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Ogg Group: Discovery of new approaches to treat skin inflammation

Supervisor: Graham Ogg 

Visual representation of a dendritic cell presenting an antigen to T-lymphocytes.© Juan Gaertner/Shutterstock.com

About the research 

 

T cells are thought to contribute to many inflammatory skin diseases, yet we still know relatively little about their antigenic targets and the key pathways involved.  This is an important question to solve if we are to find new treatments for patients.

The lab utilises molecular immunology technologies to discover T cell mechanisms and their relevance to disease.  Specifically, the lab deploys single cell and functional T cell immunology approaches to discover nodal pathways using samples from patients before and after treatment.  These human perturbation studies and functional assays are complemented by in vivo models, which are important for defining in vivo biology and progressing novel therapeutic candidates. Our data have shown that a population of overlooked “unconventional” T cells makes a major contribution to skin inflammation.  Such T cells recognise lipid antigens rather than the more studied peptide antigens. This continues to be very productive in discovery, with much interest from industry for the therapeutic applications.

Technologies used include T cell culture and functional analyses, with the associated in vitro and in vivo techniques.  As well as laboratory-based work, the lab uses single cell bioinformatic analyses for transcriptomic outputs and T cell receptor sequencing, as well as CRISPR-mediated gene editing.  The lab is very “translational” with a deep and successful drive to progress the therapeutic applications, including many patents, licenses, as well as spin-outs.

This project is not suitable for part-time research. 

Training Opportunities 

The candidate will learn human tissue T cell identification, culture and functional analyses, as well as single cell analyses such as spatial transcriptomics and CITE-seq.  The project will likely involve CRISPR-mediated gene editing and use of in vivo inflammation models to define biology and progress therapeutic assets.  Experience will also be gained in the patenting process and engagement with industry partners.  These are skills which are transferable and valuable, which will enable a career across disciplines and therapeutic modalities.

Students will be enrolled on the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Additional Supervisors

1. Alison Simmons

2. Karmella Naidoo

Publications 

1

Chen YL, Ng JSW, Ottakandathil Babu R, Woo J, Nahler J, Hardman CS, Kurupati P, Nussbaum L, Gao F, Dong T, Ladell K, Price DA, Duncan DA, Johnson D, Gileadi U, Koohy H, Ogg GS. Group A Streptococcus induces CD1a-autoreactive T cells and promotes psoriatic inflammation. Sci Immunol. 2023 Jun 8;8(84):eadd9232. doi: 10.1126/sciimmunol.add9232.

2

Hardman CS, Chen YL, Wegrecki M, Ng SW, Murren R, Mangat D, Silva JP, Munro R, Chan WY, O'Dowd V, Doyle C, Mori P, Popplewell A, Rossjohn J, Lightwood D, Ogg GS. CD1a promotes systemic manifestations of skin inflammation. Nat Commun. 2022 Dec 7;13(1):7535. doi: 10.1038/s41467-022-35071-1.

3

Huang S, Shahine A, Cheng TY, Chen YL, Ng SW, Balaji GR, Farquhar R, Gras S, Hardman CS, Altman JD, Tahiri N, Minnaard AJ, Ogg GS, Mayfield JA, Rossjohn J, Moody DB. CD1 lipidomes reveal lipid-binding motifs and size-based antigen-display mechanisms. Cell. 2023 Oct 12;186(21):4583-4596.e13. doi:10.1016/j.cell.2023.08.022.

4

Cotton RN, Wegrecki M, Cheng TY, Chen YL, Veerapen N, Le Nours J, Orgill DP, Pomahac B, Talbot SG, Willis R, Altman JD, de Jong A, Van Rhijn I, Clark RA, Besra GS, Ogg G, Rossjohn J, Moody DB. CD1a selectively captures endogenous cellular lipids that broadly block T cell response. J Exp Med. 2021 Jul 5;218(7):e20202699. doi: 10.1084/jem.20202699.

5

Ogg GS, Rossjohn J, Clark RA, Moody DB. CD1a and bound lipids drive T-cell responses in human skin disease. Eur J Immunol. 2023 Oct;53(10):e2250333. doi: 10.1002/eji.202250333.
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