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Our lab is interested in the systems biology and evolution of epigenetic switches (bistability) and clocks (oscillators) in gene regulatory networks. We use experiment and theory, biology and physics, systems and synthetic biology to study the cell cycle, metabolic rhythms, and circadian clocks. How do oscillators with different frequencies co-exist in the same cell? Are there mechanisms and regulatory principles that ensure functional harmony between oscillators?

Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi

Spizellomyces_punctatus_2000pixelsAlthough cell cycle control is an ancient, conserved, and essential process, some core animal and fungal cell cycle regulators share no more sequence identity than non-homologous proteins. Edgar Medina used a phylogenomic approach to show that evolution along the fungal lineage was punctuated by the early acquisition and entrainment of SBF transcription factor through horizontal gene transfer. Cell cycle evolution in the fungal ancestor then proceeded through a hybrid network containing both SBF and its ancestral animal counterpart E2F, which is still maintained in many basal fungi (e.g. Spizellomyces punctatus, shown in picture). We hypothesized that a virally-derived SBF may have initially hijacked cell cycle control by activating transcription via the cis-regulatory elements targeted by the ancestral cell cycle regulator E2F, much like extant viral oncogenes. Consistent with this hypothesis, our data show that SBF can regulate promoters with E2F binding sites in budding yeast. This was a fun and fruitful collaboration with the Skotheim and Gordan labs.  You can read more about this research (“Hijacked cell division helped fuel rise of Fungi” by Robin A. Smith) at Duke Today.

Medina EM, Turner JJ, Gordan R, Skotheim JM, Buchler NE. Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi. eLife 5:e09492 (2016)
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