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Iron, immunity, anaemia, and infection

Drakesmith group iron and immunity

 

About the Research

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.

 

Training Opportunities

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 WIMM 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 MRC 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 MRC 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.

 

Publications

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.


Supervisors

Other potential supervisors

Prof Simon Draper
Nuffield Department of Medicine