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  Iron and Immunity: studying how iron and anaemia influence immunity and infectious diseases


   Radcliffe Department of Medicine

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  Prof A Drakesmith, Prof S Draper  No more applications being accepted  Self-Funded PhD Students Only

About the Project

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. Through collaborators in Europe, the US, Africa and Sri Lanka we have made significant contributions to how hepcidin and iron are controlled in health and disease, including anaemia, iron deficiency, HIV, HCV and typhoid fever. We utilise experimental models of key diseases, including malaria, to manipulate hepcidin during infection and understand how iron affects immunity and the outcome of infection.

Future work will cover three areas; 1) how iron and hepcidin control the Plasmodium life-cycle, the efficacy of anti-malarial drugs and the development and resolution of malarial anaemia; 2) how iron availability influences adaptive immunity, in terms of a) how iron is trafficked within lymph nodes and the spleen; 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, and immunotherapy of cancer; and 3) using our knowledge of the regulation and action of hepcidin to improve treatment of a) anaemia in the developing world, and in pregnancy and pre- and post-operative patients in UK setting, and b) iron overloading disorders including thalassaemia and haemochromatosis.

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.

As well as the specific training detailed above, students will have access to high-quality training in scientific and generic skills, as well as 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.


Funding Notes

Our main deadline for applications for funded places has now passed. Supervisors may still be able to consider applications from students who have alternative means of funding (for example, charitable funding, clinical fellows or applicants with funding from a foreign government or equivalent). Prospective applicants are strongly advised to contact their prospective supervisor in advance of making an application.

Please note that any applications received after the main funding deadline will not be assessed until all applications that were received by the deadline have been processed. This may affect supervisor availability.

References

Arezes J et al, Erythroferrone inhibits the induction of hepcidin by BMP6. Blood Oct 4;132(14):1473-1477

Pasricha SR et al, Reducing anaemia in low income countries: control of infection is essential. BMJ 2018 362:k3165.

Pasricha SR et al, Hepcidin is regulated by promoter-associated histone acetylation and HDAC3. Nat Commun. 2017 Sep 1;8(1):403

Armitage AE et al, Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections. PNAS 2018. 111:12187-12192

Pasricha SR et al, Expression of the iron hormone hepcidin distinguishes different types of anemia in African children. Sci Transl Med 2014. 6:235re233.

Drakesmith H & Prentice AM, Hepcidin and the iron-infection axis. Science 2012. Nov 9;338(6108):768-72.

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