Cardiff University (CU)
Partner description and expertise
Cardiff University is recognised in independent UK government assessments as one of Britain’s leading teaching and research-intensive universities. The Cardiff School of Biosciences is ranked in the top 10 within the UK and top 100 in the world, with world leading scientists in many fields. The Lloyd-Evans research group occupies space within the School and is mainly focused on improving our understanding and treatment of neurodegenerative lysosomal storage diseases. The Lloyd-Evans research group has all modern dedicated facilities and the laboratory is considered as being world experts on lysosomal CA2+ measurements, lysosomal cell biology and purification and targeted drug development for human diseases based on understanding pathogenic cascades.
Role in the BATCure project
CU's team consists of Dr. Emyr Lloyd-Evans, Dr. Luke J. Haslett and Dr. Helen Waller-Evans, who will be using their expertise in measuring intracellular CA2+ homeostasis and signalling and lysosomal cell biology. The research group will also be utilising their expertise in targeted drug development to determine therapeutic benefit on any phenotypes they identify. They will more specifically be utilising some of their techniques for which they are not only the world leading expert but also amongst the very few labs that actually do the techniques. For example, their preliminary data has identified that the CLN3 protein may be a lysosomal member of the TMBIM family of Ca2+ leak channels and that lysosomal Ca2+ levels are elevated in CLN3 cells. To fully explore its function the Lloyd-Evan’s laboratory will measure intra-organellar lysosomal Ca2+ levels, lysosomal Ca2+ homeostasis in response to pharmacological manipulation, lysosomal Ca2+ signalling in response to endogenous ligands and intracellular Ca2+ signalling in response to changes to lysosomal Ca2+.
In addition, they will utilise the new magnetic separation technology they have developed in conjunction with Liquids Research to purify lysosomes in order to further characterise CLN3 function as a lysosomal Ca2+ channel but in purified organelles without contamination by other membranes. This technique will allow the laboratory to do single channel recordings (an expertise of several labs at Cardiff University) to determine the 666918 BATCure – Part B 67 Ca2+ transport properties of CLN3 directly. Furthermore, they will utilise the expertise they have shown in developing therapies (miglustat and curcumin) and biomarkers (lysotracker) for NPC disease, targeted around the lysosomal Ca2+ phenotypes they identified, and will adapt this strategy for CLN3. Finally, they will utilise the unique tools that the laboratory has expertise with to help in the characterisation of the function of the lysosomal CLN7 protein, another potential ion transporter.
