Periodic Reporting for period 1 - DC-SIGN-MFN (Dissecting Multivalent Viral Receptor-carbohydrate Interactions Using Polyvalent Multifunctional Glycan-Quantum Dot)
Reporting period: 2018-07-13 to 2020-07-12
This fellowship aims to develop a novel multimodal readout strategy (combining FRET, TEM and particle size analysis) using compact glycan-quantum dots (QDs) by exploiting multivalency and QD’s strong fluorescence and high contrast in TEM imaging. By tuning glycan structure, valency, inter-glycan spacing, it aims to create a perfect spatial & orientation match to those of glycan-binding-domains (CRDs) in DC-SIGN/R, leading to greatly enhanced binding affinity. By studying QD-glycans and their assemblies binding with DC-SIGN/R, we will reveal key structural data (e.g. CRD orientation, distance, binding mode) in DC-SIGN/R. It also aims to verify the binding data with native receptors on cell surfaces, correlate receptor binding affinity with virus inhibition potency, and study their immune cell activation.
The fellow has received extensive trainings in ligand synthesis, protein production, labelling and FRET assays, as well as project management and grant writing skills. The fellow has also participated in supervising MChem and MSc students and received significant support from technical staff and other lab members. The fellow has collaborated with other group members to produce two research papers as co-author. The fellow prepared drafts, figures for publications, and participated weekly group meetings and monthly discussions.
(1) Wang, W., Kong, Y., Jiang, J., Tian, X., Li, S., Akshath, U.S. Tiede, C., Hondow, N., Yu, A., Guo, Y. and Zhou, D. Nanoscale, 2020,12(16), pp.8647-8655.
(2) Budhadev, D., Poole, E., Nehlmeier, I., Liu, Y., Hooper, J., Kalverda, E., Akshath, U.S. Hondow, N., Turnbull, W.B. Pöhlmann, S., Guo, Y., and Zhou, D. J. Am. Chem. Soc. 2020, 142(42), 18022-18034.
(1) U.S. Akshath, D. Budhadev, E. Kalverda, N. Hondow, W. B. Turnbull, Y. Guo and D. Zhou. Probing multivalent lectin-glycan interactions using multifunctional glycan-nanoparticles, Poster-Nanolithography of Biointerfaces Faraday Discussion, London, UK, 3-5/7/2019
(2) D. Budhadev, E. Poole, I. Nehlmeier, Y. Liu, E. Kalverda, J. Hooper, U. S. Akshath, W. B. Turnbull, S. Pöhlmann, Y. Guo and D. Zhou. Polyvalent Glycan-Nanoparticles as Multifunctional Structural Probes for Viral Receptors, DC-SIGN and DC-SIGNR. Poster- European Symposium on Biological and Organic Chemistry, 53rd ESBOC Symposium, Gregynog, UK, 17-19/5/2019.
(3) D. Budhadev, E. Poole, I. Nehlmeier, Y. Liu, E. Kalverda, J. Hooper, U. S. Akshath, W. B. Turnbull, S. Pöhlmann, Y. Guo and D. Zhou. Probing and Blocking DC-SIGN/R-glycan Interaction Mediated Virus Infection Using Polyvalent Multifunctional Glycan Gold Nanoparticles. Oral presentation- RSC Carbohydrate Early Career Researcher Webinar Series, Oral, 2/7/2020.
It should be noted that this project has been focused on elucidating fundamental mechanisms underlying MLGIs, and establish new approaches and design rules for potent, specific lectin targeting. It is not focused on developing new products or medicines directly. However, the new tools and findings obtained from this study will likely to benefit human healthcare, the UK/EU pharmaceutical industries and provide socio-economic impact over the medium to long term (e.g. 5-15 years).
The new findings have been highlighted on the group research website and also the group tweeter account @ZhouDejian.