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Biological physics of cell trafficking: Immune cell homing at the blood vessel wall

PGR-P-496

Key facts

Type of research degree
PhD
Application deadline
Ongoing deadline
Project start date
Friday 1 October 2021
Country eligibility
International (open to all nationalities, including the UK)
Funding
Competition funded
Supervisors
Dr Ralf Richter
Schools
School of Biomedical Sciences, School of Physics and Astronomy
Research groups/institutes
Integrative Membrane Biology, Molecular and Nanoscale Physics
<h2 class="heading hide-accessible">Summary</h2>

Cell trafficking is vital to all multicellular life and key in diseases such as cancer. In this PhD project, you will devise new methods to study how immune cells that circulate in the blood stream find and bind to sites of inflammation and how cancer cells hijack the system to metastasize. This is a formidable challenge that requires multiple disciplines &amp;ndash; physics, biology and chemistry &amp;ndash; to work hand in hand.<br /> <br /> A key factor in this process are specialised receptor molecules on the surface of the circulating cells that recognize a polysaccharide-rich coat lining the blood vessel walls. The mechanical properties of the receptors and the blood vessel coat are critical for proper adhesion under the shear stress of blood flow. Yet, what these are and how they control selective cell trafficking is not well understood.<br /> <br /> A key technique to probe the nanomechanics of individual molecular bonds along with the mechanical properties of tissues is atomic force microscopy (AFM). Laminar flow assays and optical microscopy, on the other hand, enable collective interactions to be probed. In a multidisciplinary environment, you will learn to create bottom up biosynthetic models of the circulating cell-blood vessel interface that enable well defined biophysical experiments using AFM and optical microscopy. The experimental work will be accompanied by theoretical work to aid the analysis of the experimental data and develop an understanding of the molecular and soft matter physics underpinning selective cell trafficking.<br /> <br /> In this project, you will put soft matter physics to the benefit of understanding biology. This will provide new insight into how cells trafficking is regulated, and ultimately help to devise new strategies to interfere with diseases such as cancer and chronic inflammation, and to design advanced biomaterials that guide cells for tissue repair.<br /> <br /> Suitable CANDIDATES would have a background in biophysics, soft matter physics, physical chemistry, biomedical engineering or a closely related field, and keen interest in multidisciplinary work. Experience in single molecule biophysics or advanced optical microscopy is an advantage.

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

<p><strong>Physics and Biological Sciences at Leeds.</strong> The University of Leeds (UoL) operate &lsquo;low-wall&rsquo; principles with the aim of encouraging cross-disciplinary approaches to big science questions. This project will take place in the&nbsp;<a href="https://eps.leeds.ac.uk/physics-research-groups/doc/molecular-nanoscale-physics">Molecular and Nanoscale Physics Group</a>&nbsp;within the <a href="https://eps.leeds.ac.uk/physics">School of Physics and Astronomy</a>, in tight collaboration with&nbsp;the <a href="https://biologicalsciences.leeds.ac.uk/">Faculty of Biological Sciences</a>. The <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Richter Lab</a> is also part of the <a href="https://www.leeds.ac.uk/info/130565/bragg_centre_for_materials_research">Bragg Centre for Materials Research</a>, and the <a href="https://www.astbury.leeds.ac.uk/">Astbury Centre for Structural Molecular Biology</a>.&nbsp;This environment offers&nbsp;superb facilities, provides a high quality research training&nbsp;and delivers an exceptional student education.</p> <p><strong>Collaboration with University Grenoble Alpes (France).</strong> The successful applicant will be hosted by the <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Richter Lab</a> at UoL. This project is part of an ongoing collaboration with the&nbsp;University Grenoble Alpes (UGA). He/she will work under the supervision of Dr. Ralf Richter (UoL) and Dr. Delphine D&eacute;barre at the Laboratory of Interdisciplinary Physics (LIPhy; research group <a href="https://www-liphy.univ-grenoble-alpes.fr/MC2-1249?lang=en">Mechanics of Cells in Complex Media</a>) at UGA.&nbsp;The project will comprise extended secondments to LIPhy.</p> <p><strong>References</strong></p> <ol> <li>H. S. Davies, D. Debarre, N. El Amri, C. Verdier, R. P. Richter and L. Bureau (2018) Elastohydrodynamic lift at a soft wall. <em>Phys Rev Lett</em> 120:198001.</li> <li>F. Bano, S. Banerji, M. Howarth, D. G. Jackson and R. P. Richter (2016) A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force. <em>Sci Rep </em>6:34176.</li> <li>G. V. Dubacheva, T. Curk, R. Auz&eacute;ly-Velty, D. Frenkel and R. P. Richter (2015) Designing Multivalent Probes for Tunable Superselective Targeting. <em>Proc Nat Acad Soc USA</em> 112:5579</li> </ol> <p>The earliest start date for this project is 1&nbsp;October 2021.&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="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;Biological physics of cell trafficking: Immune cell homing at the blood vessel wall&rsquo;&nbsp;as well as <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Dr Ralf Richter</a>&nbsp;as your proposed supervisor.</p> <p>In&nbsp;your application, please include a a&nbsp;motivation letter on why you want to join the project, a CV, transcripts of your university record, and contact details of two referees.</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>UK</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/138-leeds-doctoral-scholarships-2021-january-deadline">Leeds Doctoral Scholarship (January deadline)</a>&nbsp;and the&nbsp;<a href="https://phd.leeds.ac.uk/funding/141-henry-ellison-scholarship-2021">Henry Ellison Scholarship</a>&nbsp;are available to UK applicants. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP).&nbsp; <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Non-UK</strong>&nbsp;&ndash; The&nbsp;<a href="https://phd.leeds.ac.uk/funding/63-school-of-physics-astronomy-fee-only-scholarship">School of Physics &amp; Astronomy Fee Only Scholarship</a>&nbsp;is available to support the additional academic fees of international applicants. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a>&nbsp;is available to nationals of China. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is also available to international applicants and supports those who are from groups that are currently under-represented in physics (awarded by the IOP). <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Self-Funding Students </strong>are also welcome to apply.</p>

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

<p>Individuals interested in this project are encouraged to contact Dr. Ralf Richter (<a href="mailto:r.richter@leeds.ac.uk">r.richter@leeds.ac.uk</a>) for further information.&nbsp;We are always happy to discuss scientific questions with pro-active candidates.</p> <p>For questions related to the application process and eligibility, please contact Doctoral College Admissions by email (<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions</a><a href="mailto:EMAIL@leeds.ac.uk">@leeds.ac.uk</a>) or by phone (+44 (0)113 343 5057).</p>


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