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An Interdisciplinary Research Centre at the University of Cambridge
 

Biography

Clare graduated in biochemistry before training as a vet in London.  She was funded by the Wellcome Trust for her PhD (in London) before moving to the William Harvey Research Institute for 4 years as a Wellcome postdoctoral fellow. She then moved to Cambridge as a Wellcome Trust Career Development Fellow where she is now Professor of Innate Immunity and a Wellcome Trust Investigator.

Research

Host recognition of infection

We use multidisciplinary approaches to understand how bacteria are detected by the host (through Pattern Recognition Receptors (PRRs)), but we are also studying how PRR recognition of allergen proteins or toxic proteins produced by patients link to chronic inflammatory diseases such as allergies and Alzheimer’s disease.  The host has many Pattern Recognition Receptors (PRRs), such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs), that detect bacteria, such as Salmonella entericia serovar Typhimurium, and their associated molecules (such as endotoxin).   We are studying which PRRs detect S. Typhimurium to drive an adaptive immune responses focussing on the NLRs and their effector mechanisms. We work with Pietro Cicuta (Physics) and Julia Gog (DAMPT) to study bacterial interactions with cells and respiratory tissues using mathematical modelling, optical tweezers and real-time imaging.

We are studying the molecular mechanisms underlying how ligands, such as endotoxin, interact with TLR4/MD2 receptor complex to recruit their adaptor signalling molecules, such as Mal and Tram, to initiate intracellular signalling (in collaboration with Nick Gay, Biochemistry). We are using FRET analysis and single molecule florescence techniques to study how TLRs form active signalling protein complexes and recruit adaptor proteins in real-time in live cells (in collaboration with David Klenerman, Chemistry).  Allergens, such as the cat dander protein Fel D1, are readily contaminated by endotoxin and this allows them to be detected by TLR4.  Prevention of host detection may prevent the onset of an allergic response. In particular we are interested in how allergens, such as the cat dander protein Fel d1 enhances TLR4 signalling and whether we can design inhibitors to prevent allergen recognition. Similarly other “toxic” proteins (amyloid beta and alpha synuclein) produced during diseases such as Alzheimer’s and Parkinson’s (respectively) can be recognised by TLR4 to induce inflammation and our research with David Klenerman to understand the molecular basis by which host recognition of these proteins occurs may lead to new treatments for these neuroinflammatory diseases.

 

External collaborations

Successful collaborations with academia and industry underpins all our research.  We collaborate closely with academics in the USA, Europe and Australia to stay at the cutting edge of inflammation and infection research.  A vital part of our research is to forge, and maintain, strong collaborations with the pharmaceutical industry to translate our research into medicines.  We have close links to Genentech (Clare was a visiting professor there in 2016 and 2017) and we have an ongoing collaborative research program with Vishva Dixit’s research group.  Clare is currently on secondment at GSK in Stevenage as part of their Immunology Catalyst program to forge stronger links with academia.  Clare and David Klenerman also have a drug discovery program with Apollo Therapeutics (a collaboration of Cambridge, UCL, Johnson and Johnson, Astra Zeneca and GSK) looking for novel small molecule antagonists against TLR4 as potential treatments for Alzheimer’s disease and asthma.  Clare has had collaborative grants with Zoetis Animal Health, GSK and Astra Zeneca and she currently consults for a number of biotech companies in the UK and the USA.

Publications

Key publications: 
  1. Digby, Z., Tourlomousis, P., Rooney, J., Boyle, J.P., Bibo-Verdugo, B., Pickering, R.J.,  Webster, S.J., Monie, T.P., Hopkins, L.J., Kayagaki, N., Salvesen, G.S., Warming, S., Weinert, L. and Bryant, C.E. (2021) Evolutionary loss of inflammasomes in the Carnivora and implications for the carriage of zoonotic infections.  Cell Reports 36, 109614. Doi:10.1016/j.celrep.2021.109614
  2. Tourlomousis, P., Wright, J.A.,  Bittante, A.S., Hopkins, L.J., Webster, S.J., Bryant, O.J., Mastroeni, P., Maskell, D.J., Bryant, C.E. (2020) Modifying bacterial flagellin to evade Nod-like Receptor CARD 4 recognition enhances protective immunity against Salmonella.  Nature Microbiology doi: 10.1038/s41564-020-00801-y (https://rdcu.be/cbpNC)
  3. Latty SL, Sakai J, Hopkins L, Verstak B, Paramo T, Berglund NA, Cammorota E, Cicuta PC, Gay NJ, Bond PJ, Klenerman D, Bryant CE (2018) Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub ELife pii: e31377. doi: 10.7554/eLife.31377.
  4. Pereira, M., Tourlomousis, P., Wright, J.A., Monie, T.P., Bryant, CE (2016) CARD9 negatively regulates NLRP3-induced IL-1β production upon Salmonella infection of macrophages.  Nature Communications 7:12874. doi: 10.1038/ncomms12874
  5. Man, S.M., Hopkins, L.J., Nugent, E., Cox, S., Glück, I., Tourlomousis, P., Wright, J.A., Cicuta, P., Monie, T.P. and Bryant, C.E.  (2014)  Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macro-molecular complex. Proc Natl Acad Sci 111, 7403-8. doi: 10.1073/pnas.1402911111            

Find more about Clare's research at her Google Scholar site.

 

Department of Veterinary Medicine
Innate Immunity; host recognition of infection; immunopharmacology
Professor Clare  Bryant

Contact Details

Takes PhD students
Available for consultancy

Affiliations

Classifications: 
Departments and institutes: 
Person keywords: 
Innate Immunity