Stewart and Pitt Research Groups
ajs21 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.
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.
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”.
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 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.
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.
Dr Alan Stewart and BHF-sponsored PhD student, Jordan Marsh attended the British Heart Foundation Annual Parliamentary Reception on 5th Feb 2020. The event at the parliament each year, celebrates and raises awareness of great the work carried out by the charity. The event was sponsored by Alex Cole-Hamilton, MSP and featured talks by BHF UK’s Young Volunteer of the Year, Mohamad Najjar; newly appointed Head of BHF Scotland, James Jopling; and the Minister for Public Health, Sport and Wellbeing, Joe Fitzpatrick MSP.
On the 5th December the Metal Ions in Medicine Group held their inaugural away day in the Gateway Building. On the day there were talks from post-doctoral researchers, PhD students, MSc students and an undergraduate student. Research topics included:
1. The role of zinc in cardiac muscle contraction
2. Fetal and adult circulatory zinc transport
3. The role of cobalt in ALVAL (aseptic lymphocyte-dominated vasculitis-associated lesion)
4. Characterisation of mutations in ATP2C2, a calcium/manganese transporter implicated in dyslexia
5. Biomarker discovery in esophageal adenocarcinoma
Sam and Alan would like to thank all the attendees/speakers for making the day so much fun and also to Dr Juan Varela (School of Biology) for coming along to support!
Dr Alan Stewart and Dr Sam Pitt have just been awarded a BHF PhD studentship grant of £108k for a project entitled “Role of plasma fatty acid and zinc dynamics in platelet functioning: Implications for pathological clotting“.
Zinc is an essential micronutrient that is required for many biological processes including control of coagulation. When platelets become activated they release zinc, which in turn binds to plasma proteins and cell surface receptors to regulate clotting. Currently we do not understand how zinc gets into platelets, how it is stored or how these processes may be altered in diseases associated with abnormal clotting. Elevated plasma free fatty acid (FFA) levels are associated with conditions such as cancer, obesity and diabetes, which also increase the risk of developing thrombotic blood clots. Our studies suggest that high levels of FFAs disrupt zinc handling in the blood potentially leading to thrombotic complications.
The specific aims of this project are to:
1. Examine zinc storage, compartmentalisation and flux in platelets.
2. Identify the zinc homeostatic machinery in platelets.
3. Examine the effects of FFA-mediated dysregulation of plasma zinc on platelet functioning.
We are looking for enthusiastic candidates who hold a first or upper-second class degree (and/or an MSc/MRes degree) in Molecular or Cellular Biology, Biochemistry, Chemistry or a related subject from a recognised academic institution. Applicants with some degree of laboratory research experience are particularly encouraged to apply. To apply, please visit the University of St Andrews website and download the PhD application form. Full details on how to apply are given here: http://www.st-andrews.ac.uk/study/pg/apply/research/
Dr Alan Stewart and Dr Swati Arya would like to thank the organisers of ICAP2019 for an excellent meeting in Lisbon. Alan presented our work on drusen proteomics using SWATH-MS in an invited talk entitled ‘Hydroxyapatite interactome in Age-related Macular Degeneration’. Whilst Swati scooped a poster prize with her poster entitled “Quantitative proteomic changes in LPS-activated monocyte-derived dendritic cells”.