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

PGR-P-1818

Key facts

Type of research degree: PhD
Application deadline: Monday 29 April 2024
Project start date: Tuesday 1 October 2024
Country eligibility: UK only
Funding: Competition funded
Source of funding: Doctoral training partnership
Supervisors: Professor Bruce Turnbull
Additional supervisors: Dr Ralf Richter (Physics)
Schools: School of Chemistry, School of Physics and Astronomy

<h2 class="heading hide-accessible">Summary</h2>

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! 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. This project aims to develop ‘superselective’ 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. 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 new polymer scaffolds for superselective probes based on lectins (glycan-binding proteins) 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 to develop new probes, and evaluate them using cell biology and biophysical techniques. The team of supervisors and collaborators will provide the ideal training environment for this multi-disciplinary project. 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. 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.

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

Supervisors and collaborations. 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> (Faculty of Engineering 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 Engineering 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>. 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. Relevant references <ol> <li> 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. </li> </ol>

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

Formal applications for research degree study should be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University's website</a>. Please state clearly in the Planned Course of Study section that you are applying for EPSRC DTP Engineering & Physical Sciences (if you do not apply to this programme code, your application will not be considered) and in the research information section that the research degree you wish to be considered for is Superselective targeting of cancer and neuronal cells using multivalent lectin-glycan interactions as well as <a href="https://eps.leeds.ac.uk/chemistry/staff/4194/professor-bruce-turnbull">Professor Bruce Turnbull</a> as your proposed supervisor. Please state in the Finance section that the funding source you are applying for is EPSRC Doctoral Training Partnership 2024/25:  Chemistry. If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below). 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. Applications will be considered after the closing date.  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. 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, 8 April 2024 for Leeds Doctoral Scholarship or 29 April 2024 for EPSRC DTP: <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>

<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>

UK Only A highly competitive EPSRC Doctoral Training Partnership Studentship offering the award of fees, together with a tax-free maintenance grant of £19,237 per year for 3.5 years.  Training and support will also be provided. This opportunity is open to UK applicants only.  All candidates will be placed into the EPSRC Doctoral Training Partnership Studentship Competition and selection is based on academic merit. The <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). <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds. Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals. Self-Funded or externally sponsored students are welcome to apply. Non-UK –The <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> is available to nationals of China (now closed for 2024/25 entry). The <a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a> 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. Important:  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 not covered under these studentships. Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.

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

For further information about this project, please contact Professor Bruce Turnbull by email to <a href="mailto:W.B.Turnbull@leeds.ac.uk">W.B.Turnbull@leeds.ac.uk</a> For further information about your application, please contact Doctoral College Admissions by email to <a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a>

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