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Mentor: Alexander Horswill, PhD
Undergraduate Institution: Bemidji State University
Year Entered Into Program: 2009-2010
Research in the Horswill laboratory is focused on a variety of aspects of the bacterial pathogen Staphylococcus aureus. My research includes studying the S. aureus two-component system sae, which is involved in regulating the expression of secreted virulence factors including α-toxin and nuclease. Two-component systems are a signal transduction system typically composed of a sensor kinase, located in the membrane of the cell, and a response regulator, which binds DNA and alters gene expression profiles.
My main project centers on understanding the molecular mechanism of activation of the sae two-component system. At this time I am focusing on the sensing domain of the sensor kinase and am using a mutagenesis approach to identify residues that are important for activation of the sensor. Unfortunately, the exact signal required to activate the sae system is unknown, but activation of the system results in a substantial upregulation of two genes encoded directly upstream of and co-transcribed with the two-component system machinery. Both of these proteins have unknown structures and functions. I am currently investigating the structure and function of these two proteins, as well as their contribution to the activation of the sae system and potential interactions with the sensor kinase.
Kirchdoerfer RN, Garner AL, Flack CE, Mee JM, Horswill AR, Janda KD, Kaufmann GF, Wilson IA. Structural basis for ligand recognition and discrimination of a quorum-quenching antibody. J Biol Chem. 2011 May 13;286(19):17351-8. PMID: 21454495.
Thoendel M, Kavanaugh JS, Flack CE, Horswill AR. Peptide signaling in the staphylococci. Chem Rev. 2011 Jan 12;111(1):117-51. Review. PMID: 21174435.
McKean JP, Koopmans LVC, Flack CE, Fassnacht CD, Thompson D, Matthews K, Blandford RD, Readhead ACS, Soifer BT. High resolution imaging of the anomalous flux-ratio gravitational lens system CLASS B2045+265: Dark or luminous satellites? Mon. Not. R. Astron. Soc. 2007 Mar 16;378, 109–118.
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