Evolution of new Rb and E2F interactions in jawed vertebrates

screen-shot-2017-05-09-at-12-53-45-pmThe retinoblastoma protein (Rb) was the first cloned tumor suppressor gene, and its study established the paradigm for how loss of cell cycle control contributes to tumorigenesis.  One long-standing question is why is Rb a more potent tumor suppressor than its close Rb-like homologs p107 and p130. Here, we addressed this question by identifying differences in Rb and p107 structure and the source of their preferences in binding different E2F transcription factor family members. We combined these insights with comparative genomics to show that Rb evolved structural features that confer a unique ability to bind those E2Fs that most potently activate cell division. This protein-protein evolution occurred at the base of jawed vertebrates after their divergence from Agnatha (jawless fish). This was a fun cell cycle collaboration between the Rubin (biochemists) and Buchler labs (genomicists).

Liban TJ, Medina EM, Tripathi S, Sengupta S, Henry RW, Buchler NE, Rubin SM. Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family. Proc. Natl. Acad. Sci. USA 114: 4942 (2017)

Mitchell Lee graduates with Distinction

Screen Shot 2014-06-30 at 08.59.18Mitch worked on synthetic biology as an independent research project for several years. The goal was to design a toggle switch that used a basic leucine zipper (C/EBPa) and a dominant-negative (3HF). His results were submitted as a honor’s thesis and he graduated with distinction in Biology. Congratulations!

Lee M (2017). Designing a genetic toggle switch for E. coli that uses sequestration of a eukaryotic repressor as a mechanism for ultrasensitivity.

Selcan and Tony defend their PhDs

selcantony-defense2017Tony Burnetti and Selcan Aydin defended their dissertations on back-to-back days! Double congrats to these new PhDs posing with Selcan’s magnum of champagne.

Tony defended his dissertation on the “Coupling of the Yeast Metabolic Cycle and the Cell Division Cycle in Populations and Single Cells“. Tony’s committee was Paul Magwene (Biology), Amy Schmid (Biology), Philip Benfey (Biology), and Nicolas Buchler (Biology & Physics). Tony is now a University Program in Genetics & Genomics PhD.

Selcan defended her dissertation on “Understanding the Effects of Genetic Variation on Osmo-adaptation Dynamics Across Saccharomyces cerevisiae using Bulk Segregant Analysis and Whole Genome Sequencing“. Selcan’s committee consisted of Paul Magwene (Biology), Tom Mitchell-Olds (Biology), John Willis (Biology), Amy Schmid (Biology), Danny Lew (Pharmacology & Cancer Biology), and Nicolas Buchler (Biology & Physics).  Selcan is now a Biology PhD.