Skip to main content

Multiscale modelling of fibrinogen during blood clotting

PGR-P-748

Key facts

Type of research degree
PhD
Application deadline
Friday 17 April 2020
Project start date
Thursday 1 October 2020
Country eligibility
UK and EU
Funding
Competition funded
Source of funding
Research council
Supervisors
Dr Oliver Harlen
Additional supervisors
Dr Sarah Harris
Schools
School of Mathematics, School of Physics and Astronomy
<h2 class="heading hide-accessible">Summary</h2>

Now that biophysical techniques such as cryo-EM are revealing highly organised supermacromolecular architectures at the length-scale directly above that of single molecules, which was invisible until very recently, there is a need for new computational tools to interpret these experiments.

<h2 class="heading hide-accessible">Full description</h2>

<p>We have developed mesoscale biomolecular modelling software that provides a continuum mechanics description of very large protein complexes, and which uses biophysical experimental information, such as electron microscopy data, as input to the calculations.&nbsp;The model uses the Finite Element algorithm that we have generalised to include thermal fluctuations, known as Fluctuating Finite Element Analysis (FFEA), we are using this program to model the action of molecular motors such as myosin and dynein, and are improving our physical description of biomolecules and their interactions by adding more accurate representations of biomolecular interactions, which we obtain from atomistic calculations.</p> <p>In this project, we will use experimental data on the fibrinogen protein to model protein assembly during blood clotting, and investigate how this is affected by mutations that change the protein-protein interaction interfaces. Atomistic simulations will be used to understand the interactions between tractable protein fragments, and how mutations change these interactions in the diseased state. We will then use these to parameterise coarse-grained FFEA models to investigate the effect on fibrinogen assembly into the fibrous networks required for blood clots to form. Such a multiscale approach is required because the computational cost of a fully atomistic model would be prohibitively computationally expensive.&nbsp;</p>

<h2 class="heading">How to apply</h2>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://eps.leeds.ac.uk/physics-research-degrees/doc/apply">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &ldquo;Multiscale modelling of fibrinogen during blood clotting&rdquo;&nbsp;as well as&nbsp;<a href="https://eps.leeds.ac.uk/physics/staff/4109/dr-sarah-harris" target="_blank">Dr Sarah Harris</a>&nbsp;as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

<h2 class="heading">Funding on offer</h2>

<p><strong>UK/EU</strong>&nbsp;&ndash; Engineering &amp; Physical Sciences Research Council Studentships paying academic fees&nbsp;(&pound;4,600 for Session 2020/21), together with a maintenance grant paid at standard Research Council rates (&pound;15,285 for Session 2020/21) for 3.5 years. UK applicants will be eligible for a full award paying tuition fees and maintenance. European Union applicants will be eligible for an award paying tuition fees only, except in exceptional circumstances, or where residency has been established for more than 3 years prior to the start of the course. Funding is awarded on a competitive basis.</p>

<h2 class="heading">Contact details</h2>

<p>For further information please contact Doctoral College Admissions,<br /> e:&nbsp;<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a>, t: +44 (0)113 343 5057.</p>


<h3 class="heading heading--sm">Linked funding opportunities</h3>