Genomic Interrogation and Perturbation of Natural Fungal-Host Cell Surface Dynamics

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Candida is a clinically important fungal pathogen disproportionately affecting immunocompromised patients. The fungal-immune interface is complex and dynamic, and understanding how this interaction surface changes over time in vivo will require both reductionist and genome-wide interrogation. Focusing on the fungal ligand β-glucan and its innate immune receptor Dectin-1, this research project exploits functional genomics tools on both sides of the fungal-host equation and utilizes model organisms to elucidate key modulators of immunity and virulence. Genome-wide screening in fungi will be used to identify evolutionarily conserved fungal gene networks that regulate immune response and are targetable by novel therapeutics. In a complementary way, a top-down unbiased genetic screen in innate immune cells will be utilized along with a bottom-up reconstitution assay to identify immune components that are necessary and sufficient for altering immune recognition and response. Finally, monitoring infection dynamics in vivo will place all of this information in context and fill the current gap in knowledge between in vitro dynamics and survival of experimental infection.

Recent Publications and Presentations

  • Wheeler RT “Dynamics of Candida-host interaction in vivo,” American Society for Microbiology, General Meeting; San Diego, CA, May 2010.
  • Wheeler RT, “The changing face of C. albicans during infection,” Candida and Candidiasis 2010; Miami, FL, March, 2010.
  • Moxley J.F., Jewett M.C., Antoniewicz M.R., Villas-Boas S.G., Alper H., Wheeler R.T., Tong L., Hinnebusch A.G., Ideker T., Nielsen J., Stephanopoulos G. (2009) Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p. Proc Natl Acad Sci U S A. 2009 106(16):6477-82. PubMed PMID: 19346491; PubMed Central PMCID: PMC2672541.
  • Wheeler RT, “Dynamics of fungal-host interaction during infection,” New England Biolabs; Ipswich, MA; December 2009.
  • Wheeler RT, “The dynamics of fungal-immune interaction: M&Ms and macrophages,” Worcester Polytechnic Institute, Department of Biology and Biotechnology; Worcester, MA; September 2009.
  • Wheeler RT, “The changing face of C. albicans during infection,” Microbial Pathogenesis & Host Response; Cold Spring Harbor Laboratory, NY; September 2009.