Tag Archives: Oxford

Nobel Prize in Physiology or Medicine- Oxygen takes the stage….might iron follow?

Sir Peter Ratcliffe (Oxford University) has recently been announced as this year’s winner of the Nobel Prize in Physiology or Medicine alongside William Kaelin, Jr (Harvard University) and Gregg Semenza (Johns Hopkins University). 

This prize was awarded for seminal work describing the mechanisms of oxygen sensing and control. The discovery centers on hypoxia-inducible factors (HIFs), a family of transcription factors that orchestrate cellular responses to hypoxia, thereby triggering metabolic, angiogenic and cell-cycle adaptations. In the wider physiological context, HIFs orchestrate erythropoietic and cardiopulmonary responses to hypoxia. 

Nobel Prize Medicine 2019

Under normoxic conditions, these HIF proteins are constantly produced then targeted for proteolytic degradation by the action of prolyl hydroxylases (PHDs).  These enzymes act as oxygen sensors owing to their requirement for oxygen as a substrate. Sir Ratcliffe’s laboratory helped uncover the role of these enzymes and identified the sites at which HIFs are hydroxylated (1 , 2).

Beyond enhancing our understanding of basic homeostatic control, these discoveries have also had far-reaching translational applications, most notably that of inhibiting PHDs for the treatment of anaemia.

The interplay between oxygen and iron homeostasis has long been recognised. Sir Ratcliffe himself once declared that “HIF may as well be called iron deficiency-inducible factor”. Indeed, the PHDs that regulate HIF stability require iron as a co-factor. This is reflected in the pathophysiological manifestations of iron deficiency, that often mimic the body’s response to hypoxia, e.g. pulmonary arterial hypertension. Another important aspect of this interplay is the control of renal HIF2 by Iron Regulatory Proteins (IRPs), a mechanism that is thought to couple erythropoiesis to iron availability. 

For those reasons, this Nobel prize is good news for those of us interested in iron. Over the coming years, we are likely to learn of further intersections between iron and oxygen homeostasis. The challenge will be to capitalise on these, so that iron-altering therapies could be harnessed to treat disorders of hypoxic signalling and vice versa. Another challenge for us in the iron community will be to raise the profile of iron research even further with a Nobel prize of our very own! 

We are extremely pleased to announce that Sir Ratcliffe will be the keynote speaker at the upcoming European Iron Club meeting in Oxford, 2-5 September 2020. (EIC2020)

Contributed by Prof Samira Lakhal-Littleton, Department of Physiology, Anatomy & Genetics
University of Oxford

Post-doctoral Fellow – University of Oxford

A two-year post-doctoral research fellow position is available in the Drakesmith lab at the Weatherall Institute of Molecular Medicine, University of Oxford.

https://www.rdm.ox.ac.uk/people/alexander-drakesmith

With the support of an unrestricted grant from the pharmaceutical industry, the University of Oxford has driven the development of HIRO (Human Iron Research in Oxford), a cross-divisional initiative serving to link clinicians and scientists with an interest in iron research across the Oxford campuses; HIRO is led by Dr John Ryan and Prof Hal Drakesmith. Reporting to the Principal Investigator and the HIRO steering committee, the post holder will be the HIRO Fellow, a member of a research group with responsibility for carrying out studies on human-focussed translational iron research for patient benefit. The Drakesmith group is sited within the MRC Human Immunology Unit at the Weatherall Institute of Molecular Medicine. We have a strong track record in the field of iron metabolism with a specific interest in how iron trafficking interacts with infection, inflammation, immunology and anaemia. This specific project will build on published and unpublished ongoing studies relating to how iron availability controls inflammation and immunity and will involve interaction with academic groups within and beyond Oxford. The post holder provides guidance to junior members of the research group including research assistants, PhD students, and/or project volunteers. The post-holder will also work to connect the other HIRO-funded projects within the University of Oxford.

Please find further details of the position and how to apply here.