Molecular Biology of Evolution
The gradual rewiring of transcriptional circuits over evolutionary timescales is a major source of the diversity of life on the planet. We study the molecular mechanisms that underlie these rewiring events to understand what it is about transcription circuits that make them highly evolvable. We also study how such changes in circuitry lead to differences in appearance and behavior among species.
We carry out this work in a large group of unicellular eukaryotes including the model eukaryote Saccharomyces cerevisiae and the human fungal pathogen Candida albicans. These organisms are approximately as divergent as fish and humans, and we have documented major differences in their transcriptional circuitries. We study the molecular mechanisms through which these changes have occurred and how potential fitness barriers were traversed during these transitions.
Molecular Biology of Candida albicans
C. albicans is a species of fungus that typically resides asymptomatically in the gastrointestinal tracts of humans and other warm-blooded animals. It is also the most prevalent human fungal pathogen, causing a variety of skin and soft tissue infections in healthy people and more virulent and invasive and disseminated diseases in immunocompromised humans. We study the specific features of C. albicans that allow it to survive in a human mammalian host and to cause disease and how these features evolved under the selective pressure of the host. We study how C. albicans forms biofilms, how it interacts with host cells, how it interacts with other members of the human microflora, and how its transcription circuits and RNA splicing patterns have adapted it for the host.
We are especially interested in a process called white-opaque switching, which appears key to C. albicans’ ability to thrive in a mammalian host. Switching is epigenetic, producing two distinct types of cells from the same genome; each cell-type is heritable for many generations, and they differ in their appearance, the genes they express, and the host tissues they are most suited for. We study the switching mechanism, as well as the specializations of the two cell types produced from it.