Erin O'Shea, PhD

Professor

Department of Molecular and Cellular Biology, Faculty of Arts and Sciences

Howard Hughes Medical Institute
Professor of Chemistry and Chemical Biology
Director, Center for Systems Biology

Cellular signaling pathways and regulation of gene expression

Studies of how cells are monitoring the environment and the resulting response via regulation of gene expression in simple model organisms. Investigates the evolution of transcription regulation; deciphering the logic of signaling and transcriptional control. Understanding the function and mechanism of oscillation of a three-protein circadian clock.

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Commercial Opportunities

The O’Shea laboratory focuses on systems biology and takes advantage of simple model organisms to gain understanding into complex cellular biological mechanism. The studies being performed are laying the groundwork for future therapeutics and biomedical solutions related to human health. Several fundamental pathways have been studied; firstly a signaling pathway effecting of regulation of gene expression in response to changes in nutrient homeostasis using budding yeast, S. cerevisiae, as a model organism. Specifically critical control components of inositol polyphosphate metabolism have been elucidated; importantly this pathway is evolutionally conserved and has been implicated in human cell grow control and cancer.

Another focus has been the study of transcriptional rhythms and how they are controlled by an endogenous biological clock to allow organisms to schedule processes at appropriate times during the day and night cycle. The study at the laboratory takes advantage of a model system S. elongatus, however the circadian rhythms in gene expression have been identified in many organisms, and most importantly a large body of data supports our understanding that perturbation of their control mechanisms could leads to many health related problems and disease states.

These studies present commercial opportunities in multiple fields, and most importantly fundamental approach of systems biology and computational analysis using simple model organisms presents a unique and powerful tool system for biomedical research and development.

Current Research Interests
  • Investigate the phosphate-responsive signaling pathway in budding yeast as a model for nutrient sensing, signal transduction, and transcription factor regulation.
  • Study regulatory regions of genes to understand how the promoters transform information about transcription factor input into quantitative gene expression output.
  • Study the Cyanobacterial Circadian Clock to understand mechanism of timekeeping and circadian rhythms based on light-dark cycle.
Tools and Assays
  • Systems biology
  • Mathematical model
  • High throughput assays
Research Expertise

The O’Shea laboratory has revealed some of the central mechanisms of the phosphate-responsive signaling pathway using budding yeast, S. cerevisiae, as a model system. They investigate signal transduction and the regulation of transcription factor activity upon changes in nutrient phosphate availability. They have uncovered components critical for regulation of a cyclin-CDK complex, and have elucidated the molecular mechanisms underlying genetic interactions between inositol polyphosphate metabolism and the phosphate-responsive signaling pathway in yeast. They are currently performing a genome-wide screen to identify genes whose products are involved in phosphate sensing. This screen may reveal new connections between phosphate metabolism and other nutrient-sensing and metabolic pathways.

Using systems biology and whole genome high throughput expression analysis, the group has been examining transcription control mechanisms in relationship to chromatin structure, promoter organization and transcription factor input. Using a yeast model system they have been characterizing the role of signal integration and processing in gene regulatory networks. The network model approach can be extended to other systems to study conditionally activated pathways using gene knockouts, RNAi, or chemical inhibitors.

Another focus of the O’Shea laboratory has been illuminating key control elements that govern circadian rhythms in gene expression using cyanobacterium Synechococcus elongatus as a model organism. In addition to elucidation of the mechanism of timekeeping of this simple circadian clock, the O’Shea lab has uncovered a novel mechanism of DNA supercoiling-mediated control of circadian gene expression.