Cellular regulation through signaling cascades that culminate in reversible post-translational modification (PTM) of effector proteins are among the most studied areas of basic cell biology. The best understood PTM is phosphorylation, and the enzymes that catalyse it, kinases and phosphatases, are frequently identified as potential therapeutic targets. Palmitoylation, the reversible addition of a long chain fatty acid to cysteine residues, is a much less studied PTM which can control protein trafficking, stability, signaling, and complex formation. The development of mass spectrometry techniques to study protein palmitoylation has radically changed our understanding of the diversity of proteins that are affected by this PTM. These experiments have made clear that, like phosphorylation, palmitoylation is a regulatory tool that has an impact on a wide range of essential eukaryotic processes, with more than 10% of proteins in a given cell type being palmitoylated. However we currently know little about the enzymes that catalyse the removal and addition of palmitoyl groups. This project will use an array of biochemical, mass spectroscopy and genetic approaches to study palmitoyl transferases in Apicomplexan parasites, which are ideal models for study because they have a reduced repertoire of palmitoyl transferases relative to other eukaryotic cells. The project will use affinity purification and mass spectrometry to identify protein-protein complexes involving palmitoyl transferases, and develop new proteomic techniques to systematically identify palmitoylation sites for the first time. The student will learn a comprehensive range of cell biological techniques, and be involved in the development of new proteomic mass spectrometry methods.
- Roth, A.F., et al. (2006) Global analysis of protein palmitoylation in yeast. Cell 125, 1003-1013.
- Martin, B.R. and Cravatt, B.F. (2009) Large-scale profiling of protein palmitoylation in mammalian cells. Nat Methods 6, 135-138.
- Jone, M.L. et al. (2012) Analysis of Protein Palmitoylation Reveals a Pervasive Role in Plasmodium Development and Pathogenesis. Cell Host & Microbe 12(2), 246–258.