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Biophysics of lipid rafts: understanding the dynamic rearrangements of lipids and membrane proteins into nano-domains

PGR-P-498

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Project start date
Thursday 1 October 2020
Country eligibility
International (open to all nationalities, including the UK)
Funding
Competition funded
Supervisors
Dr Peter Adams and Dr Simon Connell
Schools
School of Physics and Astronomy
<h2 class="heading hide-accessible">Summary</h2>

The structure and physical properties of biological membranes are critical for their function as a semi-permeable external barrier for cells and an interface for communication. Membranes self-assemble from lipid molecules, forming a fluid bilayer sheet approximately 5 nanometres in thickness, and within this some lateral organisation into micro- or nano-domains is thought to occur. More commonly known as &ldquo;lipid rafts&rdquo;, these nanoscale assemblies are an enigmatic and often debated structure due to the lack of direct evidence for their existence in natural cells. Simplified model membranes with control over composition and physicochemical conditions have allowed experimental characterisation of bilayer behaviour, and high resolution microscopy of these &ldquo;Supported Lipid Bilayers&rdquo; (SLBs) show that lipid micro-domains and nano-domains do form. However, SLBs are hugely simplified models, and do not truly represent the behaviour and complexity of natural membranes. This project aims to generate more advanced model membranes which better represent biology and to quantify their biophysical properties using the most modern high-resolution techniques. This project will explore a systematic range of models to quantify which factors dominate in changing the size and shape of lipid domains. You will use a combination of Atomic Force Microscopy (AFM) to map the 3-D topography and mechanical properties of membranes at the micro- to nanoscale and fluorescence microscopy to visualize the dynamic rearrangements of membranes at scales from millimetres to micrometres. High speed AFM will provide the dynamics at the nanoscale. Firstly, you will test how lipid domains are affected by the presence of artificial point defects, by forming and then characterizing SLBs on surfaces which contain array patterns of metal nanostructures which act as solid barriers. Secondly, you will explore how bilayer structure is affected by the presence of membrane proteins, as the interplay between proteins and lipid rafts is a central unsolved research challenge. Finally, advanced single-molecule fluorescence techniques will be used to measure the rates of diffusion and specific interactions between lipids and proteins within the bilayer (time-resolved microscopy and spectroscopy). The success of this project will provide new understanding of the biophysical basis for rearrangements of complex membranes and their basis in Nature.

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

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/info/130206/applying/91/applying_for_research_degrees">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;Biophysics of lipid rafts: understanding the dynamic rearrangements of lipids and membrane proteins into nano-domains&rdquo; as well as <a href="https://eps.leeds.ac.uk/physics/staff/4103/dr-simon-connell">Dr Simon Connell</a> and <a href="https://eps.leeds.ac.uk/physics/staff/4098/dr-peter-adams">Peter Adams</a> as your proposed supervisors.</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>Funding Eligibility - UK/EU&nbsp;&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>Funding Eligibility - International Students&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>Self-funded students 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 (Simon Connell <a href="mailto:S.D.A.Connell@leeds.ac.uk">S.D.A.Connell@leeds.ac.uk</a> and Peter Adams <a href="mailto:p.g.adams@leeds.ac.uk">p.g.adams@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>


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