Alexander-Sandy Johnson, PhD

Professor & Vice Chair
Department of Microbiology and Immunology
+1 415 476-8783
Research Overview: 
  1. 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 (the fungi) including the "model" eucaryoteSaccharomyces 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.
  2. 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.
Primary Thematic Area: 
Virology & Microbial Pathogenesis
Secondary Thematic Area: 
Human Genetics
Research Summary: 
Microbial Evolution and Pathogenesis

Websites

Publications: 

A population shift between two heritable cell types of the pathogen Candida albicans is based both on switching and selective proliferation.

Proceedings of the National Academy of Sciences of the United States of America

Dalal CK, Zuleta IA, Lohse MB, Zordan RE, El-Samad H, Johnson AD

Genetic Modification of Closely Related Candida Species.

Frontiers in microbiology

Mancera E, Frazer C, Porman AM, Ruiz-Castro S, Johnson AD, Bennett RJ

Intrinsic cooperativity potentiates parallel cis-regulatory evolution.

eLife

Sorrells TR, Johnson AN, Howard CJ, Britton CS, Fowler KR, Feigerle JT, Weil PA, Johnson AD