Molecular characterisation, modelling and prediction of organelle membrane dynamics in health and disease - Biosciences - PhD (Self-Funded) Ref: 3201
About the Research Project
Primary Supervisor: Prof Michael Schrader, University of Exeter
Prof. Peter Winlove, Department of Physics, College of Engineering, Mathematics and Physical Sciences, University of Exeter
Dr. Peter Petrov Department of Physics, College of Engineering, Mathematics and Physical Sciences, University of Exeter
Dr. David Richards (LSI/Centre for Biomedical Modelling and Analysis, University of Exeter)
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 2015, J Inherit Metab Dis 38:681).
Our work has revealed that peroxisomes are extremely dynamic and can form from pre-existing organelles by membrane growth and division, a model which is now generally accepted (Schrader 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 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 cholesterol distribution (Chu 2015, Cell 161:291; Thazar 2015, PNAS 112:4158), lipid transfer and synthesis (Costello 2017, JCB 216:331). Overall, this highlights the importance of peroxisome dynamics for cell viability and human health. Despite their importance for cell physiology, peroxisomal membrane dynamics are not well understood and a biophysical model is missing.
This multi-disciplinary project will therefore combine molecular cell biology approaches (M. Schrader, Bioscience) with membrane biophysics approaches (P. Winlove/P. Petrov, Physics) and expertise in mathematic modelling of organelle dynamics (D. Richards, CBMA). We will use molecular cell biology, protein biochemistry and high-resolution microscopy to generate ultrastructural, imaging, and live cell data on molecular components of the growth and division machinery (e.g. Pex11p, a key factor of peroxisome dynamics) (Delille 2010, JCS 123:2750; Williams 2015 PNAS 112:6377) and their impact on organelle dynamics.
Novel and existing data will be combined with approaches to determine protein/lipid interactions and biophysical forces that modulate membrane dynamics with the aim of ultimately generating a mathematical biophysical model on peroxisome/organelle membrane dynamics. With this multi-disciplinary approach we aim to unravel new basic biological and biophysical principles, to understand the mechanisms of peroxisomal membrane remodelling in health and disease, and to be able to predict membrane alterations that can be verified in established cell models and patient cells.
For more information about the project and informal enquiries, please contact the primary supervisor, Prof Michael Schrader
Things to consider:
Information about current fees : https://www.exeter.ac.uk/pg-research/money/fees/
Information about possible funding sources: http://www.exeter.ac.uk/pg-research/money/alternativefunding/
Information about Doctoral Loans: http://www.exeter.ac.uk/pgresearch/money/phdfunding/postgraduatedoctoralloans/
You should have or expect to achieve at least a 2:1 Honours degree from a UK university, or equivalent, in Biological Sciences, Biochemistry or Biophysics, and expect to achieve at least a merit (or equivalent) in a taught Master’s degree. Experience in molecular cell biology, protein biochemistry, fluorescence-based microscopy, mammalian cell culture, or membrane biophysics is desirable.
If English is not your first language you will need to meet the English language requirements and provide proof of proficiency. Click here for more information and a list of acceptable alternative tests.
How to apply
You will be asked to submit some personal details and upload a full CV, covering letter and two academic references. Your covering letter should outline your academic interests, prior research experience and reasons for wishing to undertake this project.
You may also be asked to upload verified transcripts of your most academic qualification.
Please quote reference 3201 on your application and in any correspondence about this project
|Application deadline:||7th January 2019|
|Value:||This project is self-funded|
|Duration of award:||Not applicable|
|Contact: PGR Enquiriesemail@example.com|