Drakesmith Group - Iron Biology
- Hal Drakesmith
About the Research
Iron deficiency affects ~2 billion people, and ~2% of human genes encode iron-interacting proteins involved in processes including mitochondrial metabolism, epigenetic regulation and DNA synthesis. 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 clinical trials and medically 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 infections.
Future work in the lab will comprise basic and translational directions and the student is able to choose the direction they wish to follow. For basic work, although we understand how iron is regulated in cells, we do not know how this process integrates with larger control of metabolism, and so cell fate, differentiation and function. We will examine this fundamental question of how iron interacts with metabolic reprogramming in lymphocytes and other immune cell types during immune responses and against a background of iron deficiency. We will also use our ability to manipulate iron trafficking to control immune responses for therapeutic purposes. This translational work will employ a variety of genetic and pharmacological tools to modulate supply of iron to immune cells and test the effect of such interventions in contexts of pathological immune attack, for example in transplantation, graft-versus-host-disease and autoimmunity. We will collaborate with neighbouring labs in Oxford to combine our iron-oriented expertise with models of immunopathology (including humanised mice) in order to generate a synergistic approach that moves basic science concepts to pre-clinical applications.
Additional supervision may be provided by Oliver Bannard, Fadi Issa and Adam Wilkinson.
Please see the Weatherall Institute for Molecular Medicine (WIMM) for information about applications for a DPhil in Medical Sciences with groups based in the WIMM.
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.
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.
Frost JN, et al. Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection. Med. 2021 Feb 12;2(2):164-179.e12. doi: 10.1016/j.medj.2020.10.004.
Teh MR et al, Analysis of Iron and Iron-Interacting Protein Dynamics During T-Cell Activation. Front Immunol. 2021 Aug 12;12:714613. doi: 10.3389/fimmu.2021.714613
Frost JN, et al. Plasma iron controls neutrophil production and function. Sci Adv. 2022 Oct 7;8(40):eabq5384. doi: 10.1126/sciadv.abq5384
Drakesmith H, et al. Vaccine efficacy and iron deficiency: an intertwined pair? Lancet Haematol. 2021 Sep;8(9):e666-e669. doi: 10.1016/S2352-3026(21)00201-5.
Lim PJ, et al. Nrf2 controls iron homeostasis in haemochromatosis and thalassaemia via Bmp6 and hepcidin. Nat Metab. 2019 May;1(5):519-531. doi: 10.1038/s42255-019-0063-6
Drakesmith H & Prentice AM. Hepcidin and the iron-infection axis. Science. 2012 Nov 9;338(6108):768-72. doi: 10.1126/science.1224577.