William Courchesne, Ph.D.

Associate Professor
Courchesne
Molecular and cellular biology of calcium metabolism in the yeast, S. cerevisiae

Summary

Professional Biography

  • 1989 - present: Associate Professor, University of Nevada School of Medicine, Microbiology and Immunology Department
    1985 - 1989: Postdoctoral Fellow, University of California, Berkeley

Courses Taught

  • Medical Microbiology for medical students (MICR 601)
  • Medical Microbiology for undergraduates (MICR 300)
  • Microbial Genomics and Genetics (MICR 350)
  • Microbial Pathogenesis (MICR 470/670)
  • Infectious Diseases (MICR 483)
  • Biotechnology Today and Tomorrow (MICR 700)
  • Medical Microbiology for physician assistant students (PAS 620)

Research Interests

Our most recent research has explored the molecular and physiological events involved in transitioning from quiescence to proliferation in the yeast Saccharomyces cerevisiae. The quiescent phase of the cell cycle is of fundamental importance for fungi, yet our understanding of this phase of the cycle is much less well understood than the mitotic cell cycle. We found that the ECM27 gene, which encodes a Na+/Ca2+ exchanger, is responsible for influx of calcium from the extracellular space and release from intracellular stores during membrane stress.

Wild type cells increase total Ca2+ in quiescence but cells lacking ECM27 gene fail to do so and are defective in cell cycle reentry from the quiescent phase. ecm27∆ cells are also defective in maintaining trehalose levels throughout this phase. Addition of high levels of CaCl2 to the growth medium can increase total cellular calcium in ecm27∆ cells during quiescence and can also restore trehalose levels as well as partially restore ability of cells to reenter the mitotic cell cycle. ecm27∆ cells also have altered glycogen levels in exponentially growing cells. Our results show that Ecm27p and Ca2+ play roles in maintaining a high level of trehalose in quiescent cells, which in turn is important in the ability of cells to rapidly return to proliferation.

My lab has also characterized the molecular mechanisms of the antifungal drug amiodarone. We were the first to publish work showing amiodarone has potent antifungal activity against a broad spectrum of fungi and we were the first to publish work showing that amiodarone causes a rise in cytoplasmic calcium in response to alteration of the yeast cell wall. Our work is the first showing effects of this drug, caffeine, and cell wall on calcium ion channels in yeast. UNR holds a patent for use of amiodarone as an antifungal based my research. Published work now shows amiodarone has antiparasitic activity, including an apparent amiodarone cure of a patient with Chagas disease. In addition, , we have synthesized compounds related to amiodarone and tested them for antifungal activity and identified novel antifungal compounds, in a collaboration with Dr. Elizabeth Hejchman, Department of Medical Chemistry, at The Medical University of Warsaw, Poland.

Perhaps the most famous and industrially important characteristic of the yeast Saccharomyces cerevisiae is its ability to produce ethanol as a metabolic product and to survive high concentrations of this toxic compound. We hypothesized that ethanol should induce a Ca2+ influx analogous to other stresses. We have shown a new signaling response elicited by exposure of yeast cells to ethanol, a dramatic rise in the cytoplasmic Ca2+ concentration ([Ca2+]cyt). The ethanol-induced increase in [Ca2+]cyt is largely dependent on the Cch1/Mid1 Ca2+ channel, and affected by cell wall integrity. Our objective is to reveal the functions of the molecular players and physiological conditions involved in this novel signaling process.

Patents

  • Courchesne, W.E., D.A. Schooley, and K.S. Copley. Expression of Proteolytically-Sensitive Peptides of Medical and Agricultural Importance by Yeast. 1998. U.S. Application 60/072,691. Patent rights sold to Novo Nordisk, Inc., 2000.
  • Courchesne, W.E.. Amiodarone as an Antifungal Agent.  Issued 24 April 2001. Patent Number US 6,221,903.

Graduate Students Mentored

  • 2014 - 2015: Rachel Klukovich, M.S., Biotechnology
  • 2011 - 2012: Sara Coffee, M.S., Biology
  • 1996 - 2000: Reva Crump, M.S., CMB
  • 1997 - 1999: Tony Zucca, M.S., CMB
  • 1995 - 1997: Hui Dong, M.S., CMB
  • 1995 - 1997: Bin Sun, M.S., Biochemistry
  • 1994 - 1997: Kathy Copley, Ph.D., Biochemistry
  • 1993 - 1994: Joe Ernaga, M.S., Biology
  • 1992 - 1994: Tatyana Tolkacheva, Ph.D., Center for Bioengineering, Institute of Molecular Biology, Academy of Sciences of the USSR
  • 1991 - 1993: Diane Laudadio, M.S., CMB
  • 1990 - 1994: Robert Archer, Ph.D., CMB

Education

1985 - Ph.D., Microbiology, Massachusetts Institute of Technology
1976 - B.A., Genetics, University of California, Berkeley