Superselective targeting of cancer and neuronal cells using multivalent lectin-glycan interactions

Are you keen to progress research in glycoscience, at the interface between chemistry, biology and physics, and interested in developing a new type of probes for diagnostics and targeted drug delivery? This project may be for you!<br /> <br /> Glycocalyces are glycan-rich coats that surround virtually every cell in our body. They are essential for multicellular life and instrumental for cells to communicate with their environment. How cells use their surface glycans to communicate, however, remains a major open question in biology. Many cell types express a similar set of glycans, and it is the relative abundance of glycan epitopes, rather than the mere presence of a given epitope, that differentiates one cell type from another.<br /> <br /> This project aims to develop &lsquo;superselective&rsquo; glycocalyx probes that are not only able to recognise a specific glycan epitope, but additionally are also exquisitely sensitive to the density of glycans expressed on the cell surface. If successful, these probes will be able to diagnose and target specific cell types, such as cancer cells, with exquisite selectivity.<br /> <br /> We have recently demonstrated that multivalent probes based on a flexible polymer scaffold can effectively discriminate surfaces based on the density of surface receptors (Dubacheva et al, Acc Chem Res, 2023, 56:729). In this project, you will develop superselective probes based on lectins (glycan-binding proteins) and polymer scaffolds and demonstrate how these can be used to analyse the glycocalyx of cells, such as cancer cells, neurons or the endothelial cells that line the inner walls of our blood vessels. To this end, you will combine synthetic and bio-orthogonal chemistry with protein biochemistry, cell biology and biophysical techniques. The team of supervisors and collaborators will provide the ideal training environment for this multi-disciplinary project.<br /> <br /> By demonstrating feasibility of superselective recognition of selected cell types, this project has the potential to transform the new superselectivity concept into a technology for a wide range of applications, including targeted drug delivery, cell sorting and in vivo imaging and cell diagnosis.<br /> <br /> This work is supported by a multi-disciplinary team of supervisors with expertise in all research areas relevant to this project. Excited by this project? Please contact the supervisors for more information before submitting your application.

<p class="MsoCommentText" style="margin-bottom:11px"><strong>Supervisors and collaborations</strong>. This project will be jointly supervised by <a href="https://eps.leeds.ac.uk/chemistry/staff/4194/professor-bruce-turnbull">Prof. Bruce Turnbull</a> in the <a href="https://eps.leeds.ac.uk/chemistry-research-innovation">School of Chemistry</a>&nbsp; (Faculty of Mathematics and Physical Sciences), and <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/129/dr-ralf-richter">Dr. Ralf Richter</a> who belongs to the <a href="https://mnp.leeds.ac.uk">Molecular and Nanoscale Physics Group</a> in the <a href="https://eps.leeds.ac.uk/physics-research-innovation">School of Physics and Astronomy</a> (Faculty of Mathematics and Physical Sciences), and to the <a href="https://biologicalsciences.leeds.ac.uk/homepage/85/school_of_biomedical_sciences">School of Biomedical Sciences</a> (Faculty of Biological Sciences). The Turnbull and Richter Labs are also part of the cross-disciplinary <a href="https://astbury.leeds.ac.uk">Astbury Centre for Structural Molecular Biology</a> and the <a href="https://www.leeds.ac.uk/bragg-centre-materials-research">Bragg Centre for Materials Research</a>.</p> <p>The post will involve collaborations with <a href="https://biologicalsciences.leeds.ac.uk/school-biomedical-sciences/staff/99/dr-jessica-cf-kwok">Dr. Jessica Kwok</a> in the <a href="https://biologicalsciences.leeds.ac.uk/homepage/85/school_of_biomedical_sciences">School of Biomedical Sciences</a>, and with <a href="https://eps.leeds.ac.uk/physics/staff/4107/professor-stephen-evans">Prof. Stephen Evans</a> in the <a href="https://eps.leeds.ac.uk/physics-research-innovation">School of Physics and Astronomy</a>. All these collaborations are already well established.</p> <p><strong>Relevant references</strong></p> <ol> <li> <p>G. V. Dubacheva, T. Curk and R. P. Richter 2023. Determinants of Superselectivity - Practical Concepts for Application in Biology and Medicine. Acc Chem Res 56:729-739.</p> </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 research information section&nbsp;that the research degree project you wish to be considered for is Superselective cell targeting through multivalent lectin-glycan interactions as well as <a href="https://eps.leeds.ac.uk/chemistry/staff/4194/professor-bruce-turnbull">Prof. Bruce Turnbull</a> and <a href="https://eps.leeds.ac.uk/physics/staff/4129/dr-ralf-richter">Dr. Ralf Richter </a>as your proposed supervisors. <strong>Please apply to the School of Physics and Astronomy</strong>.&nbsp;&nbsp;</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>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">The closing date for applications is 9<span style="font-size:10.8333px"> </span>June 2023. Potential applicants are encouraged to contact the supervisors for an informal discussion before making a formal application.</p> <p>Please note that you must provide the following documents in support of your application by the closing date of 9 June 2023:</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> <li>Funding information</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 class="MsoNoSpacing">A highly competitive Externally Funded Studentship in support of a BBSRC grant, consisting of the award of fees at the UK fee rate together with a maintenance grant of &pound;18,622 for 3 years.</p> <p>This opportunity is open to UK applicants only. All candidates will be placed into the Studentship Competition and selection is based on academic merit.<br /> <br /> Please refer to the&nbsp;<a href="https://www.ukcisa.org.uk/">UKCISA</a>&nbsp;website for&nbsp;information regarding Fee Status for Non-UK Nationals.</p> <p><strong>Self-funded students and externally sponsored students are also very welcome to apply.</strong></p> <p>&nbsp;</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>) and Prof. Bruce Turnbull (<a href="mailto:w.b.turnbull@leeds.ac.uk">w.b.turnbull@leeds.ac.uk</a>) for further information.</p> <p>For further information about your application, please contact Doctoral College Admissions (<a href="mailto:maps.pgr.admisssions@leeds.ac.uk">maps.pgr.admisssions@leeds.ac.uk</a>)</p> <p>&nbsp;</p> <p>&nbsp;</p>