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Molecular characterisation, modelling and prediction of organelle membrane dynamics in health and disease PhD in Biosciences Studentship (BBSRC SWBio DTP funded)


College of Life and Environmental Sciences

About the Project

The SWBio DTP is one of the 12 Doctoral Training Partnerships funded by the BBSRC to provide PhD training in areas of their strategic relevance. The SWBio DTP is 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 aim of this DTP is to produce highly motivated and excellently trained postgraduates in the BBSRC priority areas of Agriculture & Food Security (AFS) and World-Class Underpinning Bioscience (WCUB). These are growth areas of the biosciences and for which there will be considerable future demand.

The award:

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP).

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 pre-existing 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; Passmore 2020, BBA 1867:118709). Recently, it was discovered that peroxisome interaction with other organelles, which depends on peroxisome number and membrane protrusion, is crucial for cholesterol distribution, lipid transfer and synthesis (Costello 2017, JCB 216:331; Schrader 2020, JInherit Metab Dis 43:71).

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 requires development. This multi-disciplinary project combines cutting-edge biological, biophysical and modelling 5 / 569 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.

Funding Notes

BBSRC SWBio DTP funded CASE studentship available for September 2021 entry. The studentship will provide funding of fees and a stipend which is currently £15,285 per annum for 2020-21, on a full time basis.

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