A research grant of £110,951 has been awarded to Dr Alan Stewart and Dr Imre Lengyel (UCL Institute of Ophthalmology) from Fight for Sight to carry out a new 2-year study entitled “Identifying the hydroxyapatite interactome: clarifying the involvement of serum proteins in the formation of sub-retinal pigment epithelial (RPE) deposits”. A major feature of the ageing retina is the thickening of Bruch’s membrane and the formation of sub-retinal pigment epithelial (RPE) deposits that can block metabolic exchange between the choroidal blood circulation and the retina leading to sensory retinal degeneration and eventually to age-related macular degeneration (AMD), a major cause of visual impairment and blindess in older adults (>50 years). Recently, Thompson et al. reported the existence of small (0.5-20 μm diameter) protein-binding hydroxyapatite (HAP) spherules within sub-RPE deposits isolated from AMD-affected individuals (see link). This suggests that the spherules may provide nucleation sites for sub-RPE deposit formation, where the initiation, growth and retention of deposits are controlled by the binding of proteins present in the sub-RPE space to the spherules. In the funded study, HAP-binding proteins in the plasma of genotyped late-stage AMD patients will be isolated and quantitatively identified and biochemically characterised.

The Physiological Society, Techniques Workshop – An Introduction to Molecular Biology, UCL, 14-17 april 2015.

Ben and Gavin found the course very informative and enjoyable. The techniques learned have already been used in the lab!

Ben and Gavin would like to thank, the Physiological Society and the course organisers specifically Caroline Pellet-Many who coordinated the whole week.

A research grant of £191,250 has been awarded to Dr Alan Stewart from the British Heart Foundation to carry out a new 3-year study entitled “Role of zinc in controlling histidine-rich glycoprotein (HRG) complex formation: Implications for the development of thrombotic complications”. This work will advance current knowledge of the structure and function of HRG, a key molecule involved in controlling coagulation, and its regulation of haemostasis in health and disease. In addition, the project will evaluate a potentially novel zinc-dependent haemopathological mechanism in diabetes patients stemming from elevated plasma FFA levels and modulation of HRG functioning. The study is a collaboration between investigators at the University of St Andrews (Dr Stewart, Dr Samantha Pitt and Prof. James Naismith) and the University of Leeds (Dr Ramzi Ajjan).

The Northwood Charitable Trust has just awarded Dr Samantha J. Pitt a small grant (£21,000) titled “Regulation of cardiac function; new mechanisms and novel ion channels”

This research will address the role of zinc signalling in regulating sarcoplasmic reticulum ion-channel function during excitation contraction coupling, and will characterise the potential detrimental role of zinc in cardiomyopathies.

Many thanks for supporting our research.

Was great meeting all of the S4 pupils from St Andrews High, Kirkcaldy, at the routes into employment STEM “speed dating” event yesterday. I hope they enjoyed it as much as I did. I wish them all the best in their future careers. – Dr Samantha J. Pitt

Dr Samantha Pitt and Dr Alan Stewart would like to thank the British Heart Foundation for supporting their research titled “Understanding new mechanisms of cardiac ryanodine receptor regulation by zinc”. These funds will support Gavin Robertson during his PhD research.

Gavin starts his PhD today!

Histidine-rich glycoprotein (HRG) is a plasma protein that regulates a number of biological processes in the blood including coagulation, through its ability to bind and neutralize heparins. HRG contains a distinctive histidine-rich region that associates with zinc ions (Zn²⁺) to stimulate HRG-heparin complex formation. Under normal conditions the majority of Zn²⁺ in plasma associates with serum albumin. However, clinically high levels of free fatty acid (FFA) allosterically disrupt the major Zn²⁺-binding site on serum albumin and are associated with an increased risk of thrombotic complications. The Stewart group report in the Journal of Thrombosis and Haemostasis that increased levels of circulatory fatty acids are likely to increase the proportion of plasma Zn²⁺ associated with HRG. In this study the Zn²⁺-binding properties of HRG and the formation of HRG-heparin complexes in the presence of different Zn²⁺ concentrations were investigated. Furthermore, the binding of Zn²⁺ to serum albumin was examined in the presence of various concentrations of myristate by ITC. Speciation modeling of plasma Zn²⁺ based upon the data obtained from these experiments suggests that FFA-mediated displacement of Zn²⁺ from serum albumin is likely to contribute to the development of thrombotic complications in individuals with high plasma FFA levels – Full text is available online.

The first Zinc-NET workshop was held at the Institute of Ophthalmology, at University College London, 4th and the 5th of November.

There was an impressive line-up of speakers who discussed how to measure zinc and a “hands-on ” session for the participants. Dr Samantha Pitt would like to thank the organisers, tutors and speakers for a highly informative and thought provoking session.

For more info visit zinc-net: http://zinc-net.com

The Stewart and Pitt labs would like to congratulate Gavin on obtaining his MRes.

Well done Gavin you did a great job.

The calcium signalling meeting was a huge success. A very enjoyable and informative meeting.

Thanks to Prof. Sandip Patel and Dr Grant Churchill for putting together such an exciting programme.

Dr Samantha Pitt would like to thank the organisers for giving her the opportunity not only to present her work but also to chair a session for the first time!