 Magdalene So, PhD
Professor
Contact Information:
Education:
- University of Washington, 1976
Research:
TYPE IV PILI, MICROBES AND DISEASE
Microbes have evolved numerous mechanisms to adapt to, and co-exist with, their human host. Our goal is to define these mechanisms in molecular terms, and to understand how they influence the genesis of disease. We focus on two microbial pathogens, Neisseria gonorrhoeae and Neisseria meningitidis, and the role Type IV pili play in infection. We use cell biology, biochemistry and biophysics approaches to identify the bacteria-host interactions driven by Type IV pili, and the biological consequences that result from them. This information will allow us to identify new drug and vaccine targets and contribute to our general knowledge of microbial pathogenesis. Type IV pili are filamentous surface structures expressed by many pathogenic and free-living bacteria. The pilus fiber is a dynamic structure that undergoes cycles of extension, substrate tethering and retraction. Multiple pili on the same cell engaging in this process powers twitching motility (crawling over surfaces). Pilus retraction also enables bacteria to take up exogenous DNA (a form of genetic exchange), to engage in biofilm formation and quorum sensing, and, in the case of some pathogens, to attach to host cells. In the case of Neisseria, the physical force of pilus retraction transduced into the infected cell activates stress-responsive cascades, reorganizes host cell cortical structures, and dampens apoptosis signaling. These responses serve to promote infection with minimum damage to the host. |
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CLICK HERE to watch a movie of pilus retraction and read more about: Type IV pili Forces generated by retracting pili How epithelial cells respond to pilus retraction force Type IV pilus signaling through CD46 Commensal Neisseria Lab members and collaborators Lab publications and other reading material |
Publications:
Biomechanics/Dynamics
- Biais N, Ladoux B, Higashi DL, So M and Sheetz M. Cooperative retraction of bundled Type IV pili enables nanonewton force generation. PLoS Biol. 6:e87, 2008.
- Higashi DL, Lee SW, Snyder A, Weyand NJ, Bakke A and So M. Dynamics of Neisseria gonorrhoeae Attachment: Microcolony Development, Cortical Plaque Formation and Cytoprotection, Infect. Immun. 75:4743-4753, 2007.
Pilus retraction and host cell signaling
- Howie H, Shiflett and So M. ERK mediated downregulation of Bim and Bad during infection with N. gonorrhoeae. Infect Immun. 76:2715-2721, 2008.
- Weyand N, Lee SW, Higashi DL, Cawley D, Yoshihara P and So M. Monoclonal antibody detection of CD46 clustering beneath Neisseria gonorrhoeae microcolonies. Infect Immun. 74:2428-2435, 2006.
- Howie HL, Glogauer M and So M. N. gonorrhoeae Type IV pilus stimulates mechanosensitive pathways and cytoprotection through a pilT-dependent mechanism. PLoS Biol. 4:e100, 2005.
Peer-reviewed publications
Click here to see a listing of Peer-reviewed publications
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