Gordon Conference – Cell biology of Metals 2015

Cell Biology of Metals, Gordon Research Conference, 26-31 July 2015

Dr Samantha Pitt would like to thank Profs Amy Palmer and Dennis Thiele for putting together such an exciting programme.

Samantha Pitt presented her work looking at how “Zinc Modulates Cardiac Ryanodine Receptor Function Resulting to Altered Intracellular Ca(II)-Dynamics”

GRC 2015_Pitt


Travel Award for Dagmara to attend EMDS Meeting

Dagmara Wiatrek has been awarded £400 from the European Macrophage and Dendritic Cell Society (EMDS) to attend their annual meeting in Krakow, Poland in September. Dagmara will present part of her PhD studies at the meeting relating to zinc transporter expression in dendritic cells .

Physiology 2015

Physiology 2015, Cardiff 6-8 July, was a fantastic meeting and we would like to thank the organisers for putting together such an exciting programme.
Dr Samantha Pitt gave a talk entitled “Recombinant human TPC2 and TPC1 are both NAADP-regulated ion channels but display important functional differences”
Ben Reilly-O’Donnell presented his work on how “zinc modulates RyR2 function and may lead to “leaky” channels in heart failure”
Gavin Robertson also presented his work “Exploring a novel role for zinc in modulation of sarcoplasmic reticulum calcium release in skeletal muscle”

Intracellular zinc modulates cardiac ryanodine receptor-mediated calcium release

Cardiac excitation-contraction (EC) coupling, a process which governs contractility of the heart, depends on the controlled release of calcium ions (Ca2+) from the sarcoplasmic reticulum (SR) through specialised Ca2+-release channels called type-2 ryanodine receptors (RyR2). RyR2 plays a pivotal role as the main pathway for the release of Ca2+, driving cellular contraction. Consequently, dysfunction in the release of Ca2+ through these channels and the modulatory influences which control RyR2 function have been identified as contributory to the pathophysiology of heart failure and fatal cardiac arrhythmias.

Very recently a link between elevated levels of intracellular zinc and heart disease has been highlighted, but very little is understood regarding the role of zinc in the heart. In this latest publication in The Journal of Biological Chemistry the Pitt group show that Zn2+ is a high affinity regulator of RyR2 displaying three modes of operation. Picomolar free Zn2+ concentrations potentiate RyR2 responses but channel activation is still dependent on the presence of cytosolic Ca2+. At concentrations of free Zn2+ >1 nM, Zn2+ is the main activating ligand and the dependency on Ca2+ is removed. Zn2+ is therefore a higher affinity activator of RyR2 than Ca2+. This work suggest that RyR2-mediated Ca2+-homeostasis is intimately related to intracellular Zn2+ levels providing a mechanistic explanation linking altered Zn2+ homeostasis to cardiac RyR2 function.The data presented represents a shift in our understanding of how RyR2 is activated during EC coupling and indicates that channel dysregulation, through aberrant Zn2+ homeostasis, is likely to play a fundamental role in the generation of heart failure and other arrhythmic diseases. Full text is available online.


Fight for Sight Grant Award

A researffs_logo_blue_croppedch 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.

An Introduction to Molecular Biology – The Physiological Society

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!Gel Phys Soc WS

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

Ben and Gavin Phys Soc WS

British Heart Foundation Grant Award

BHF logoA 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).