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Iron Biology


Project Description

We study how iron and anaemia influence immunity and infectious diseases. Our research inspires therapies that control iron physiology to improve immunity, combat infections and treat disorders of iron metabolism. We work across the disciplines of immunology, haematology and global health, utilising in vitro, in vivo and human studies, and collaborate extensively to translate our mechanistic discoveries into clinically relevant progress.

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 the infection.

The hormone hepcidin controls the amount and distribution of iron in the body; expression of hepcidin is controlled by a combination of iron concentrations 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 and typhoid fever. We utilise experimental models of key diseases, including malaria and tumour models, and manipulate hepcidin to test how controlling iron homeostasis influences 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.

Funding Notes

Funding for this project is available to scientists through the RDM Scholars Programme, which offers funding to outstanding candidates from any country. Successful candidates will have all tuition and college fees paid and will receive a stipend of £18,000 per annum.
For October 2020 entry, the application deadline is 10th January 2020 at 12 noon (midday).
Please visit our website for more information on how to apply.

References

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

Armitage AE et al. Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections. 2014 Proc Natl Acad Sci U S A 111:12187-12192.

How good is research at University of Oxford in Clinical Medicine?

FTE Category A staff submitted: 238.51

Research output data provided by the Research Excellence Framework (REF)

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