Developing novel glycan-nanoparticle probes to elucidate dendritic cell immune modulation mechanisms

Lectins are glycan binding proteins on immune cells that differentiate glycan patterns between normal and pathogens/disease cells to activate immune responses for protection. Evidence suggests that lectins, instead of specializing individually for pathogen or healthy cell glycan recognition, work cooperatively to complete tasks. Hence, a relatively small number of lectins can differentiate many pathogens or diseases/healthy cells to fine tune immune responses. However, the relationship between lectin combination and immune actions and how different lectin combinations modulate immune cell responses remains unclear. Moreover, it has been found that some pathogens (e.g., HIV) and cancer cells can exploit their glycan patterns to evade immune surveillance. Hence, revealing the relationship and underlying modulation mechanisms will not only advance our fundamental understanding of this important biological process but also guide the development of effective interventions against viral infection and cancer.<br /> We have recently pioneered a powerful glycan-nanoparticle (NP) probe for successfully elucidating DC-SIGN- (a key DC surface immune lectin) glycan multivalent binding mechanisms. Here, we will extend our glycan-NP probe at the cellular level, exemplified using dendritic cell (DC), the most important pathogen presenting cell to dictate immune response. We will construct glycan-NPs with structures mimicking those of pathogens and/or healthy cells and use them to stimulate and measure DC immune responses. We will then pull down all glycan-NP bound lectins conveniently, via centrifugation facilitated by NP’s high density, and identify the lectins involved by mass spectroscopy. Combing the results will allow us to establish the correlation between lectin engagement and DC immune function regulation, using lectins’ native glycan instead of artificial antibody ligands. Moreover, the glycan-NP pull-down can also identify intracellular signalling proteins bound to the engaged lectins. Such proteins are directly involved in DC functioning. Together, these results will allow us to elucidate DC immune modulation mechanisms upon glycan-stimulation.<br /> <br /> In this project, you will join a vibrant and highly stimulating research environment within the renowned Astbury Center for Structural Molecular Biology at the University of Leeds. You will receive training on organic ligand synthesis, glycan-NP construction and characterization, cell culture, and mass spectroscopy.<br /> As a candidate, you will preferably have interests in exploring novel hypotheses and multidisciplinary techniques to reveal biological details. Ideally, you will have a strong background in synthetic chemistry or chemical biology. Knowledge of nanochemistry, protein biochemistry, protein mass spectroscopy, and/or cell culture will be advantageous. Motivation, creativity, excellent communication and team working skills are highly desirable.<br />

<p style="text-align:justify; margin-bottom:11px">C-type lectins are glycan binding proteins on immune cells, which can differentiate glycan patterns between self (normal cells) and foreign (pathogens/disease cells) ones to activate immune responses for protection or elimination. Each immune cell, including dendritic cells (DCs) and macrophages, is decorated with a set of different lectins. Recent evidence suggests that lectins instead of specialized for pathogen or healthy cells glycans recognition, they work cooperatively to complete their tasks. In this way, a relatively small number of lectins can differentiate many pathogens or diseases/healthy cells to fine tune immune responses. However, the relationship between lectin combination and immune actions and how different lectin combination modulates immune cell responses remain unclear. Moreover, it has been found that some pathogens (e.g., HIV) and cancer cells can exploit their glycan patterns to interact with some immune lectins to evade immune surveillance or facilitate cancer development, Hence, revealing the relationship and underlying mechanisms will not only advance our fundamental understanding of this important biological process but also guide the development of effective interventions against viral infection and cancer.</p> <p style="text-align:justify; margin-bottom:11px">We have recently pioneered a powerful glycan-nanoparticle (NP) probe for successfully elucidating DC-SIGN- (a key DC surface immune lectin) glycan multivalent binding mechanisms at the molecular level. Here, we will extend our glycan-NP probe method to study multivalent lectin-glycan interactions at the cellular level, exemplified using DCs, the most important pathogen presenting cell to dictate immune response. We will construct glycan-NPs with structures mimicking those of pathogens and/or healthy cells and use them to stimulate and measure DC immune responses. We will then pull down all glycan-NP bound lectins conveniently, via centrifugation facilitated by NP’s high density, and identify the lectins involved by mass spectroscopy. Combing the result will allow us to establish the correlation between lectins engagement and DC immune function regulation, using DC-SIGN’s native glycan ligands, removing the potential artefacts induced by antibody-based pull-down probes widely used in literature. Moreover, the glycan-NP pull-down can also identify intracellular signalling proteins bound to the engaged lectins. Such proteins are directly involved in DC functioning. Together, these results will allow us to elucidate DC immune modulation mechanisms upon glycan-stimulation.</p> <p style="text-align:justify; margin-bottom:11px">In this project, you will join a vibrant and highly stimulating research environment within the renowned<span style="font-size:11pt"><span style="line-height:107%"><span style="font-family:Aptos,sans-serif"><span style="font-family:"Calibri",sans-serif"> </span></span></span></span><a href="https://www.findaphd.com/common/clickCount.aspx?theid=160390&type=184&DID=735&url=https%3a%2f%2fastbury.leeds.ac.uk%2f" target="_blank">Astbury Centre for Structural Molecular Biology</a> at the University of Leeds. You will work alongside others in glycoscience (<a href="https://environment.leeds.ac.uk/food-nutrition/staff/7394/professor-yuan-guo">Guo</a>), nanochemistry (<a href="https://eps.leeds.ac.uk/chemistry/staff/4199/professor-dejian-zhou">Zhou</a>) and mass spectrometry (<a href="https://eps.leeds.ac.uk/chemistry/staff/15436/dr-hannah-britt">Brit</a>) labs. The Guo/Zhou groups pioneered the glycan-NP multifunctional probes for studying multivalent lectin-glycan interactions. You will receive trainings on organic ligand synthesis, glycan-NP construction and characterization, cell culture, and mass spectroscopy.</p> <p style="text-align:justify; margin-bottom:11px"> </p>

