New pattern-recognition receptor signalling modalities in inflammation
- Project No: KIR-AfOx-06
- Intake: 2025 KIR AfOx
Pattern recognition receptors (PRR) such as toll-like receptors (TLR) and C-type lectins (CLR) are critical in shaping tissue-specific inflammatory responses, including inflammasome priming. Our research has revealed their pivotal roles in both health and chronic inflammatory diseases, and in inflammasome biology.
This project aims to unravel the complexities of pattern recognition events during inflammation by dissecting cell-type specific roles in sensing, with a focus on models of atherosclerosis and inflammation. Additionally, we will investigate how intracellular compartmentalization influences the signaling dynamics of TLRs and their capacity to prime the inflammasome.
To achieve these goals, we will employ cutting-edge single-cell technologies alongside conditional genetic deletion in vascular and immune cells. Advanced microscopy and cell signaling studies will further elucidate the functions of TLRs in health and inflammatory diseases. This comprehensive approach promises to shed new light on the sophisticated interplay of immune responses, paving the way for novel therapeutic strategies.
As a PhD candidate, you'll embark on a thrilling journey to deconstruct pattern recognition events during inflammation, focusing on cell-type specific roles and the impact of intracellular compartmentalization on TLR signaling. Your work will be instrumental in defining the role of TLRs in health and disease.
KEYWORDS
Cardiovascular
Inflammation
Homeostasis
Innate Immunity
TRAINING OPPORTUNITIES
The student will benefit from the availability of in-house state-of-the-art single cell technologies including transcriptomics and proteomics approaches using dissociative methods but also spatial methodologies including spatial transcriptomics and CyTOF Hyperion for tissue imaging in human and mouse models of atherogenesis and inflammatory conditions.
KEY PUBLICATIONS
de Winther MPJ, Bäck M, Evans P, Gomez D, Goncalves I, Jørgensen HF, Koenen RR, Lutgens E, Norata GD, Osto E, Dib L, Simons M, Stellos K, Ylä-Herttuala S, Winkels H, Bochaton-Piallat ML, Monaco C. Translational opportunities of single-cell biology in atherosclerosis. Eur Heart J. 2022 Dec 7:ehac686. doi: 10.1093/eurheartj/ehac686. PMID: 36478058.
Dib, L., Koneva, L.A., Edsfeldt, A. et al. Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications. Nat Cardiovasc Res 2, 656–672 (2023). https://doi.org/10.1038/s44161-023-00295-x
Engelen SE, Robinson AJB, Zurke YX, Monaco C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: how to proceed? Nat Rev Cardiol. 2022 Jan 31:1-21. doi: 10.1038/s41569-021-00668-4. PMID: 35102320
Buckley, C.D., Ospelt, C., Gay, S. et al. Location, location, location: how the tissue microenvironment affects inflammation in RA. Nat Rev Rheumatol 17, 195–212 (2021). https://doi.org/10.1038/s41584-020-00570-2
F. A. Fischer, L. F. M. Mies, S. Nizami, E. Pantazi, S. Danielli, B. Demarco, et al. BK1 and IKKε act like an OFF switch to limit NLRP3 inflammasome pathway activation Proceedings of the National Academy of Sciences 2021 Vol. 118 Issue 38 Pages e2009309118. DOI: doi:10.1073/pnas.2009309118
THEMES
Immunology, Cardiovascular Science.
CONTACT INFORMATION OF ALL SUPERVISORS
claudia.monaco@kennedy.ox.ac.uk
jelena.bezbradica@kennedy.ox.ac.uk
The Kennedy Institute is a proud supporter of the Academic Futures scholarship programme, designed to address under-representation and help improve equality, diversity and inclusion in our graduate student body. The Kennedy and the wider University rely on bringing the very best minds from across the world together, whatever their race, gender, religion or background to create new ideas, insights and innovations to change the world for the better. Up to 50 full awards are available across the three programme streams, and you can find further information on each stream on their individual tabs (Academic futures | Graduate access | University of Oxford).
How to Apply
Please contact the relevant supervisor(s), to register your interest in the project, and the departmental Education Team (graduate.studies@ndorms.ox.ac.uk), who will be able to advise you of the essential requirements for the programme and provide further information on how to make an official application.
Interested applicants should have, or expect to obtain, a first or upper second-class BSc degree or equivalent in a relevant subject and will also need to provide evidence of English language competence (where applicable). The application guide and form is found online and the DPhil or MSc by research will commence in October 2025.
Applications should be made to the following programme using the specified course code.
D.Phil in Molecular and Cellular Medicine (course code: RD_MP1)
For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.
Interviews to be held week commencing 13th January 2025.