Multiple scale modelling of skeletal muscle bioenergetics with applications to cystic fibrosis. Mathematics, PhD (GW4 BioMed MRC DTP) Ref: 3236

About the award

Supervisors

Lead supervisor: 
Dr Kyle Wedgwood, Department of Mathematics, Living Systems Institute, University of Exeter

Additional supervisors: 
Dr James Betts, University of Bath
Professor Craig Williams, Department of Sport and Health Sciences, University of Exeter 

Project Details

Despite significant advances in knowledge of muscle and exercise physiology, it remains difficult to make quantifiable predictions about aerobic fitness, even in healthy groups. This is due, in part, to the lack of tools to integrate information about these systems from different sources and across different spatial and temporal scales. Mathematical modelling has the potential to bridge these scales in a quantifiable, verifiable and predictive manner. This project will develop and analyse a mechanistic mathematical model of skeletal muscle bioenergetics, describing adenosine triphopshate (ATP) turnover during muscle contraction and metabolism.   

Once formed, the model will be used to estimate whole-body energetic parameters via fitting to magnetic resonance spectroscopy data collected during aerobic exercise. These parameters will then be used to provide a quantitative link between calorimetry measurements of oxygen uptake during exercise to rates of aerobic and anaerobic metabolism at the tissue level. In so doing, the model will bridge scales between single cell, tissue and whole-body dynamics. Finally, the model will be used to explore aberrations in muscle metabolism and contractility associated with cystic fibrosis. Importantly, the model will investigate how exercise therapy can mitigate these aberrations.   

This interdisciplinary project leverages large quantities of unique physiological data obtained at the Universities of Exeter and Bath, and our international partners (UNAM-National Autonomous University of Mexico & University of Toronto). These will be used to support state-of-the-art techniques in parameter optimisation and uncertainty quantification to capture variation in parameters across populations. The project thus involves significant amounts of data analysis, in conjunction with the construction of multiscale mathematical models. The fields of uncertainty quantification and multiscale modelling are at the forefront of mathematical biology research, and this project will therefore advance both understanding of muscle physiology and applied mathematics.   

Given the importance in measuring and improving aerobic fitness in people with cystic fibrosis, there are clear avenues for translating the proposed research. In particular, the student will have direct access to patient data collected throughout the project via Williams' funded 4 year Strategic Research Centre award by the Cystic Fibrosis Trust UK. These data and the model will be combined to predict how changes to aerobic fitness may be realised during therapy. This project will build on previous research by the supervisory team (Wellcome Trust ISSF funding 2015-6) and direct future planned projects will be a long-term aim of developing model-based decision support software for clinicians treating people with cystic fibrosis.


Funding
This studentship is funded through GW4 BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£14,777 for 2018/19, updated each year) for 3.5 years.

For further information relating to the funding please see the main MRC GW4 BioMed website

This project is in competition with 69 other projects; up to 18 studentships will be available


Eligibility and Residency Requirements
To be eligible for a full award (fees and stipend) from a Research Council, a UK or EU student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship.

An EU student who has not been resident in the UK for at least 3 years prior to the start of the studentship is generally eligible for a fees-only award from the Research Council: to be eligible for a fees-only award, a student must be ordinarily resident in a member state of the EU; in the same way as UK students must be ordinarily resident in the UK.

For our regular recruiting round, the Doctoral Training Partnership has additional funding from the partner universities to support a limited number of EU students who do not meet the UK residency requirements, so long as they meet the criteria for a fees-only award: these studentship will therefore be fully funded (fees and stipend).

For full details on eligibility, please refer to the MRC GW4 BioMed website

Students with 'International' status are unfortunately not eligible to apply.


Data Protection
If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.

Your personal data will always be processed in accordance with the  General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).

For further information regarding data protection for the Application Process and if you become a student on one of the Programmes please click here


Further Information
For an overview of the MRC GW4 BioMed progamme, please see the website www.gw4biomed.ac.uk

Entry requirements

Academic criteria
In addition to those with traditional biomedical or psychology backgrounds, the DTP welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences, and can fund additional training, including Masters to assist discipline conversion. Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant non-academic experience.

English requirements
If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.5 in any section) by the start of the programme.

How to apply

Applications Open on 24 September and close at 17:00 on Friday 23 November 2018

You will need to complete an application to the GW4 BioMed MRC DTP for an 'offer of funding'

Applying for an 'offer of funding'

Please complete the application form at https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-dtp-student-2019 by 5pm Friday 23 November 2018. 

The Research Theme Panels will complete the shortlisting and inform applicants by 18th December 2018.  If you are shortlisted you will need to:

  • contact your chosen supervisor(s) to arrange an informal meeting (which can be in person, by telephone or by Skype) with the Lead supervisor of the projects in which you are interested by, 14 January 2019.  Please note that interview expenses will not be available for candidates to attend these meetings.
  • Attend a formal interview, with a panel of four academics which will take place in Cardiff toward the end of January. 

For further details of the application process please see the following web page www.gw4biomed.ac.uk/doctoral-students/

You do NOT need to apply to the University of Exeter at this stage - only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Exeter.

Summary

Application deadline:23rd November 2018
Value:Stipend matching UK Research Council National Minimum (£14,777 p.a. for 2018/19, updated each year) plus UK/EU tuition fees
Duration of award:per year
Contact: PGR Enquiries pgrenquiries@exeter.ac.uk