Network Control of Rhythmic Behavior: From Cell Division to Infectious Disease


Monday, December 4, 2023 - 3:30pm to 4:30pm


ESB 1001


Professor Steve Haase

The Haase Lab is broadly interested in the systems-level mechanisms controlling rhythmic behavior in a variety of organisms. We focus on understanding how cells regulate periodic events during the cell-division cycle in budding yeasts and the interaction between parasite developmental cycles and host circadian cycles during malaria infections. The unifying theme in these seemingly disparate systems is that rhythmicity appears to result from large periodic programs of phase-specific gene expression that control the ordered expression of regulatory genes driving landmark events. A Gene Regulatory Network (with similarities to circadian clocks) serves as the central oscillating mechanism driving cell-cycle regulated gene expression and other cell-cycle events in S. cerevisiae. Recent unpublished work revealed how relatively small perturbations to the GRN can drive endocycles in which both DNA and spindle poles are replicated without intervening mitoses. These endocycles produce vegetatively growing polyploid cells that eventually resolve into cells of lower ploidy, including aneuploid populations. These phenotypes are features of both tumor cells and fungal pathogens during infection. During malaria infection, we have uncovered evidence that the 48hr intra-erythrocytic cycle is controlled by a parasite-autonomous clock that regulates the periodic expression of most of the genome. In a study of human subjects with an active malaria infection, we demonstrate the 48hr parasite-intrinsic clock is coupled to the 24hr host circadian clock. Integrated genetic, genomic, computational, and mathematical modeling approaches in these two systems will be discussed.

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