ajs21

Cobalt-albumin manuscript accepted for publication in Chemical Science.

by

PhD student, Dongmei Wu (from the Stewart group) has had a joint first author paper focussed on serum albumin interaction with Co2+ , accepted for publication in the RSC journal, Chemical Science. The work was a collaboration between several groups, including that of Prof. Wladek Minor from the Univeristy of Virginia (who is joint lead author with Dr Stewart) and Prof. Claudia Blindauer from the University of Warwick.

Serum albumin-Co2+ interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin-Co2+ interactions was required. In the paper, the first crystallographic structures of human serum albumin (HSA; three structures) and equine serum albumin (ESA; one structure) in complex with Co2+ are presented. Amongst a total of sixteen sites bearing a cobalt ion across the structures, two locations were prominent, and they relate to metal-binding sites A and B. Site-directed mutagenesis and isothermal titration calorimetry (ITC) were employed to characterise sites on HSA. The presence of bound myristate (C14:0) in the HSA crystal structures provided insight into the fatty acid-mediated structural changes that diminish the affinity of the protein toward Co2+.

Together, these data provide further support for the idea that ischemia-modified albumin corresponds to albumin with excessive fatty-acid loading.  Collectively, our findings provide a comprehensive understanding of the molecular underpinnings governing Co2+ binding to serum albumin.

 

International Conference of Trace Elements and Minerals, Aachen, Germany.

by

Between the  5th-10th June seven members of the Metal Ions in Medicine Group were in Aachen, Germany to present their work at the International Conference of Trace Elements and Minerals. Dr Alan Stewart organised and chaired a session on Zinc in Cardiovascular Disease and gave a talk on aberrant plasma zinc handling in type 2 diabetes. Dr Samantha Pitt and Dr Amy Dorward gave Invited Talks each focussed on the role of zinc in heart failure. Jordan March gave an Oral Presentation on the role of zinc in platelets, while Stephen Hierons, Dongmei Wu and Spencer Regan-Smith gave poster presentations based on their research. The group would like to thank the organisers of the conference, particularly Prof. Lothar Rink for what was an exciting meeting held in a beautiful and historically-important city.

7th International Caparica Conference on Analytical Proteomics (ICAP)

by

On the 14th July Dr Alan Stewart gave an online invited talk at the 7th International Caparica Conference on Analytical Proteomics (ICAP), 2021 held in Lisbon, Portugal. The talk was entitled “Plasma fatty acid levels control circulatory zinc speciation: Relevance to pro-coagulatory disorders from speciomic and lipidomic studies”. He would like to thank the organisers, especially Prof Capelo for (as always!) a really exciting and engaging meeting.

UKRI-BBSRC/FAPESP Grant Award to Alan Stewart: A “speciomic” toolkit to investigate fatty acid-mediated changes in plasma zinc speciation and their physiological effects

by

Dr Alan Stewart has been awarded £783,100 from the BBSRC to fund a new bilateral project entitled “A “speciomic” toolkit to investigate fatty acid-mediated changes in plasma zinc speciation and their physiological effects”. The work will be a collaboration between researchers at the Universities of St Andrews, Warwick in the UK and Campinas in Brazil. The project, which Dr Stewart will lead, has been awarded additional funding from FAPESP (The São Paulo Research Foundation) to support the work in Brazil. As part of this study, state-of-the-art and bespoke analytical methods will be employed to understand the (re)distribution of zinc within plasma in the presence of high concentrations of fatty acids, mirroring conditions observed in disease states. The impact of this dynamic on physiological processes including insulin signalling and cellular zinc uptake will also be examined. Prof Claudia Blindauer will oversee work at the University of Warwick and Profs Marco Arruda and Carlos Ramos the research at University of Campinas.

British Heart Foundation – Lunch and Learn Talk

by

On the 15th June 2021, Dr Alan Stewart gave a Lunch and Learn talk for the British Heart Foundation based upon his research.

The talk was entitled “Could zinc be the key to new diabetes treatments?” and featured a small quiz. The audience was made up of fundraisers and other BHF staff based throughout the UK.

