A multi-scale multi-modal analysis of Stau1 protein in stress granule formation and disassembly
Supervisors
Laura Spagnolo, School of Molecular Biosciences, University of Glasgow
Richard Burchmore, Infection and Immunity, University of Glasgow
Case Partner - ConnectomX
Summary
Stress granules (SGs) are cytoplasmic assemblies of mRNA and proteins that form from mRNAs stalled in translation initiation in response to stress. SGs participate in various biological functions and are involved in the pathophysiology of neurodegenerative diseases, particularly amyotrophic lateral sclerosis, frontotemporal dementias and Alzheimer disease. Stau1 is an RNA-binding protein central to several RNA metabolism pathways, which is abundant under multiple stressors and localizes to SGs.
Stau1 knockdown facilitates stress granule formation. Conversely, transient transfection of Stau1 impairs stress granule formation upon stress or pharmacological initiation arrest. Stau1 is proposed to be involved in recovery from stress by facilitating stress granule dissolution.
Within the proposed PhD project and in collaboration with ConnectomX, we now plan to integrate emerging volume electron microscopy (vEM) tools and proteomics to unravel the role of Stau1 in SGs formation and disassembly, adding cellular and tissue-specific context to our current BBSRC-funded molecular analysis.
This project will benefit from state-of-the-art facilities and expertise at the University of Glasgow, Research Complex at Harwell and ConnectomX. The student will be trained in cutting edge technology for the study of macromolecular interactions and imaging in RNA metabolism.