PhD Studentship: Molecular Characterisation, Modelling and Prediction of Organelle Membrane Dynamics in Health and Disease (BBSRC Funded)

University of Exeter - College of Life and Environmental Sciences

The South West Biosciences Doctoral Training Partnership (SWBio DTP) is a BBSRC-funded PhD training programme in the biosciences, delivered by a consortium comprising the Universities of Bristol (lead), Bath, Cardiff, Exeter, and Rothamsted Research. Together, these institutions present a distinctive cadre of bioscience research staff and students with established international, national and regional networks and widely recognised research excellence. The partnership has a strong track record in advancing knowledge through high quality research and teaching in partnership with industry and government.

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP).  Up to 4 fully-funded studentships are being offered to start in September 2018 at the University of Exeter.

Academic Supervisors:

Main supervisor: Prof Michael Schrader

Co-supervisor: Prof Christiane Berger-Schaffitzel

Co-supervisor: Dr David Richards

Co-supervisor: Prof Peter Winlove

Co-supervisor: Dr Peter Petrove

Collaborator: Prof Peter Ashwin

Collaborator: Prof Ana Garcia

Location:

University of Exeter, Streatham Campus, Exeter

Project description:

Research on organelle membrane dynamics represents an exciting new field in modern cell biology and biomedical sciences because of its close relation to organelle functionality and its impact on developmental and physiological processes. Peroxisomes represent ideal model organelles as they have only one limiting membrane, can be easily labelled and are biochemically accessible. Vital, protective roles of peroxisomes in lipid metabolism, signalling, the combat of oxidative stress and ageing have emerged recently (Islinger & Schrader 2011, Curr Biol. 21:R800; Schrader et al. 2015, J Inherit Metab Dis 38:681). Our work has revealed that peroxisomes are extremely dynamic and can be formed from preexisting organelles by membrane growth and division, a model which is now generally accepted (Schrader et al. 2012, BBA 1822:1343).

This requires remodelling of the peroxisomal membrane, the formation of tubular membrane extensions which subsequently constrict and divide into several new peroxisomes. Defects in membrane dynamics and multiplication of peroxisomes have been linked to novel disorders involving neurodegeneration, loss of sight and deafness (Delmaghani et al. 2015, Cell 163:894). Very recently, it was discovered that peroxisome interaction with other organelles, which depends on peroxisome number and membrane protrusion, is crucial for the distribution of cholesterol within the cell, as well as for lipid breakdown/synthesis and protein/lipid exchange (Chu et al. 2015, Cell 161:291; Thazar et al. 2015, PNAS 112:4158; Costello et al. 2017, J Cell Biol 216:331). Overall, this highlights the importance of peroxisome dynamics for cell viability and human health. Despite their importance for cell physiology and homeostasis, the membrane dynamics of peroxisomes are not well understood and a biophysical model is missing.

This multi-disciplinary project combines cutting-edge biological, biophysical and modelling approaches to understand the mechanisms, principles and functions of organelle membrane dynamics in health and disease. This work will help to predict alterations in membrane dynamics and to propose treatments for patients with defects in organelle dynamics and related dysfunctions.

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Type / Role:

PhD

Location(s):

South West England