RESEARCH

the bennett lab studies broad aspects of fungal biology, including genetic and epigenetic mechanisms of phenotypic variation and their impact on commensalism and pathogenesis.

The lab has a long-standing interest in the sexual cycles of Candida species that are important human fungal pathogens.  This has led to the identification of unusual or specialized mating cycles in Candida.  Our studies led to the identification of same-sex mating in Candida albicans.  This species lacks meiosis and instead undergoes a program of concerted chromosome loss (CCL) to complete a ‘parasexual’ cycle.

 

Several Candida species are known to undergo “phenotypic switching”, in which cells exhibit heritable and reversible transitions between different cell states.  This is best exemplified by the white-opaque switch in C. albicans.  The mechanism of white-opaque switching involves rewiring of transcriptional networks in combination with changes in histone modifications.  Analysis of the switch can provide fundamental insights into how eukaryotic cells undergo differentiation.

 

 

Most pathogenic Candida are diploid species that show extensive plasticity due to a variety of mutational and recombinational processes.  We study C. albicans genomes from clinical isolates to identify genetic loci responsible for differences in clinically-relevant traits.  We also perform experimental evolution experiments in which C. albicans strains are passaged and re-sequenced to determine how the genome changes over short time scales, and how this influences interactions with the host. 

In addition to epigenetic mechanisms, our studies reveal that high-frequency genetic events can increase phenotypic variation in C. albicans.  For example, the “white-to-gray” switch occurs in diploid strains that are naturally heterozygous (+/-) for a key transcription factor.  Loss of heterozygosity events therefore produce a null mutant (the gray phenotype).  Formation of the gray state also results in increased fitness in gastrointestinal models of commensal infection.

Candida species are both common components of the human microbiome and important opportunistic pathogens.  We investigate how the genetic and epigenetic mechanisms shown above impact processes relevant to commensal and pathogenic forms of infection in C. albicans and related Candida species.