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

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, physics, biology and chemistry, 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.

<p><strong>Physics and Biological Sciences at Leeds.</strong> The University of Leeds (UoL) operate low-wall&nbsp;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 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 University Grenoble Alpes, France, and may comprise extended secondments at 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> 112:557.</li> <li>G. V. Dubacheva, T. Curk, D. Frenkel and R. P. Richter (2019) Multivalent Recognition at Fluid Surfaces: The Interplay of Receptor Clustering and Superselectivity. <em>J Am Chem Soc</em> 141:2577.</li> </ol>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the Planned Course of Study that you are applying for <em><strong>PHD Physics &amp; Astronomy FT,</strong></em>&nbsp;in the research information section&nbsp;that the research degree project you wish to be considered for is <em><strong>Biological physics of cell trafficking: Immune cell homing at the blood vessel wall</strong></em>&nbsp;as well as Dr Ralf Richter&nbsp;as your proposed supervisor and in the finance section, please state clearly&nbsp;<em><strong>the funding that you are applying for, if you are self-funding or externally sponsored</strong></em>.</p> <p>Profiles:&nbsp; <a href="https://eps.leeds.ac.uk/physics/staff/4129/dr-ralf-richter">Dr Ralf Richter (Physics &amp; Astronomy)</a>, <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Dr Ralf Richter (Biological Sciences)</a></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 style="margin-bottom:11px"><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p> <p class="MsoNoSpacing">Applications will be considered on an ongoing basis. &nbsp;Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed.</p> <p class="MsoNoSpacing">Please note that you must provide the following documents in support of your application by the closing date of 3 April 2024 for Leeds Opportunity Research Scholarship or 8 April 2024 for Leeds Doctoral Scholarship:</p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> </ul>

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.

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.

<p style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants (open from October 2023). 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) (now closed for 2024/25 entry).&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> &ndash; 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 (now closed for 2024/25 entry). 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. <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>Important:</strong>&nbsp; Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are <strong>not </strong>covered under this studentship.</p> <p>Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p>

<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>)</p>