... understanding life in molecular detail

Dr Dejian Zhou

Multifunctional Nanoparticle, Multivalency, FRET, Biosensing, protein-glycan interaction; Glycobiology, Nanomedicine, Bioconjugation, Cancer


We are developing a polyvalent multifunctional nanoparticle (PMN) strategy to fully exploit multivalency and unique properties of functional nanoparticles to address some important, unmet biological and biomedical chalennges: dissecting multivalent viral receptor-carbohydrate interaction mechanisms; developing ultrasensitive assays for ealy detection and diagnosis of cancer and other human diseases.

Current major projects include:
  • Dissecting multivalent viral receptor-glycan interactions
  • Ultrasensitive nanoparticle sensors for early disease diagnosis
  • Multivalent multifunctional anti-bacterial nanoparticles
  • Multifunctional anti-cancer nanomedicine

The Zhou group is pursuing a polyvalent multifunctional nanoparticle (PMN) strategy to exploit multivalency and unique properties of nanoparticles to address some important, unmet biomedical challenges: dissecting structural mechanisms of multivalent lectin-glycan interactions; developing ultrasensitive assays for early detection and diagnosis of cancer and other human diseases.

PMN-Glycan Probes

Multivalent lectin-glycan interactions are central to viral infection and regulation of immune response. However, the underpinning structural mechanisms are often poorly understood. This is evident for DC-SIGN and DC-SIGNR, two critically important tetrameric lectins which bind to viral surface sugars to enhance the HIV/Ebola infection. Despite 20 years of extensive research, their crystal structures remain to be determined, hence how their four sugar-binding-domains (CRDs) are spatially arranged remains unknown. This information is critical to design novel spatially-matched multivalent glycans to block the virus-cell binding, thereby preventing infection.

We have recently developed a new method to prepare glycan-PMNs to dissect multivalent DC-SIGN/R-glycan interactions. We revealed that QD-Man binds to DC-SIGN but not DC-SIGN/R despite their almost identical tetrameric structure (Angew. Chem. 2016). We further developed a novel multimodal readout strategy and dissected the different binding modes of DC-SIGN (tetravalent) and DC-SIGNR (bis-divalent, JACS. 2017). By combining chemistry, nanomaterials, electron microscopy and protein biochemistry techniques, we are developing a novel multidisciplinary approach to reveal their structural mechanisms, measure inter-binding site spacing, and further develop spatially matched multivalent glycans as novel, potent anti-viral therapeutic reagents (with Prof. Bruce Turnbull, Chemistry; Dr Yuan Guo, Food Science; and Dr Nicole Hondow/Prof. Rik Brydson, Chemical Engineering).

Ultrasensitive PMN sensors

The current gold standard clinical assay for protein detection is ELISA (enzyme-linked immunosorbent assays) which typically detects target on the nM-pM level (10-9-10-12 M), limiting its capacity in diagnosis of diseases at early stages where the biomarker concentrations can be 3 orders of magnitude lower. By combining the advantageous properties of nanoparticles (e.g. rapid magnetic capture, enrichment and separation of magnetic nanoparticle; stable, bright size-dependent fluorescence of quantum dot) and tight specific target binding of aptamers and/or Affimers, we are developing ultrasensitive PMN sensors capable of detecting sub-fM levels of specific disease biomarkers under clinical conditions. Such sensing technologies may allow earlier and faster diagnosis of some important diseases, such as cancer that are impossible for conventional methods (with Prof. Philip Quire, LICAP; Dr Darren Tomlinson/Prof. Mike McPherson and Prof. Peter Stockley, FBS).

Detailed research programme                  Close ▲
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Senior Lecturer in Inorganic Chemistry
BSc (Peking) PhD (Peking)
National Top 100 Excellent PhD Thesis Award, Ministry of Education, China, 1999. Young Chemists Award, Chinese Chemical Society, 1996. Award for Scientific & Technological Improvement, 2nd prize, Chin

Postdoc (Cranfield) 1997-2000
Research Associate (Cambridge) 2000-2005
Senior Research Associate (Cambridge) 2006-2007)
Senior Lecturer (Leeds) 2007-present

Chemistry 1.54
School of Biomedical Sciences
0113 343 6230
d.zhou@leeds.ac.uk

http://www.leeds.ac.uk/people/zhou.html

Selected Publications

  1. Guo Y*, Nehlmeier I, Poole E, Sakonsinsiri C, Hondow N, Brown A, Li Q, Li S, Whitworth J, Li Z, Yu A, Brydson R, Turnbull WB, Pöhlmann S, Zhou D*, "Dissecting Multivalent Lectin-Carbohydrate Recognition Using Polyvalent Multifunctional Glycan-Quantum Dots". J. Am. Chem. Soc. 2017, 139 11833-11844.

  2. Guo Y*, Sakonsinsiri C, Nehlmeier I, Fascione MA, Zhang H, Wang W, Pöhlmann S, Turnbull WB & Zhou D*. "Compact, Polyvalent Mannose Quantum Dots as Sensitive, Ratiometric FRET Probes for Multivalent Protein-Ligand Interactions." Angew. Chem. Int. Ed. 2016, 55, 4738-4742.

  3. Zhang Y,  Guo Y*, Quirke P & D. Zhou*. "Ultrasensitive single-nucleotide polymorphyism detection using target-recycled ligation, strand displacement and enzymatic amplification." Nanoscale 2013, 5, 5027-5035.

  4. Song L, Ho V. H. B., Chen C, Yang Z, Liu D, Chen R* & D. Zhou*, "Efficient pH-triggered drug delivery using a pH-responsive DNA-conjugated gold nanoparticle." Advanced Healthcare Materials 2013, 2, 275-280.