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Research Summary
My laboratory is interested in understanding the biology of the human pathogen Candida albicans. C. albicans is a fungal organism that forms part of the normal microflora in the human gastrointestinal tract. However, Candida is also an opportunistic pathogen that can cause mucosal infections in healthy individuals and life-threatening systemic infections in immunocompromised individuals. The focus of the laboratory is to understand how Candida has adapted to life both as a commensal (harmless form) and as a pathogen in humans. To do this we take advantage of the sequenced genome of C. albicans and use a combination of functional genomics and genetics.
In particular, my laboratory is focused on studying the newly identified sexual cycle of Candida albicans. There are a number of interesting aspects to mating in C. albicans, including the role of ‘phenotypic switching’, in which cells can reversibly switch their morphology between specialized forms called ‘white’ and ‘opaque’. While white cells are more virulent in models of systemic infection, only opaque forms are competent to mate. We are currently investigating the idea that this unique adaptation has arisen to allow mating to occur in the hostile environment of the mammalian host.
A second unusual feature of the C. albicans sexual cycle is that while mating occurs efficiently, no meiotic pathway has been identified yet. Meiosis is a conserved process in which DNA replication is followed by two successive DNA divisions, effectively halving the DNA content in the cell. In its place, we have discovered that efficient non-meiotic chromosome loss can be induced in C. albicans, thereby completing a simple sexual cycle in the organism. Both the mechanism of chromosome loss and the role of the sexual cycle in infection of the host are under investigation. For example, one model we are presently testing is that the mixing of chromosomes during the mating cycle generates strains with increased genetic diversity. These new strains could contribute directly to virulence by generating bursts of genetic diversity that aid in fitness in infection.
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Publications
Bennett, RJ, and Johnson, AD (2006) The role of nutrient regulation and the Gpa2 protein in the mating pheromone response of C. albicans. Mol. Microbiol. 62: 100-119.
Bennett RJ, Johnson AD, Mating in Candida albicans and the Search for a Sexual Cycle. Annu Rev Microbiol. 2005 May 23.
Bennett RJ, Miller MG, Chua PR, Maxon ME, Johnson AD. Nuclear fusion occurs during mating in Candida albicans and is dependent on the KAR3 gene. Mol Microbiol. 2005 Feb;55(4):1046-59.
Bennett RJ, Keck JL. Structure and function of RecQ DNA helicases.Crit Rev Biochem Mol Biol. 2004 Mar-Apr;39(2):79-97. Review.
Bennett RJ, Uhl MA, Miller MG, Johnson AD. Identification and characterization of a Candida albicans mating pheromone. Mol Cell Biol. 2003 Nov;23(22):8189-201.
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Lab Members
Dana Schaefer, Research Assistant
Kevin Alby, Pathobiology Graduate Student
Kim Sherwood, MCB Graduate Student
Suzanne Gilman, Undergraduate Student
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