Fatty acids influence blood clotting through modulation of plasma zinc – new publication in Chemical Science

by

The Metal Ions in Medicine group have just published new data that may shed light on how fats in your blood could affect your health. The paper entitled “Albumin-mediated alteration of plasma zinc speciation by fatty acids modulates blood clotting in type-2 diabetes” has just been accepted for publication in the high impact journal, Chemical Science. In this study, it was found that free fatty acids  influence certain blood clotting characteristics including parameters relating to fibrin clot formation as well as platelet aggregation. It was found that the mechanism of action most likely involves reduction of zinc binding to the protein, serum albumin (the main zinc and fatty acid carrier protein in the blood) and a consequent increase in binding of zinc to proteins that regulate clot formation. The study suggests that this mechanism may contribute to pathogenic clot formation, which is more frequently observed in individuals with disease states marked by elevated plasma fatty acid levels, such as type-2 diabetes, obesity and fatty liver disease.

BioMetals 2020 Meeting

by

Dr Alan Stewart would like to thank Dr Isabelle Michaud-Soret and all the other organisers of the BioMetals 2020 Meeting which was held between the 6th -10th July 2020. The meeting was originally meant to take place in Grenoble, France but was switched to an online meeting due to the ongoing Covid-19 Pandemic. The meeting was well attended – with over 150 delegates from all over the world. Alan gave a talk on his group’s work entitled “Metal ion dyshomeostasis and coagulatory defects in type-1 and type-2 diabetes”.

Head of BHF Scotland visits St Andrews

by
James Joplin (back row, 3rd from the left) with researchers from the Stewart, Pitt and Varela research groups

On the 27th February James Joplin, the new Head of BHF Scotland visited the University of St Andrews to see the cutting edge medical and biomedical research carried out at the university. During the visit he met a number of key staff, including Prof Frank Sullivan (Director of Research) and Prof Colin McCowan (Head of Population and Behavioural Science Division). Within the School of Medicine he visited the BHF-funded Stewart, Pitt and Varela labs and met early career researchers from their respective groups. James was also given a tour of the research facilities within the Biomedical Sciences Research Complex and new Willie Russell Laboratories by Prof Terry Smith (Director of the BSRC).

Alan Stewart to be elected as Fellow of the Royal Society of Biology (FRSB)

by

Alan Stewart is to be elected as a Fellow of the Royal Society of Biology (FRSB) in April.

The Royal Society of Biology is a single unified voice for biology in the UK. The Society’s main aims are to: advise Government and influence policy; advance education and professional development; support its members, and engage and encourage the public interest in the life sciences.

The Society represents a diverse membership of individuals, learned societies and other organisations. Individual members include practising scientists, students at all levels, professionals in academia, industry and education, and non-professionals with an interest in biology.

For election as a Fellow an individual needs to have made a prominent contribution to the advancement of the biological sciences, and gained no less than five years’ experience in a position of senior responsibility.

BHF Grant Award – Plasma non-esterified fatty acids and fibrin clot formation in obesity

by

Dr Alan Stewart and Prof Ramzi Ajjan (University of Leeds) have just been awarded a BHF PhD studentship grant of £108k for a project entitled “Plasma non-esterified fatty acids and fibrin clot formation in obesity – a relationship forged in zinc?“. The grant will provide funding for Stephen Hierons.

Zn2+ is an essential regulator of coagulation and its availability in plasma is fine-tuned through buffering by human serum albumin (HSA). Non-esterified fatty acids (NEFAs) transported by HSA reduce its ability to bind/buffer Zn2+. It is thought that this occurs through binding to HSA at a particular NEFA site called FA2. This dynamic is important as plasma NEFA levels are elevated in type-2 diabetes mellitus (T2DM), obesity and other disorders that associate with an increased risk of developing thrombotic complications. Through our previous work we found that only certain plasma NEFAs are elevated in T2DM/obese subjects (compared to leaner controls without diabetes) and their levels correlate with fibrin clot parameters.

Here we will identify the role of the FA2 site in mediating Zn2+-mishandling by HSA and will assess the degree to which individual NEFAs enhance Zn2+-dependent effects on fibrin clot formation and lysis. Finally we will examine whether bariatric surgery, which is known to lower plasma NEFA concentrations in obese individuals (by restricting calorie intake), beneficially influences fibrin clot formation and lysis in obese individuals. Collectively, the work will provide essential information relating to the interplay between plasma NEFAs and a key coagulatory pathway in obesity.

 

Cookie preferences