Fbxo7/PARK15 is an F-box protein that captures substrates for ubiquitination by SCF-type E3 ligases. We have recently shown that Fbxo7 regulates the autophagy ('self-eating') of mitochondria but the molecular basis for this is not known. To gain some insight into this process, we have conducted high-throughput proteome microarrays and yeast two hybrid screens to identify novel, ubiquitinated substrates of Fbxo7 and discovered several protein components that are potential key regulators of this. The student will perform functional validation of these proteins involved in mitochondrial biology, and can take advantage of model systems in the lab including cultured cell lines, differentiation of stem cells, and mouse models and use biochemistry, cell biology and live cell imaging techniques. Our goal is to determine how Fbxo7-mediated ubiquitination of these proteins regulates mitochondrial turnover and dynamics.
- D. E. Nelson, S. J. Randle and H. Laman. 2013. Beyond ubiquitination: The atypical functions of Fbxo7 and other F-box proteins. Open Biol. 3:130131. http://dx.doi.org/10.1098/rsob.130131.
- V. S. Burchell*, D. E. Nelson*, A. Sanchez-Martinez*, M. Delgado-Camprubi, R. M. Ivatt, J. H. Pogson, S. J. Randle, S. Wray, P. A. Lewis, H. Houlden, A. Y. Abramov, J. Hardy, N. W. Wood, A. J. Whitworth&, H. Laman& and H. Plun-Favreau&. 2013. The Parkinson's disease genes Fbxo7 and parkin interact to mediate mitophagy. Nat Neurosci. 2013 Aug 11. doi: 10.1038/nn.3489. *Equal first authorship. & Equal senior authorship.
- D. E. Nelson and H. Laman. 2011. A competitive binding mechanism between Skp1 and Exportin (CRM1) controls the localisation of a subset of F-box proteins. J Biol Chem. 286(22):19804-15.