EPSRC DTP PhD studentship: Developing novel optical and microfluidic tools to understand protein transporter function and kinetics Ref: 2397

About the award

This project is one of a number which are funded by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership to commence in September 2017. This project is part of a competition for funding. Usually the project which receives the best applicant will be awarded the funding. The studentships will provide funding for a stipend which, is currently £14,296 per annum for 2016-2017, 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 56 projects advertised we expect that up to 20 posts will be filled.

Supervisors:
Main supervisor: Dr Stefano Pagilara (University of Exeter) and Dr. Peter Petrov (University of Exeter)
Co Supervisor: Prof Thomas Richards (University of Exeter)

Location:   University of Exeter, Streatham Campus, Exeter, Devon
                 University of Exeter, Penryn Campus, Cornwall

Project Description:

The plasma membrane of biological cells acts as a barrier but also hosts a number of essential functions ensuring the viability of the cell. One of its main functions is the transport of various compounds across the membrane, e.g. uptake molecules essential for cell survival such as sugars, amino acids and ions and externalisation of molecules such as metabolic products and drugs. Transmembrane transport is usually carried out by special classes of transmembrane proteins, and it is paramount to understand how cells regulate the exchange of molecules in response to changes in the environment. 

This project will develop a novel approach based on model lipid bilayers, microfluidics and microscopy to characterise transport across membrane protein pores and understand the physical mechanisms underlying substrate uptake in living systems. Dr Pagliara’s team recently used giant unilamellar vesicles (GUVs) and microfluidics to investigate molecular uptake through the outer membrane protein F, a transporter shown to play a role in bacterial antibiotic resistance (Cama et al. 2014, Lab Chip 14:2303; Cama et al. 2015, J Am Chem Soc 137:13836). Dr Petrov’s team have a strong track record in investigating elasticity of cell and model membranes (including GUVs) and the role of the membrane physical properties in biological function. Prof Richards’ team has optmised a protocol for purifying and tagging protein transporters to be reconstituted in GUVs. Building on this expertise, the student will obtain GUVs from lipids extracted from different microbial populations and reconstitute fluorescently labelled protein transporters in them. By engineering the geometry of bespoke microfluidic devices, the student will be able to trap GUVs embedded with transporters, deliver putative transported substrates and quantify substrate uptake and the number of reconstituted transporters via fluorescence microscopy. Quantitative image analysis and theoretical modeling (Pagliara et al. 2014, Phys Rev Lett, 113:048102; Locatelli et al. 2016, Phys Rev Lett, 117:038001) will allow determining substrate uptake kinetics, in terms of affinity, half-saturation constant and uptake rate, with single GUV resolution and comparing the different kinetics obtained for different combinations of protein transporters and GUVs. The effect of the reconstituted transporters on the mechanical properties of the membrane will be investigated using fluctuation spectroscopy and micropipette aspiration, techniques available in Petrov’s laboratory.

This project will help clarifying important biophysical questions related to the mechanisms of transmembrane transport in cells and could suggest novel approaches to designing antimicrobial drugs. 
 
Entry requirements:

Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK.   Applicants with a Lower Second Class degree will be considered if they also have Master’s degree.  Applicants with a minimum of Upper Second Class degree and significant relevant non-academic experience are encouraged to apply.  All applicants would need to meet our English language requirements by the start of the  project (http://www.exeter.ac.uk/postgraduate/apply/english/).  

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

Applicants who are classed as International for tuition fee purposes are not eligible for funding.

Summary

Application deadline:11th January 2017
Number of awards:1
Value:3.5 year studentship: UK/EU tuition fees and an annual maintenance allowance at current Research Council rate. Current rate of £14,296 per year
Duration of award:per year
Contact: Doctoral CollegeDoctoral.College@exeter.ac.uk

How to apply

Click here to apply

Please be aware you will be asked 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 on 11 January 2017.  Interviews will be held at the University of Exeter between 13 February and 17 February 2017.

If you have any general enquiries about the application process please email Doctoral.College@exeter.ac.uk
or phone +44 (0)1392 722311.  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.