Drakesmith Group: Using iron to control immune responses

About the Research 

Our lab works on how iron influences our physiology, especially immunity. Iron deficiency affects ~2 billion people, and ~2% of human genes encode iron-interacting proteins involved in a huge variety of crucial metabolic and regulatory activities (ref 1,2). We have found that iron deprivation has a powerful effect on innate and adaptive immune responses (refs 3-5). now seeking to understand the importance of iron for immunity in more detail and to leverage that information into generating new methods to control immune responses beneficially. 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. Ongoing lab projects comprise basic and translational directions, as detailed below, and the student will be able to choose the direction they wish to follow.

For basic science, we do not know how regulation of cellular iron uptake and storage integrates with larger control of metabolism and biochemistry – in essence, how does iron control cell identity, differentiation, and fate. We will examine this fundamental question in lymphocytes and other immune cell types during immune responses and against a background of iron deficiency, and track changes in cell behaviour through ‘omics approaches, high-dimensional phenotyping and functional assays.

We will also use our ability to manipulate iron trafficking to control immune responses for therapeutic purposes. We will use genetic and pharmacological tools to modulate supply of iron to different cell types and test the effect of such interventions in contexts of transplantation, graft-versus-host-disease, autoimmunity and anti-tumour immunity. We will collaborate with neighbouring labs in Oxford to combine our iron-oriented expertise with models of immunopathology in order to generate a synergistic approach that moves basic science concepts to pre-clinical applications.

We lead ongoing clinical trials testing how nutritional iron influences immune responses to vaccines in parallel with its effects on anaemia. These trials are generating a rich data stream that has revealed unexpected effects of iron on haematopoiesis and gastroenterological processes. Using a new mass-spectroscopy method developed with Earth Sciences, we can quantify atomic iron in single cells before and after nutritional iron and relate differences in cellular iron content to cell function. We are following up these findings mechanistically and there are many opportunities to collaborate widely in the WIMM and in Oxford in order to pursue this translational work.

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. Students will employ single-cell ‘omics and gain experience of integrating complex datasets to find mechanistic drivers of important physiological processes.

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.

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.

Additional Supervisors 

Publications