About the Project
The critical balance between the synthesis, maintenance and turnover of all proteins in a cell is a central requirement for life. Following their synthesis and assembly, proteins are frequently subjected to a variety of potentially harmful influences that may result in partial unfolding events that can ultimately result in misfolded or aggregated forms. The accumulation of these damaged proteins can be toxic for the cell. Indeed, disruption to protein homeostasis is a central feature of many cancers, autoimmune diseases and neurodegenerative disorders and the accumulation of damaged proteins is one of the key factors underlying cellular aging processes.
The Asgard superfamily of archaea has been identified as the closest relatives of eukaryotic organisms discovered to date. These intriguing microbes appear to express membrane-associated complexes that could be indicative of vesicular trafficking systems that appear consistent with the evolutionary development of lysosomal protein degradation systems. Furthermore, all archaeal species also possess unequivocal homologues of the ubiquitin-proteasome degradation apparatus. The purpose of this project will be to structurally and biochemically interrogate archaeal homologues of components involved in the key protein homeostasis pathways; the lysosomal and ubiquitin-proteasome degradation systems. A major focus of this project will be to reconstitute thermally stable archaeal homologues of the proteins and complexes that underlie these processes. The project will involve a variety of structural, biochemical and biophysical approaches to further our understanding of these mechanisms. You will learn a variety of experimental techniques including protein expression, the measurement of protein-protein and protein-membrane interactions and perform structural analyses using approaches including protein crystallisation, NMR, electron microscopy and atomic force microscopy. By improving our understanding of the functioning and evolution of these fundamental biological pathways we will glean new insights into the homologous protein homeostasis systems in the eukaryotes and thereby learn more about the evolutionary emergence of complex life. For further reading see Hennel James et al., 2017, Nature Communications 8: 1120; Anjum et al., 2015, Nature Communications 6: 8163; Tarrason Risa et al., 2020, Science (in Press - online as BioRXiv https://doi.org/10.1101/774273).
For informal enquiries and further discussion of the project please contact Dr Nick Robinson, Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University.
Applications are made by completing an application for a PhD in Biomedical and Life Sciences (for October 2020) through our online application system.
Closing date: midnight 2nd August 2020. Interviews will be held in August 21st 2020.
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