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Dr Yuan Guo

Profile

Yuan Guo obtained her doctoral degree in biophysics from the University of Basel, Switzeralnd  in 1999. She was then awarded a Swiss National Science Foundation and subsquently a Wellcome Trust Travelling Fellowship to study a  transmembrane ion channel functioning at the University of Cambridge (2000-2002). She then joined the Oxford Glycobiology Institute at the University of Oxford as a postdoctoral research fellow to investigate the structural basis for receptor-glycan specific interactions using molecular biology, biophysics and cell biology techniques (2003-2006). She moved to University of Leeds in 2007 to take up a senior research fellow position at  the School of Medicine and took a maternity career break in 2008. In 2012, she was  awarded a Wellcome Trust Re-entry Fellowship to develop glycan-nanostructures to reveal multivalent  receptor-glycan specific recognition mechanism at the School of Chemistry.  She was appointed as a lecturer in 2017. 

Yuan and her group are fascinated by the processes of immune cell specific responsing to external glycan stimulation, and use a wide reange of techniques including molecular biology, cell biology, biophysics and nanotechnology to provide new insights into the rules that governing multivalent cell surface receptor-glycan specific recognition, signal translation and immune modulation. The group is also interested in harness these understandings for therapeutic purposes including developing glycan reagents to inhibit receptor-glycan interaction mediated viral attachement to prevent viral infection,  exploiting the interaction mediated endocytosis and specific immune cell signalling protein productions to develop strategies to treat viral infection, allergy or autoimmune diseases.

Responsibilities

  • Deputy Director of Postgraduate Research

Research interests

Mechanism of multivalent receptor-glycan specific high affinity interaction

Receptor-glycan interactions mediate many important biological events. In immune system,  immune cell surface receptors binding to glycans on pathogen (virus, bacteria)  surfaces allows pathogn to be recognized to lead to immunity.  Such bindings are generally weak, so many receptors often form oligomers to cluster their carbohydrate-binding-domains (CRDs) to enhance binding affinity as strong binding observed in Velcro.  The CRDs arrangement also allow them to differentiat different glycans arrangement on cell from those on pathogen surfaces to instruct immune responses. However, the underneath mechanisms are not fully understood. 

To investigate this, we use two tetrameric receptors:  a dendritic cell (DC) surface receptor DC-SIGN and its closely-related endothelia cell surface receptor DC-SIGNR as model receptors. We have developed new glycan-nanoparticle based approaches and differentiated their different CRD arrangement and multivalent viral glycan selectivity. Combining carbohydrate synthesis, molecular biology, protein biochemistry and biophysical studies, we are further revealing the thermodynamic and kinetic insights into their multivalent binding affinity enhancement. The technique can apply to other multivalent receptor-glycan interaction study. The knowledge obtained here will guide potent, high specific receptor targeting glycan-nanoparticles development.  

We collaborate with Prof. Dejian Zhou (nanochemistry, Leeds), Prof. Bruce Turnbull (carbohydrate chemistry, Leeds), Dr. Ralf  Richter (biophysics, Leeds), Dr Liming Ying (single molecule fluorescence spectroscopy, Imperial College) and Dr Emanuele Paci (modelling, Leeds).

Elucidate how multivalent glycan-lectin stimulation manipulates immune cell dendritic cell (DC) immune function.

DC-SIGN and other receptors (e.g. mannose receptor) binding to pathogen surface glycans are exploited by some virus, bacteria and cancer cells  to evade immune surveillance. To understand how different glycan stimulation activate or inhibit immune activities, we are developing polyvalent glycan nanoparticles of similar size and glycan coatings as virus particles to mimic virus-DC interactions. We are exploiting the nanoparticles’ unique fluorescence and high density properties to reveal binding induced receptor clustering details, identify the intracellular proteins which respone the cluster formation to initiate intracellular events for DC function. Since these receptors can internalize bound glycans, the constructed nanostructures can also be tracked to study their intracellular routing. We  also conjugate antigen/allergen onto the naoparticle surface and study antigen presentation property.  Together with the measurement of binding stimulated DC cytokine production, surface co-stimulatory molecules expression,  we aim to reveal the whole picture of how glycan stimulation controls DC immune function. 

We collaborate with Prof. Stefan Pöhlmann (virology and infectious disease, Göttingen, Germany), Prof. Xiuqing Wang ( virology and immunology, South Darkota, USA)

Exploit glycan-nanoparticles for potential therapeutic treatments.

We further investigate whether our glycan-nanoparticles showing strong inhibitory effect on DC immune activation can be harnessed for potential therapeutic treatment against allergy and chronic auto-immune diseases. We are studying how glycan-nanoparticle treatments inhibit DC inflammatory cytokine production, affect allergen presentation for stimulation of T cell responses using clinical samples, paving way to the development of novel glycan-based therapeutic interventions against such chronic immune diseases incurable by current medicines.

We are also interested in exploring these nanostructure’s antigen presentation properties for potential vaccin development againest viral infection.

We collaborate with Prof. Dennis McGonagle and Dr Miriam Wittmann (Rheumatic and Musculoskeletal Medicine, Leeds), Prof. Stefan Pöhlmann (virology and Infectious disease, Göttingen, Germany) and Prof. Xiuqing Wang ( virology and immunology, South Darkota, USA)

<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://environment.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>

Qualifications

  • PhD in Biophysics
  • MSc in Bioinorganic Chemistry
  • BSc in Chemistry

Professional memberships

  • Royal Society of Chemistry

Student education

I am module leader for Food 5270M food analysis.

I presently teach Modules: Food1210: physicochemical properties of food; Food2140: food analysis; Food 3371: food product development team project; Food 5270M: food analysis

Research groups and institutes

  • Food Chemistry and Biochemistry
  • Food Safety, Security and Sustainability
<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://phd.leeds.ac.uk">research opportunities</a> allow you to search for projects and scholarships.</p>
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