Fred Winston, PhD
Department of Genetics, Harvard Medical School
Mechanisms of eukaryotic gene expression in yeast: transcriptional regulation; chromatin structure
Employs yeast as a model organism to study mechanisms of eukaryotic transcriptional regulation.
Capitalize on yeast genetics as well as the structural and functional conservation of transcriptional mechanisms/factors throughout evolution to gain insights into their role in human pathophysiology (for example, HIV infection and cancer).
- Obtain access to a large repository of yeast strains that may be useful for studying gene function; and consult with relevant industries.
- Employ the power of yeast genetics to understand the role of any gene in the transcription process, employing either S. cerevisiae or S. pombe (which is more closely related to mammalian cells).
- Exploit the thousands of different yeast strains available in the Winston laboratory repository to quickly address functional consequences of gene ablation.
- Study mechanisms of environmentally-regulated gene transcription in yeast that may have relevance to disease states, such as hypoxia in cancer
Current Research Interests
Dr. Winston's lab:
- Investigates the interplay of protein factors that operate coordinately to drive transcription.
- Studies chromatin remodeling in the context of transcriptional regulation.
- Elucidates the role of histone gene amplification and the concomitant effects on gene expression.
- Explores the complex signaling initiated by environmental cues, such as oxygen and nitrogen, that serve to modulate transcription.
- Yields insights into functionally conserved transcription factors that may reveal important information for their human orthologs, some of which have been shown to be involved in HIV biology, cancer, and diabetes.
Dr. Winston’s laboratory has a longstanding interest in mechanistic aspects of gene expression/regulation using two yeasts (both S. cerevisiae and S. pombe) as model organisms. His studies employ biochemical and genetic analyses, coupled with functional genomics, to delineate the complex activities of the numerous proteins that are required for coordinated RNA transcription. This laboratory is also focused on chromatin structure, studying modifications of histones and nucleosomes that can calibrate gene expression. Its recent studies have yielded important insights into fundamental aspects of eukaryotic transcription. It has dissected the intricate interplay of the components of the SAGA transcriptional multiprotein complex, whose composition and function are highly conserved throughout evolution. The lab’s studies also have illuminated environmental conditions that impinge upon gene expression, such as oxygen and nitrogen levels.
Other avenues of investigation have delved into various genetic elements that can modulate transcriptional activation. Key findings from these studies include the discovery that specific genes operate to repress the ability of upstream activating sequences (analogous to mammalian enhancer elements) to function at a great distance from the gene promoter, and that non-coding intergenic transcripts, such as the serine-regulated SRG1 transcript, are part of a regulatory cascade that can cause gene repression.