Biophysics of Peroxisome Division- Physics and Astronomy- EPSRC DTP funded PhD Studentship Ref: 2915

About the award

This project is one of a number funded by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership to commence in September 2018. This project is in direct competition with others for funding; the projects which receive the best applicants will be awarded the funding.

The studentships will provide funding for a stipend which is currently £14,553 per annum for 2017-2018. It will provide research costs and UK/EU tuition fees at Research Council UK rates for 42 months (3.5 years) for full-time students, pro rata for part-time students.

Please note that of the total number of projects within the competition, up to 15 studentships will be filled.

Supervisors
Dr Peter G. Petrov

Prof. C. Peter Winlove

Location 
Streatham Campus,Exeter.

Project Description
Organelles are small membrane-bound compartments within cells that play important roles in the function and maintenance of all cell types. Our work has for some time focused on the peroxisome which plays vital roles in lipid metabolism and the elimination of oxidative stress. Peroxisomes are essential for human health and development and defects in their formation and function have been linked to neurodegeneration, liver disease and age-related disorders. These organelles are highly dynamic and can be formed by membrane growth and division. This requires the formation of tubular membrane extensions which subsequently constrict and divide into several new peroxisomes. We have identified key proteins in this process, some of which have recently been linked to disorders affecting peroxisome multiplication. Of particular interest is Pex11β, a peroxisomal membrane protein with remarkable lipid modifying properties, which induces the formation of long membrane tubules. How these proteins remodel the peroxisomal membrane is currently unknown and the role of the membrane biophysical properties in such processes is far from clear. 

This project will focus on biophysical studies on the interaction between the protein Pex11 and lipid membranes to reveal novel and important insights into the fundamental process of peroxisome multiplication. This is a multidisciplinary project combining the biological expertise of Michael Schrader’s laboratory (Biosciences) on organelle biology and the membrane biophysics approaches established by Peter Petrov and Peter Winlove in Physics, and Catalin Chimerel in LSI. The interactions between Pex11 peptides and membranes will be studied by:

1. Langmuir trough measurements. This technique allows the study of the interactions between Pex11 peptides and a monolayer of peroxisomal lipids spread at an air-water interface (a model of the peroxisomal membrane). The composition of the monolayer can be fully controlled which will allow the main lipid species primarily responsible for the Pex11-membrane interactions to be identified and resulting changes in membrane mesoscopic organisation and physical properties characterised. 

2. Giant vesicle measurements and planar lipid bilayers measurements. Certain Pex11 peptides are known to induce the formation of tubules in peroxisomal membranes. To investigate this process, we will use two model membrane systems, giant vesicles and planar lipid membranes. These experiments will reveal the impact of the protein on the preferred curvature of the membrane. In complementary experiments, we will investigate the spatial arrangement of the PEX11 peptide and cruster formation in the membrane using state of art CryoEM facilities at Christiane Berger-Schaffitzel’s laboratory in Bristol.  

3. Pex11 peptide interaction with the plasma membrane. We have developed techniques based on the analysis of thermal membrane fluctuations of erythrocytes to assess the effects of the protein-membrane interactions on the membrane curvature and mechanical properties, and fluorescent probe methods of characterising its electrical properties. The erythrocyte membrane is a more realistic model than monolayers and vesicles and we shall investigate the effects of interactions with the tubule-forming peptides derived from Pex11. This will clarify the stages of interaction between Pex11 and the membrane, its effect on membrane curvature (which is directly related to tubule formation) and changes in the elastic and electrical properties of the plasma membrane. 

Together, these investigations will provide vital steps in building a biophysical model of tubule formation from peroxisomes and enable the validation of novel methodologies that will be used in future research.

 

Entry Requirements

You should have or expect to achieve at least a 2:1 Honours degree, or equivalent, in Physics, Physical Chemistry or Biology. Experience in membrane research is desirable but not essential as full training will be provided.

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.

The majority of the studentships are available for applicants who are ordinarily resident in the UK and are classed as UK/EU for tuition fee purposes.  If you have not resided in the UK for at least 3 years prior to the start of the studentship, you are not eligible for a maintenance allowance so you would need an alternative source of funding for living costs. To be eligible for fees-only funding you must be ordinarily resident in a member state of the EU.  For information on EPSRC residency criteria click here.

Applicants who are classed as International for tuition fee purposes are NOT eligible for funding. International students interested in studying at the University of Exeter should search our funding database for alternative options.

Summary

Application deadline:10th January 2018
Value:3.5 year studentship: UK/EU tuition fees and an annual maintenance allowance at current Research Council rate. Current rate of £14,553 per year.
Duration of award:per year
Contact: Doctoral Collegepgrenquiries@exeter.ac.uk

How to apply

You will be required to upload the following documents:
•       CV
•       Letter of application outlining your academic interests, prior research experience and reasons for wishing to
        undertake the project.
•       Transcript(s) giving full details of subjects studied and grades/marks obtained.  This should be an interim
        transcript if you are still studying.
•       If you are not a national of a majority English-speaking country you will need to submit evidence of your current
        proficiency in English.  For further details of the University’s English language requirements please see
        http://www.exeter.ac.uk/postgraduate/apply/english/.

The closing date for applications is midnight (GMT) on Wednesday 10 January 2018.  Interviews will be held at the University of Exeter in late February 2018.

If you have any general enquiries about the application process please email: pgrenquiries@exeter.ac.uk.
Project-specific queries should be directed to the supervisor.

During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates.  These are not limited to, but may include disclosures to:

• the selection panel and/or management board or equivalent of the relevant programme, which is likely to include staff from one or more other HEIs;
• administrative staff at one or more other HEIs participating in the relevant programme.

Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.