<p paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{113}" paraid="1539768372"><strong>You must contact the proposed supervisor for this project before you make a formal application. </strong></p> <p paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{119}" paraid="1895649428">A formal application for research degree study should then be made online through the <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees" rel="noreferrer noopener" target="_blank">University's website</a>. You will need to create a login ID with a username and PIN: </p> <ul> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{125}" paraid="1717955186">For ‘Application type’ please select ‘Research Degrees – Research Postgraduate’. </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{131}" paraid="1941411394">The admission year for this project is 2026/27 Academic Year.   </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{137}" paraid="1823221166">You will need to select your ‘Planned Course of Study’ from a drop-down menu. For this project, scroll down and select ‘PhD Food Science and Nutrition Full-time’.   </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{143}" paraid="754352421">The project start date for this project is October 2026, please use this as your Proposed Start Date of Research. </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{149}" paraid="202248598">Please state clearly in the research information section that the research degree you wish to be considered for is ‘Developing novel glycan-nanoparticle system to elucidate dendritic cell immune modulation mechanism’ as well as <a href="https://environment.leeds.ac.uk/food-nutrition/staff/7394/professor-yuan-guo">Professor Yuan Guo</a> as your proposed supervisor. </li> </ul> <p paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{155}" paraid="812110430">If English is not your first language, you must provide evidence that you meet the University's minimum English language requirements (below). </p> <p paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{161}" paraid="1891516213">More information on how to apply is available on our website <a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees" rel="noreferrer noopener" target="_blank">here</a>. You will need to provide copies of the following documents: </p> <ul> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{172}" paraid="1858125611">a personal statement for this project</li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{178}" paraid="877561217">your CV </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{184}" paraid="1448270499">certificates and transcripts of all academic qualifications </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{190}" paraid="932080590">English language qualification certificates </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{196}" paraid="1315959137">visa and immigration documents, if applicable </li> <li paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{202}" paraid="226045984">funding information – sources of funding that you are applying for (e.g. government scholarship), or if you are able to pay your own fees and maintenance  </li> </ul> <p paraeid="{cc558561-e300-45f5-a898-3bd20c9a5968}{208}" paraid="1308150127"><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>

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.

For start dates from September 2026, the minimum English language entry requirement for research postgraduate research study in the School of Food Science and Nutrition 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.

<p paraeid="{3d04e34c-3522-40f3-8630-c6f14cbc41d0}{143}" paraid="557166827"><strong>This is not a funded project, but you can apply for funding separately. Self-funding students are also welcome to apply. </strong></p> <p paraeid="{3d04e34c-3522-40f3-8630-c6f14cbc41d0}{149}" paraid="1936376053"><strong>Please note that in addition to the <a href="https://www.leeds.ac.uk/research-fees/doc/research-degrees-fees" rel="noreferrer noopener" target="_blank">tuition fee</a> for the programme there will also be a <a href="https://www.leeds.ac.uk/research-fees/doc/postgraduate-research-bench-policy" rel="noreferrer noopener" target="_blank">bench fee</a> of £10,000 per year for this project.   </strong></p> <p paraeid="{3d04e34c-3522-40f3-8630-c6f14cbc41d0}{171}" paraid="1993701339">Funding opportunities for Home students – The <a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2026" rel="noreferrer noopener" target="_blank">Leeds Doctoral Scholarship</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2026" rel="noreferrer noopener" target="_blank">Leeds Opportunity Research Scholarship</a> are available to UK applicants.  <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary" rel="noreferrer noopener" target="_blank">Alumni Bursary</a> is available to graduates of the University of Leeds. </p> <p paraeid="{3d04e34c-3522-40f3-8630-c6f14cbc41d0}{194}" paraid="629442306">Funding opportunities for International students –The <a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021" rel="noreferrer noopener" target="_blank">China Scholarship Council - University of Leeds Scholarship</a> is available to nationals of China. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary" rel="noreferrer noopener" target="_blank">Alumni Bursary</a> is available to graduates of the University of Leeds. </p>

<p>For further information regarding the project, please contact the supervisors Professor Yuan Guo (<a href="mailto:y.guo@leeds.ac.uk">y.guo@leeds.ac.uk</a>) or Professor Dejian Zhou (<a href="mailto:d.zhou@leeds.ac.uk">d.zhou@leeds.ac.uk</a>). You must contact the supervisors before making a formal application.</p>