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Researcher
Post-Doc Centriole Duplicaiton Checkpoint in Cell Cycle Full-time
The laboratory of Dr. David Glover in the Division of Biology and Biological Engineering at the California Institute of Technology in Pasadena, CA, is seeking a highly motivated postdoctoral research fellow. The Glover lab recently moved to Caltech from the University of Cambridge and investigates aspects of cell cycle control that relate to the centriole duplication cycle. We have a strong background in using Drosophila as an experimental model and then translating our findings to equivalent processes in mammalian cells to place them into the context of physiology and disease, including different forms of cancer. We first discovered the Plk4 protein kinase plays a master role in regulating centriole duplication (Bettencourt Dias et al (2005) Current Biol. 15: 2199-207; Rodrigues-Martins et al 2007 Science 316: 1046-1-50; Dzhindzhev et al., 2010 Nature 467, 714-718; Dzhindzhev et al., 2014 Curr Biol. S0960-9822(14)01074-4. doi: 10.1016). We showed that over-expression of Plk4 in mice advances the onset of tumour formation that occurs in the absence of the tumour suppressor p53 and also results in hyperproliferation of cells in the pancreas and skin that is enhanced in a p53 null background (Coelho et al., 2015 Open Biol Dec;5(12). pii: 150209. doi: 10.1098).
To identify proteins that signal or respond to the presence of extra centrosomes, we have carried out a genome-wide screen on cell lines representing these mice to identify genes that when deleted or knocked-down permit the proliferation of cells with supernumerary centrosomes as a result of elevated Plk4. As a result, we have identified several new pathways whereby cells respond to supernumerary centrosomes and now wish to understand how these pathways participate in regulating the centriole duplication cycle and signalling the response to supernumerary centrosomes. To this end we use quantitative single-cell and super-resolution imaging methods combined with molecular biology, biochemical, genetic, and proteomic approaches. We anticipate that our study will identify pathways that can be targeted for restoring centriole numbers or cell cycle regulation in tumor cells or for targeting such cells for apoptosis. The postdoctoral fellow will determine the interplay of factors regulating centriole duplication, cilia formation, and cell proliferation; determine the cellular mechanisms for eliminating excessive Plk4; and study the relationship between centriole elongation and cohesion and cell cycle progression.
The applicant must have received, or be scheduled to receive, a Ph.D. in cell biology, biochemistry, molecular biology, or other related fields by the start of the appointment. A strong record of research productivity is required. Expertise in molecular cloning is required and previous experience in one or more of the following techniques/fields is strongly preferred: mammalian cell biology, CRISPR-mediated genome-editing, quantitative live-cell optical imaging, protein purification, proximity-based labelling for quantitative mass spectrometry. How to apply: Interested applicants should email Dr. David Glover (dmglover@caltech.edu) a CV with a description of past research experience and future research interests. Following an initial screening of these application materials, appropriate candidates will be contacted by email for letters of reference.