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Direct characterisation of TRPC channel dynamics triggered by drug-like modulators using high-speed atomic force microscopy

PGR-P-423

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Country eligibility
UK and EU
Funding
Competition funded
Supervisors
Dr Robin Bon and Dr George Heath
Schools
School of Biomedical Sciences, School of Physics and Astronomy
Research groups/institutes
Leeds Institute of Cardiovascular and Metabolic Medicine, Molecular and Nanoscale Physics
<h2 class="heading hide-accessible">Summary</h2>

The rapid expansion in the structural understanding of membrane proteins through recent progress in electron microscopy and X-ray crystallography is leading to an ever greater need for techniques which provide high temporal resolution dynamics. High-Speed Atomic Force Microscopy (HS-AFM) gives unprecedented real-space and real-time visualisation of biological molecules (&lt;1 nm lateral, ~0.1 nm vertical and &gt;100 ms temporal resolution). This offers the unique capability to directly study how protein function can be modulated by various small molecules and stimuli to inform the pursuit of therapeutics. Transient receptor potential canonical (TRPC) 1/4/5 channels are found in many cell types including the nervous and cardiovascular systems, where they form nonselective cationic channels with high calcium permeability. Structural and mechanical knowledge of these channels is rapidly evolving, suggesting TRPC1/4/5 assemblies play crucial roles in human physiology and pathology, and consequently are potential drug targets for renal failure, anxiety, cancer, pain, and cardiac remodeling. Our goal is to study the dynamic structural changes in TRPC1/4/5 assemblies reconstituted into near-native membranes as a function of modulators by high speed AFM. The mechanisms we aim to uncover will not only be applicable to TRPC but also to all other TRP and heteromeric ion channels for which structural information is scarce and will therefore have important implications for general channel physiology and pharmacology. This highly interdisciplinary research will be performed in the School of Physics and Astronomy at the University of Leeds in collaboration with researchers in Leeds Institute of Cardiovascular and Metabolic Medicine.

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

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="http://www.leeds.ac.uk/rsa/prospective_students/apply/I_want_to_apply.html">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 &lsquo;Direct characterisation of TRPC channel dynamics triggered by drug-like modulators using high-speed atomic force microscopy&rsquo; as well as&nbsp;<a href="https://eps.leeds.ac.uk/physics/staff/6132/dr-george-heath">Dr George Heath</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. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<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. Some schools and faculties have a higher requirement.

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

<p><strong>Funding Eligibility - UK/EU&nbsp;</strong>&ndash;&nbsp;Leeds Doctoral Scholarship Award paying Academic Fees and Maintenance matching EPSRC rate of &pound;15,009 per year for 3 years, School of Physics &amp; Astronomy Scholarship award paying Academic Fees and Maintenance matching EPSRC rate of &pound;15,009 per year for 3 years.&nbsp; Alumni Bursary is available to previous University of Leeds graduates offering 10% discount on Academic Fees. Please contact the supervisor for advice on applying.</p> <p>&nbsp;</p> <p><strong>Funding Eligibility - International Students</strong>&nbsp;&ndash;&nbsp;China Scholarship Council-University of Leeds Scholarship Award paying Academic Fees for 3 years,&nbsp;School of Physics &amp; Astronomy Fee Only Scholarship award paying Academic Fees for 3 years, Commonwealth Scholarship and Commonwealth Split Site Scholarships.&nbsp; Alumni Bursary is available to previous University of Leeds graduates offering 10% discount on Academic Fees. Please contact the supervisor for advice on applying.</p> <p>&nbsp;</p> <p><strong>Self-funded students</strong>are also very welcome to apply.</p>

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

<p>For further information on the project do not hesitate to contact any of the project supervisors by email (e.g. George Heath at&nbsp;<a href="mailto:p.g.adams@leeds.ac.uk">g.r.heath@leeds.ac.uk</a>). We are always happy to discuss scientific questions with pro-active candidates. For details on how to apply and admin arrangements, please contact Doctoral College Admissions by email:&nbsp;<a href="mailto:EMAIL@leeds.ac.uk">m</a><a href="mailto:maps.pgr.admissions@leeds.ac.uk">aps.pgr.admissions@leeds.ac.uk</a>, or by telephone: +44 (0)113 343 5057.</p> <p>&nbsp;</p>


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