The importance stress granules as a trigger for neurodegenerative diseases

Lead Research Organisation: University of Sussex
Department Name: Sch of Life Sciences

Abstract

This multidisciplinary research project overlaps with Biophysics and Soft matter physics, polymer materials and condensed matter physics.

Research questions: Abnormal protein assembly is central to a range of neurodegenerative diseases including Alzheimer's and Amyotrophic lateral sclerosis. In these diseases, proteins are deposited in the brain tissue. However, how this protein misfolding is triggered remains unclear. Recent work has inferred that coacervation of proteins and polyanionic molecules such as RNA may play an important role as precursors to protein accumulation. This project aims to address fundamental questions regarding conditions under which proteins may coacervate, polymerise or gel in a reversible or irreversible manner. This work will be conducted in vitro and in vivo to answer key questions related to neurodegeneration disease.

Approach: This PhD project focusses specifically on the normal and abnormal self-assembly of truncated tau protein. Tau is an important neurodegenerative diseases protein, associated with a group of diseases known as the tauopathies, one of which is Alzheimer's disease.
Biophysical measurements will be conducted to monitor the self-assembly, conformational and structural changes to tau under a range of different conditions (pH, temperature, salt) with polyanionic molecules (RNA, heparin etc). Materials properties of the coacervates will be measured in collaboration with Prof Dave Adams (University of Glasgow) (as expert in rheology) and Dr Wei-Feng Xue (University of Kent) (expert in atomic force microscopy). Electron microscopy will be used to follow morphological changes and X-ray fibre diffraction will be used to probe structural information. These studies will be related to cellular studies to monitor the accumulation of stress granules under conditions of stress in a neuroblastoma cell line.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509784/1 01/10/2016 30/09/2021
1805144 Studentship EP/N509784/1 19/09/2016 31/03/2020 KAMILLIA KASBI