Control of Cytoplasmic Protein Aggregation by the Cell-Autonomous Immune System (PhD only)

Individual cells are capable of defending themselves against microbial and viral infection in the absence of direct co-ordination by the professional immune system. The effector proteins of this ‘cell-autonomous’ immunity provide a crucial last line of defence against infection against infection and are constitutively expressed in numerous cell types. Our lab investigates how this form of immunity can be brought to bear on self-propagating protein species that are implicated in neurodegeneration. We recently demonstrated that aggregates of tau, a protein which becomes aggregated in several progressive forms of neurodegeneration including Alzheimer’s disease, can be inactivated in this way (McEwan et al 2017 PMID: 28049840).
Ongoing work in our lab has identified further cellular conditions where aggregation of tau is substantially reduced and genes of the cell-autonomous immune system are implicated. The aim of the project is to characterise the pathways involved in the suppression of protein aggregation. Given that there is currently little understanding of how cellular mechanisms can limit templated protein aggregation, the results may provide an important understanding of cellular pathways that limit disease progression. We will use a range of cell-based and molecular techniques to characterise the relevant genes and pathways involved. Students with an interest in infection and immunity as well as neurodegeneration are encouraged to apply. Knowledge of molecular biology and biochemical techniques is essential.