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个人简介

2015 - NIH K22 Career Transition Award 2012 - NIH F32 Fellowship

研究领域

My lab explores how mechanical forces regulate bacterial responses using an approach that combines techniques from biophysics, molecular biology, genetics, fluid mechanics, and computational modeling. The fundamental questions that we explore are: 1. What is the effect of mechanical forces on bacterial physiology, 2. What signaling mechanisms do bacteria use to detect and transduce mechanical stimuli, and 3. How do mechanical forces affect population-level behaviors such as biofilm development and pathogenesis? Bacteria encounter a variety of mechanical forces during infection and in natural environments including shear stress, tension, and compression forces. However, the role of these forces in pathogenesis and their effects on cell physiology are not understood. We have discovered that attachment to surfaces activates virulence in the bacterium Pseudomonas aeruginosa, a broad range opportunistic pathogen, and have identified PilY1 as a putative mechano-sensitive protein that is required for virulence activation. Our work suggests that bacteria detect their hosts (and know when to infect) based on detection of a rigid surface and on the pattern of shear stress. In addition, bacteria appear to detect different types of mechanical forces such as shear stress using distinct mechano-transduction systems. We are detailing these mechanisms of mechano-sensation in bacteria, understanding how these pathways regulate pathogenesis and other behaviors at the single-cell and population scales, and identifying the mechanical conditions that stimulate bacterial infection. Understanding the mechano-responses of P. aeruginosa will enable us to control bacterial populations, changing the bias in polymicrobial populations and microbiomes against pathogens and in favor of commensals by manipulating mechanics of the environment.

近期论文

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Persat, A., C.D. Nadell, M.K. Kim, F. Ingremeau, A. Siryaporn, N.S. Wingreen, B.L. Bassler, Z. Gitai, H.A. Stone, (2015) The Mechanical World of Bacteria. Cell, 161(5): 988-997. Siryaporn, A., M. Y. Kim, Y. Shen, H. Stone & Z. Gitai, (2015) Colonization, competition and dispersal of pathogens in fluid flow networks. Current Biology, 25(9): 1201-1207. Miller, L.C., C.T. O’Loughlin, Z. Zhang, A. Siryaporn, B. Bassler & M. Semmelhack, (2015) Development of potent inhibitors of pyocyanin production in Pseudomonas aeruginosa. J. Med. Chem. 58(3):1298-1306. Siryaporn, A., S. L. Kuchma, G. A. O’Toole & Z. Gitai, (2014) Surface attachment induces P. aeruginosa virulence. PNAS 111(47): 16860-16865. Highlighted in Ellison C & Y. Brun, (2014) Mechanosensing: A Regulation Sensation, Current Biology 25(3):R113-R115. Cowles, K .N., T. S. Moser, A. Siryaporn, N. Nyakudarika, W. Dixon, J. J. Turner, and Z. Gitai, (2013) The putative Poc complex controls two distinct Pseudomonas aeruginosa polar motility mechanisms. Mol Microbiol 90(5): 923-938. O’Loughlin, C.T., L. C. Miller, A. Siryaporn, K. Drescher, M. Semmelhack & B. Bassler, (2013) A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. PNAS 110(44): 17981-6. Highlighted in Kåhrström CT, (2013) Antimicrobials: Silencing bacterial communication, Nature Reviews Microbiology 11(12): 820-821. Shen, Y.*, A. Siryaporn, S. Lecuyer, Z. Gitai & H. Stone, (2012) Flow Directs Surface-Attached Bacteria to Twitch Upstream. Biophys J 103(1): 146-151. Bakshi, S., A. Siryaporn, M. Goulian & J.C. Weisshaar, (2012) Superresolution Imaging of Ribosomes and RNA Polymerase in Live Escherichia coli Cells. Mol Microbiol 85(1): 21-38.

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