About the Project
Iron is critical for life: too little can halt DNA synthesis and energy metabolism; but too much can generate toxic reactive oxygen species. Furthermore, iron is an essential nutrient for the growth of pathogens, but is also required for the immune system that fights infections. For example, during infection the host sequesters iron in an attempt to starve pathogens as part of the innate immune response, while T cells and B cells need iron for their function to clear infections.
The hormone hepcidin controls the amount and distribution of iron in the body; expression of hepcidin is controlled by a combination of iron concentration in the body, inflammation, and the requirement for iron to make red blood cells. We have made significant contributions to understanding how hepcidin and iron are controlled in health and disease, including iron deficiency, thalassaemia, HIV, HCV, typhoid fever, Influenza virus infection, and most recently COVID19. We utilise experimental models of key diseases, including malaria and tumour models, and manipulate hepcidin to test how controlling iron homeostasis influences immune responses and the course of disease.
Future work will look at how iron availability influences adaptive immunity, in terms of a) how iron is trafficked within lymph nodes and the spleen to ensure supply for lymphocytes; b) how iron acquisition by lymphocytes and their haematopoietic progenitors influences cellular metabolism, differentiation and function; c) how iron availability impacts the immune response to vaccines, protection from infections, autoimmunity, and immunotherapy of cancer.
Additional Supervision may be provided by Paul Klenerman (NDM, Oxford) and Simon Draper (NDM, Oxford)
Students will be trained to utilise flow and mass cytometry, animal models of altered iron metabolism, infection and immunity, a portfolio of in vitro cell culture assays and analytical methodology, statistical approaches, and will have access to the WIMM imaging facilities and bioinformatics centre. We also undertake collaborations overseas especially with the MRC Unit in The Gambia and students will have the opportunity to travel there depending on the nature of the project undertaken.
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.
All WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds 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.
For October 2021 entry, the application deadline is 8th January 2021 at 12 noon midday, UK time.
Please visit our website for more information on how to apply.
Lim PJ et al. Nrf2 controls iron homeostasis in haemochromatosis and thalassaemia via Bmp6 and hepcidin. 2019 Nature Metabolism. May;1(5):519-531
Eddowes LA et al. Antiviral activity of bone morphogenetic proteins and activins. Nature Microbiology. 2019 Feb;4(2):339-351.
Pasricha SR et al. Reducing anaemia in low income countries: control of infection is essential. 2018 BMJ 362:k3165.
Arezes J et al. Erythroferrone inhibits the induction of hepcidin by BMP6. 2018 Blood Oct 4;132(14):1473-1477
Pasricha SR et al. Expression of the iron hormone hepcidin distinguishes different types of anemia in African children. 2014 Sci Transl Med 6:235re233
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