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Kennedy Trust Prize Studentships

Overview

The germinal centre (GC) reaction is responsible for the production of high-affinity antibodies and immune memory. It is vital for an effective humoral immune response, for example following vaccination. However, it also drives many autoimmune diseases, including lupus. 

There is a growing understanding that metabolic state can profoundly influence the outcome of the immune response, through mechanisms still under exploration. However, how immune metabolism varies at the single-cell level, in time and space, in vivo, and in disease, is almost unknown. The germinal centre is a tightly spatiotemporally co-ordinated immune process, but very little is known about its metabolism, despite its important role in health and disease. 

In this project, we will use a combination of experimental techniques to explore the metabolism of the GC in patients with lupus, and model our findings in transgenic and autoimmune-prone mice, with the aim of developing new therapeutic approaches. 

Approach and training

The project combines techniques of advanced immunology, optical imaging, and disease modelling, with cutting-edge metabolism analysis; training will be provided for all these approaches. An important component of the project is the use of mass spectrometry imaging (MSI) in an interdisciplinary collaboration with Prof Josephine Bunch at the National Centre of Excellence in MSI at the National Physical Laboratory, London. The candidate would have the opportunity to access the highly advanced facilities there, and develop expertise in the bioinformatic analysis of MSI data. The Kennedy Institute is a world-renowned research centre, housed in a brand new, state-of-the-art facility. 

A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology, data analysis and the microbiome. Students will attend regular seminars within the department and those relevant in the wider University. Students will be expected to present data regularly in the departmental PGR seminars, in the Clarke and Cornall groups,and to attend external conferences to present their research globally. 

Students will also have the opportunity to work closely with the Cornall Group. 

Publications

  1. Clarke AJ et al. B1a B cells require autophagy for metabolic homeostasis and self-renewal. J Exp Med2018. DOI: 10.1084/jem.20170771
  2. Boothby M and Rickert RC. Metabolic regulation of the immune humoral response. Immunity2017. DOI: 10.1016/j.immuni.2017.04.009
  3. De Silva NS and Klein U. Dynamics of B cells in germinal centresNat Rev Immunol2015. DOI: 10.1038/nri3804
  4. Passarelli MK et al. The 3D OrbiSIMS – label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nature Methods. 2017. DOI: 10.1038/nmeth.4504

Themes

  • Immunology
  • Molecular, Cell and Systems Biology
  • Translational Medicine and Medical Technology

HOW TO APPLY

The department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisor(s) or the Directors of Graduate Studies who will be able to advise you of the essential requirements.

Interested applicants should have or expect to obtain a first or upper second class BSc degree or equivalent, and will also need to provide evidence of English language competence. The University requires candidates to formally apply online and for their referees to submit online references via the online application system.

The application guide and form is found online and the DPhil or MSc by research will commence in October 2019.

When completing the online application, please read the University Guide.

Further information

Contact Dr Alex Clarke, Kennedy Institute, University of Oxford

 

External supervisor

Project reference number #201905

PROJECTS

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