acad. Sci. USA 110, 19689-19694. Xu, X., Rice, S. A. & Dinner, A. R. Influence of interlayer exchanges on vorticity-aligned colloidal string assembly in a simple shear flow. J. Phys. Chem. Lett. 4, 3310-3315. Dama, J. F., Sinitskiy, A. V., McCullagh, M., Weare, J., Roux, B., Dinner, A. R. & Voth, G. A. The theory of ultra coarse-graining. I. General principles. J. Chem. Theor. Comp. 9, 2466-2480. Ochiai, K., Maienschein-Cline, M., Simonetti, G., Chen, J., Rosenthal, R., Brink, R., Chong, A. S., Klein, U., Dinner, A. R., Singh, H. & Sciammas, R. Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4. Immunity 38, 1-12. Tabei, S. M. A., Burov, S., Kim, H. Y., Kuznetsov, A., Huynh, T., Jureller, J., Philipson, L. H., Dinner, A. R. & Scherer, N. F. Intracellular transport of insulin granules is a subordinated random walk. Proc. Natl. Acad. Sci. USA 110, 4911-4916. Guttenberg, N., Dama, J. F., Saunders, M. G., Voth, G. A., Weare, J. & Dinner, A. R. Minimizing memory as an objective for coarse-graining. J. Chem. Phys. 138, 094111. Xu, X., Rice, S. A. & Dinner, A. R. Relation between ordering and shear thinning in colloidal suspensions. Proc. Natl. Acad. Sci. USA 110, 3771-3776. Lin, Y., Li, Y., Crosson, S., Dinner, A. R. & Scherer, N. F. Phase resetting reveals network dynamics underlying a bacterial cell cycle. PLoS Comp. Biol. 8, e1002778. Maienschein-Cline, M., Dinner, A. R., Hlavacek, W. S. & Mu, F. Improved predictions of transcription factor binding sites using physicochemical features of DNA. Nuc. Acid Res. Advance Access. Pesic, J., Xu, X., Terdik, J. Z., Lopez, A., Rice, S. A., Dinner, A. R. & Scherer, N. F. Structural responses of quasi-two-dimensional colloidal fluids to excitations elicited by nonequilibrium perturbations. Phys. Rev. E, 86, 031403. Guttenberg, N., Dinner, A. R. & Weare, J. Steered transition path sampling. J. Chem. Phys. 136, 234103. Yi, C., Chen, B., Qi, B., Zhang, W., Jia, G., Zhang, L., Li, C. Q., Dinner, A. R., Yang, C.-G. & He, C. Duplex interrogation by a direct DNA repair protein in search of base damage. Nature Struct. Mol. Biol. 19, 671-676. Lenz, M., Thoresen, T., Gardel, M. L. & Dinner, A. R. F-actin buckling underlies the contraction of non-sarcomeric actomyosin bundles. Phys. Rev. Lett. 108, 238107. Lenz, M., Gardel, M. L. & Dinner, A. R. Requirements for contractility in disordered cytoskeletal bundles. New J. Phys. 14, 033037. Ochiai, K., Maienschein-Cline, M., Mandal, M., Triggs, J., Bertolino, E., Sciammas, R., Dinner, A. R., Clark, M. R. & Singh, H. A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation. Nature Immunol. 13, 300-307. Maienschein-Cline, M., Zhou, J., White, K. P., Sciammas, R. & Dinner, A. R. Discovering transcription factor regulatory targets using gene expression and binding data. Bioinformatics 28, 206-213. Tabei, S. M. A., Li, Y., Weigert, M. & Dinner, A. R. Model for competition from self during passive immunization, with application to broadly neutralizing antibodies for HIV. Vaccine 30, 607-613. Cheng, X., Xu, X., Rice, S. A., Dinner, A. R. & Cohen, I. Assembly of vorticity-aligned hard-sphere colloidal strings in a simple shear flow. Proc. Natl. Acad. Sci. USA 109, 63-67.