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Age-related macular degeneration (AMD) is a common cause of site loss associated with the formation of proteinous deposits that block circulatory exchange with the retina. The factors that contribute to deposit formation are not well understood. Recently, the presence of spherular hydroxyapatite (HAP) structures within these deposits was discovered to which several AMD-associated proteins were bound. This suggests that protein binding to HAP represents a potential mechanism for the retention of proteins and thus deposit formation.

As part of a Fight for Sight-funded study, the Stewart lab set about identifying circulating plasma proteins that may contribute to deposit formation through binding to HAP using SWATH-MS proteomics. The study, in collaboration with Dr Imre Lengyel (Queen’s University Belfast) utilised blood plasma samples taken from phenotyped late-stage AMD patients (some of whom carry an “at risk” genetic variation, CFH T402H in their DNA). From a library of 242 identified HAP binding plasma proteins, significant quantitative differences in the abundance of 32 HAP-binding proteins (p<0.05) between the two homozygous groups (“normal” vs “at-risk”). The concentrations of six proteins (FHR1, FHR3, APOC4, C4A, C4B and PZP) in the HAP eluted fractions and whole plasma were further analysed using ELISA and their presence in sections from human cadaver eyes was examined using immunofluorescence.

The published article is available here.

Research from the Stewart lab into the role that certain fats may play in pathological blood clotting has been highlighted by the BHF in their “Heart Matters” magazine. A link to the article can be found here.

On the 31st of January Dr Samantha Pitt, Dr Alan Stewart, Amy Dorward, Amelie Sobczak and Gavin Robertson represented the Metal Ions in Medicine Group at the British Heart Foundation Scotland’s Annual Reception, which took place in the Scottish Parliament Building in Edinburgh. The event, attended by fundraisers, researchers and politicians, highlighted the great work of the BHF in funding cutting-edge research, informing policy and promoting public awareness of its activities. During the meeting they bumped into local MSP and leader of the Scottish Liberal Democrats, Willie Rennie. The reception was followed by a private dinner hosted by the Head of BHF Scotland, James Cant that Sam attended.

Alan Stewart is pleased to join the Editorial Board of the journal, Biometals. BioMetals, which is published in co-operation with the International Biometals Society, is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. It is a multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field.

Matrix mineralization is the process by which the skeleton forms and is maintained. Matrix vesicles (MVs) released from osteoblasts and chondrocytes serve to accumulate calcium and inorganic phosphate such that mineralization can take place. In a paper to be published in the FASEB Journal, the Stewart group (in collaboration with Prof Colin Farquharson, University of Edinburgh) propose the potential involvement of two enzymes, phospholipase A2 (PLA2) and ectonucleotide pyrophophatase/phosphodiesterase 6 (ENPP6), which may act together to generate inorganic phosphate from phosphatidylcholine in the MV membrane. Together they could produce phosphocholine, which in turn is a substrate for PHOSPHO1, an enzyme known to be essential for mineralization. The presented concept is backed up by various pieces of evidence; for example, both enzymes are expressed in mineralizing cells and it is known that phosphatidylcholine is broken down in MVs during mineralization. The paper, which will feature in a forthcoming issue, stemmed from a BSc(Hons) project that was researched by final year student, Darren Leong earlier this year.

Alan Stewart was recently in Xining, Qinghai Province, China, where he delivered seminars in two Chinese Academy of Sciences (CAS) Institutes. These included the North West Institute of Plateau Biology, where he was bestowed the honorary position of Guest Professor. This is in part due to a new collaborative award of ¥400,000 from CAS to Dr Ruitao Yu, an Associate Professor at the Institute and former Visiting Scholar in the Stewart Group. During this new project, Dr Yu will spend another 3 months in Dr Stewart’s lab to examine the serum albumin binding characteristics of medicinally relevant natural products. Also whilst in Xining, Dr Stewart delivered a Keynote Lecture at a High-End Forum focussed on medicinally-relevant natural products and their usefulness for treatment of cardiovascular disease. Dr Stewart’s trip to China was funded by the Administration of Foreign Experts of Qinghai Province.

The Leverhulme Trust have awarded a grant of £342,867 to Dr Claudia Blindauer, Dr Hugo van den Berg (both University of Warwick) and Dr Alan Stewart for a project entitled “A qualitative framework linking extracellular zinc speciation and cell uptake”.

Zinc is an essential micronutrient that participates in almost every major biological process. The health and wellbeing of humans and other mammals depends on well-regulated distribution of zinc among the tissues of the body. However, how this regulation is achieved is not fully understood. This new project will explore the hypothesis that uptake of zinc into cells is actively controlled by the zinc-binding capacity of major zinc-binding proteins in blood plasma. This will be achieved by combining biological, chemical, and mathematical methods. This exciting new project will provide crucial new information on an overlooked component of mammalian zinc homeostasis.

In June, Amélie Sobczak, PhD student with Dr Alan Stewart, attended the Basic Science Summer School in Nice organised by the European Society of Cardiology. This 5-day event was attended by around 70 PhD and MD/PhD students working in cardiovascular research and consisted of a series of lectures and discussions on the latest advances and challenges in the field as well as workshops on outreach, publishing and career building. During the meeting she presented a poster relating to her research on the regulation of coagulation by zinc, work supported by funding from BHF. She would like to thank the organisers, Jeremy Pearson, Peter Ferdinandy and Yasmine Carrasset. She would also like to thank the School of Medicine and CAPOD for funding to support this visit.

Congratulations to Gavin Robertson (PhD student) on his JSPS Scholarship. Gavin will spend two months working with Professor Hiroshi Takeshima at the University of Kyoto, Japan. Gavin’s is looking at diastolic calcium leak and the role of zinc.

On the 24th March three local MPs/MSPs, Roger Mullin (SNP), Willie Rennie (Scottish Lib Dems) and Alex Rowley (Labour), together with representatives from the British Heart Foundation were in St Andrews to hear about the cutting-edge cardiovascular research being carried out in the School of Medicine.  Dr Alan Stewart and Dr Sam Pitt as well as other researchers from the Metal Ions in Medicine Group (Dr Siavash Khazaipoul, Amelie Sobczak and Gavin Robertson) presented updates on their work.  In addition, Prof David Crossman and Dr Simon Powis were in attendance, with Prof Crossman providing an introduction to the school and an overview of how biomedical research is funded and its importance to Scotland.