Applications are invited for Postdoctoral Fellows in the laboratory of Kathy Gould at Vanderbilt University School of Medicine in Nashville, Tennessee.
--We invite applications from postdoctoral scientists with expertise in structural biology to determine the structure of active CK1 enzymes. CK1 family members have many functions, but the mechanisms regulating these enzymes remain unclear. Determining the structure of active enzyme has not been accomplished for any family member and will provide broadly relevant insight into the CK1 family. The Vanderbilt Center for Structural Biology has state-of-the-art facilities for protein purification, crystallization, characterization, structural analysis and computation.
--We invite applications from postdoctoral scientists with a background in biochemistry and/or yeast genetics who share our interest in mitosis and cytokinesis. We have projects available in all of our research areas.
For all positions, successful applicants will have a proven ability to perform basic research in structural biology, biochemistry and/or yeast genetics, at least one first-author publication, and less than 3 years of relevant postdoctoral experience. To apply for a position, please send a cover letter, CV and the names and contact information for 3 references to Dr. Kathy Gould at firstname.lastname@example.org. General information about being a postdoctoral fellow at Vanderbilt University can be obtained at https://medschool.vanderbilt.edu/postdoc/.
Rotations projects are available in most of our research areas. Here are a few possibilities:
The E3 ubiquitin ligase Dma1 is important for coordinating chromosome segregation and cytokinesis. Dma1 is active during normal mitosis, acting as a brake on Polo-like kinase. Additionally, a Dma1-dependent branch of the mitotic checkpoint delays cytokinesis when the mitotic spindle is disrupted, thus protecting the genome from premature cytokinesis. What cell cycle error triggers Dma1 activation is unknown. Furthermore, while we know that multiple signaling inputs result in phosphorylation or ubiquitination of Dma1, how these modifications impact Dma1 structure and function is unknown. This project will focus on identifying the cellular defects that lead to Dma1-mediated inhibition of cytokinesis and learning how regulatory inputs affect Dma1 structure and function using biochemistry, genetics, and live cell imaging.
The CK1 family of master kinases is involved in many cellular processes and yet our understanding of their regulation is rudimentary. We are focused on two related cytosolic CK1 enzymes that are essential for a cytokinesis checkpoint in fission yeast and are conserved in mammalian cells. To better understand how these enzymes are self-regulated and activated during checkpoint signaling, this project will involve dissecting out the role of multiple phosphorylation sites we have identified in these enzymes. This project will involve biochemistry, genetics and live cell imaging.
In both yeast and mammalian cells, certain members of the CK1 protein kinase family, a master kinase family, contribute to the repair of DNA damage that happens during DNA replication. Without this repair, cells enter mitosis with persistent DNA damage and the integrity of the genome is jeopardized. In this project we will clarify relevant substrates that were previously identified in our lab using a mass spectrometry-based phosphoproteomic screen. Candidate CK1 substrates implicated in DNA damage will be characterized using a combination of biochemistry, genetics and live cell imaging.
The membrane-binding F-BAR protein Cdc15 is essential for contractile ring formation and stability because it helps anchor the division machinery to the plasma membrane. Like other F-BAR proteins, Cdc15 is highly phosphorylated and we have shown that dephosphorylation allows it to oligomerize, bind membranes and scaffold a variety of protein partners. This work established a paradigm of F-BAR regulation by a phosphoregulated oligomeric switch. Surprisingly, at least 4 distinct protein kinases phosphorylate Cdc15 so that it receives input from many signals, raising many questions. Do these kinases have distinct effects on Cdc15? Is Cdc15 a coincidence detector? How is dephosphorylation of Cdc15 coordinated to promote efficient cytokinesis? We are using biochemistry, mass spectrometry, live cell imaging and mathematical modeling to answer these questions. We anticipate that the answers to these questions will continue to inform our understanding of F-BAR proteins involved in diverse biological processes.
Cytokinesis requires the activity of an actin and myosin-based contractile ring structure that constricts to divide one cell into two. The ring must remain anchored to the membrane at the center of the cell during constriction, but how this is achieved is unclear. We are interested in identifying mechanisms that keep the ring in the cell middle and anchored to the membrane. Our approach will be to use a genome-wide genetic screen coupled with live cell imaging to identify new players in this process.