UKRI-BBSRC Grant Awarded to Samantha Pitt – High-resolution structure, function and anti-viral inhibition of the SARS-CoV-2 E protein ion channel

Dr Samantha Pitt and partners from University of Dundee (Prof Ulrich Zachariae) and Trinity College Dublin (Prof Martin Caffrey), have recently been awarded a UKRI-BBSRC grant to address problems related to COVID-19. Employing an interdisciplinary approach, the team will use structure-based drug design to accelerate the discovery of drugs to target SARS-CoV2 by enabling focused, rational approaches to design and repurposing. The project aims to i) solve high-resolution crystal-structures of CoV2E (ii) apply computational electrophysiology and in silico screens including cheminformatics/machine learning approaches to identify CoV2E inhibitors from libraries of commercially available and repurposing drugs, and (iii) perform lead validation and further development of inhibitors by electrophysiology and crystallography.



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

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 Samantha Pitt becomes a commitee member of the Scottish Cardiovascular Forum

Dr Samantha Pitt has been invited to become a committee member of the Scottish Cardiovascular Forum to represent the University of St Andrews. The Scottish Cardiovascular Forum was launched in October 1997, with the aim of fostering integration, encouraging collaboration and assisting in the dissemination of information among basic science and clinical cardiovascular researchers in Scotland and further afield.

BioMetals 2020 Meeting

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”.

Our paper in Nature Photonics is now available – Monitoring contractility in cardiac tissue with cellular resolution using biointergrated microlasers

Our latest collaborative work on microlasers as versatile contractility sensors in the heart is out.

Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers” by Marcel Schubert, Lewis Woolfson, Isla R M Barnard, Amy M Dorward, Becky Casement, Andrew Morton, Gavin B Robertson, Paul L Appleton, Gareth B Miles, Carl S Tucker, Samantha J Pitt and Malte C Gather is published in Nature Photonics and available online.

In this work we show that implanted microlasers can scan heart tissue from inside cells.  Tiny lasers were placed inside the heart where they acted as microscopic probes. With every beat of the heart, the colour of light that these lasers emit changed by a small but clearly detectable amount, thus precisely encoding the contractions of the heart cells over time.

Although the research is still in its early days, the present study proves that lasers can resolve fast dynamic processes inside individual live cells and whole hearts.

Our University press release can be found here

Head of BHF Scotland visits St Andrews

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)

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

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.


BHF Annual Parliamentary Reception 2020

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.

Metal Ions in Medicine Away Day

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!