The ability to polarize is found in nearly all cell types and is essential for physiological processes as diverse as cell differentiation, cell motility, neuronal growth, and immune responses. Polarization can occur either in response to an internal or external spatial signal, or spontaneously in the apparent absence of pre-existing spatial cues. Interestingly, many mechanisms leading to polarization, such as those involving actin- and scaffolding-dependent feedback, appear to be conserved across a broad range of cell types. We currently lack a quantitative understanding of how these different mechanisms work together to create sharply defined spatial patterns, analogous to MAP-kinase cascades creating ultra-sensitive temporal switches. We are working to dissect, disentangle, and reassemble mechanisms of polarization in the yeast budding and neutrophil chemotaxis pathways, using a close collaboration between modeling and experimentation. The mathematical tools we use to study polarity formation and maintenance draw upon theory from reaction-diffusion equations, geometry, and stochastic processes. Validation of model predictions require the development of automated image processing algorithms and analytical techniques to extract information from movies of polarizing yeast and fast-moving neutrophils.
RESEARCH INTERESTS
Cytological profiling
Cell polarity
Systems biology
RECENT PUBLICATIONS
Marco, E., Wedlich-Soldner, R., Li, R., Altschuler, S.J., Wu, L.F., "Endocytosis optimizes the dynamic localization of membrane proteins that regulate cortical polarity" Cell, 129:411-22, April 2007
Loo, L.H., Wu, L., Altschuler, S.J., "Image-based multivariate profiling of drug responses from single cells" Nature Methods, 2007:445-53, May 2007
Maciag, K., Altschuler, S.J., Slack, M.D., Krogan, N.J., Emili, A., Greenblatt, J.F., Maniatis, T., Wu, L.F., "Systems-level analyses identify extensive coupling among gene expression machines" Molecular Systems Biology, 2006:msb400045-E1-msb400045-E14, January 2006
Wedlich-Soldner, R., Altschuler, S.J., Wu, L.F., Li, R., "Spontaneous cell polarization through actomyosin-based delivery of the Cdc42 GTPase." Science, 299(5610):1231-1235, 2003
SIGNIFICANT PUBLICATIONS
Marco, E., Wedlich-Soldner, R., Li, R., Altschuler, S.J., Wu, L.F., "Endocytosis optimizes the dynamic localization of membrane proteins that regulate cortical polarity" Cell, 129:411-422, April 2007
Wedlich-Soldner, R., Altschuler, S.J., Wu, L.F., Li, R., "Spontaneous cell polarization through actomyosin-based delivery of the Cdc42 GTPase." Science, 299(5610):1231-1235, 2003
Wu, L.F., Hughes, T.R., Davierwala, A.P., Robinson, M.D., Stoughton, R., Altschuler, S.J., "Large-scale prediction of Saccharomyces cerevisiae gene function using overlapping transcriptional clusters." Nature Genetics, 31(3):255-265, 2002
Acero, A., Altschuler, S.J., Wu, L.F., "Speech/Noise Separation Using Two Microphones and a VQ Model of Speech Signals." Proceedings of the ICSLP, 2002
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