(MRC DTP) RNA granules: physiological and pathological roles in neurons

RNA granules play key roles controlling mRNA fate in cells. For instance, in neuronal cells these granules are critical in the delivery of mRNAs to axons and dendrites. RNA binding proteins control most aspects of the fate of an mRNA and specific RNA binding proteins, including TDP-43 and hnRNPA1, are critical components of neurodegenerative disorders- such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). Indeed, the aggregation of these RNA binding proteins into inclusions in neurons is a diagnostic feature of these neurodegenerative diseases. This project aims to study the role of mRNA in such processes, as this is currently not well understood. Single molecule FISH will be used in cultured neurons to follow specific mRNAs known to interact with TDP-43 and hnRNPA1. This approach will be combined with studies on how this is altered in response to stress and how the resulting formation of stress granules affects mRNA, TDP-43 and hnRNPA1 function. Genetic approaches will be undertaken to study how disease mutations in TDP-43 and hnRNPA1 impact on these processes. Ultimately, the expected outcome of this PhD is a significantly enhanced understanding of how the interaction of TDP-43 and hnRNPA1 with specific mRNAs alters mRNA fate both in stress and non-stress conditions and how this impacts upon the likely progression of specific neurodegenerative disorders.

https://www.research.manchester.ac.uk/portal/mark.p.ashe.html
https://www.research.manchester.ac.uk/portal/alan.j.whitmarsh.html

Entry Requirements
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.