Collins, Sean - University of California, Davis - College of Biological Sciences

研究领域

Signal Transduction Controlling Cell Motility Our lab is interested in how individual cells process information, make decisions, and enact appropriate responses. This often requires using molecular components to achieve properties such as adaptation, sensitivity, and spatial processing of signals. As a favorite model system, we study how human neutrophils process dynamic extracellular chemical cues to guide their behavior. In order to chase a pathogen or migrate to a site of infection, a neutrophil must overcome challenges of breaking symmetry, generating stable cell polarity, and responding to spatial gradients of signaling molecules. The neutrophil response needs to be highly sensitive and decisive so that it can generate polarity, reorganize its cytoskeleton, and move, even if the input signal is weak or provides little spatial information. Additionally, in order to orient itself towards the highest concentration of the chemical attractant, the cell needs to compare input levels across space. We still know very little about how cells balance these goals or about the mechanisms that enable spatial processing. To tackle these questions, we use a combination of techniques with particular emphasis on systematic quantitative analysis of genetic perturbations, direct monitoring of signaling using live-cell imaging of fluorescent biosensors, and mathematical modeling.

近期论文

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Winans AM, Collins SR, Meyer T. 2016. Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation. Elife 5:12387. Yang HW*, Collins SR*, Meyer T. 2016. Locally excitable Cdc42 signals steer cells during chemotaxis. Nat Cell Biol 18(2):191-201. Collins SR, Yang HW, Bonger KM, Guignet EG, Wandless TJ, Meyer T. 2015. Using light to shape chemical gradients for parallel and automated analysis of chemotaxis. Mol Syst Biol 11(4):804. Dey G, Jaimovich A, Collins SR, Seki A, Meyer T. 2015. Systematic discovery of human gene function and principles of modular organization through phylogenetic profiling. Cell Rep 10(6):993-1006. Galic M, Tsai FC, Collins SR, Matis M, Bandara S, Meyer T. 2014. Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons. Elife 3:e03116. Martín GM, King DA, Green EM, Garcia-Nieto PE, Alexander R, Collins SR, Krogan NJ, Gozani OP, Morrison AJ. 2014. Set5 and Set1 cooperate to repress gene expression at telomeres and retrotransposons. Epigenetics 9(4):513-22 Frost A, Elgort MG, Brandman O, Ives C, Collins SR, Miller-Vedam L, Weibezahn J, Hein MY, Poser I, Mann M, Hyman AA, Weissman JS. 2012. Functional repurposing revealed by comparing S. pombe and S. cerevisiae genetic interactions. Cell 149(6):1339-52 Ryan CJ, Roguev A, Patrick K, Xu J, Jahari H, Tong Z, Beltrao P, Shales M, Qu H, Collins SR, Kliegman JI, Jiang L, Kuo D, Tosti E, Kim HS, Edelmann W, Keogh MC, Greene D, Tang C, Cunningham P, Shokat KM, Cagney G, Svensson JP, Guthrie C, Espenshade PJ, Ideker T, Krogan NJ. 2012. Hierarchical modularity and the evolution of genetic interactomes across species. Mol Cell 46(5):691-704 Hoppins S*, Collins SR*, Cassidy-Stone A, Hummel E, Devay RM, Lackner LL, Westermann B, Schuldiner M, Weissman JS, Nunnari J. 2011. A mitochondrial-focused genetic interaction map reveals a scaffold-like complex required for inner membrane organization in mitochondria. J Cell Biol 195(2)323-40 Charles GM, Chen C, Shih SC, Collins SR, Beltrao P, Zhang X, Sharma T, Tan S, Burlingame AL, Krogan NJ, Madhani HD, Narlikar GJ. 2011. Site-specific acetylation mark on an essential chromatin-remodeling complex promotes resistance to replication stress. Proc Natl Acad Sci U S A 108(26):10620-5 Collins SR, Meyer T. 2011. Evolutionary origins of STIM1 and STIM2 within ancient Ca2+ signaling systems. Trends Cell Biol 21(4):202-11 Collins SR, Roguev A, Krogan NJ. 2010. Quantitative genetic interaction mapping using the E-MAP approach. Methods Enzymol 470:205-31 Collins S, Meyer T. 2010. Cell biology: A sensor for calcium uptake. Nature 467(7313):283 Breslow DK, Collins SR, Bodenmiller B, Aebersold R, Simons K, Shevchenko A, Ejsing CS, Weissman JS. 2010. Orm family proteins mediate sphingolipid homeostasis. Nature 463(7284):1048-53 Collins SR, Weissman JS, Krogan NJ. 2009. From information to knowledge: new technologies for defining gene function. Nat Methods 6(10):721-23 Kornmann B, Currie E, Collins SR, Schuldiner M, Nunnari J, Weissman JS, Walter P. 2009 An ER-mitochondria tethering complex revealed by a synthetic biology screen. Science 325(5939):477-81 [Epub 2009 Jun 25] Jonikas MC, Collins SR, Denic V, Oh E, Quan EM, Schmid V, Weibezahn J, Schwappach B, Walter P, Weissman JS, Schuldiner M. 2009. Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum. Science 323(5922): 1693-7 Fiedler D, Braberg H, Mehta M, Chechik G, Cagney G, Mukherjee P, Silva AC, Shales M, Collins SR, van Wageningen S, Kemmeren P, Holstege FC, Weissman JS, Keogh MC, Koller D, Shokat KM, Krogan NJ. 2009. Functional organization of the S. cerevisiae phosphorylation network. Cell 136(5):952-63 Collins SR, Meyer T. 2009. Calcium flickers lighting the way in chemotaxis? Dev Cell 16(2):160-1 Wang H, Kakaradov B, Collins SR, Karotki L, Fiedler D, Shales M, Shokat KM, Walther TC, Krogan NJ, Koller D. 2009. A complex-based reconstruction of the Saccharomyces cerevisiae interactome. Mol Cell Proteomics 8(6):1361-81 [Epub 2009 Jan 27] Wilmes GM, Bergkessel M, Bandyopadhyay S, Shales M, Braberg H, Cagney G, Collins SR, Whitworth GB, Kress TL, Weissman JS, Ideker T, Guthrie C, Krogan NJ. 2008. A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing. Mol Cell 32(5):735-46 Roguev A, Bandyopadhyay S, Zofall M, Zhang K, Fischer T, Collins SR, Qu H, Shales M, Park HO, Hayles J, Hoe KL, Kim DU, Ideker T, Grewal SI, Weissman JS, Krogan NJ. 2008. Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast. Science 322:405-10 Typas A, Nichols RJ, Siegele DA, Shales M, Collins SR, Lim B, Braberg H, Yamamoto N, Takeuchi R, Wanner BL, Mori H, Weissman JS, Krogan NJ, Gross CA. 2008. High-throughput, quantitative analyses of genetic interactions in E. coli. Nat Methods 5(9):781-7 Breslow DK, Cameron DM, Collins SR, Schuldiner M, Stewart-Ornstein J, Newman HW, Braun S, Madhani HD, Krogan NJ, Weissman JS. 2008. A comprehensive strategy enabling high-resolution functional analysis of the yeast genome. Nat Methods 5:711-8 Feng BY, Toyama BH, Wille H, Colby DW, Collins SR, May BC, Prusiner SB, Weissman J, Shoichet BK. 2008. Small-molecule aggregates inhibit amyloid polymerization. Nat Chem Biol 4:197-9