The Manchester Metropolitan University (MMU)


Partner description and expertise

The Manchester Metropolitan University (MMU) is the largest campus-based university in the UK. Researchers are involved in international leading research in a range of areas including healthcare sciences. The recent UK Research Excellence Framework assessment ranked 60% of MMU’s research output as of world leading or internationally excellent quality and health/healthcare sciences research was ranked 12th in the UK for overall research power. MMU has experience of participating in, and managing a range of European funded research projects including a number supported by Horizon 2020 and previous Framework Programmes. MMU enjoys close links with local NHS Trusts including Central Manchester University Hospitals NHS Foundation Trust, (CMFT) and local Clinical Research Networks. Along with University of Manchester and NHS Trusts (including CMFT), MMU is part of the Manchester Academy for Healthcare Science Education (MAHSE), which holds a national contract for a Doctor of Clinical Science programme for Healthcare Scientists. It also holds a contract to provide professional training for NHS healthcare scientists. Prof McKay and his group are based in the Centre for Healthcare Research within the School of Healthcare Sciences in the Faculty of Science & Engineering. The Centre undertakes translational research to understand biological systems in disease, sensing and detecting by-products of biological systems in disease, sensing and detecting by-products of disease and contemporary challenges, including ageing and development of new technologies for personalised medicine.

Role in the BATCure project

MMU will develop stem cell based models of Batten’s disease for use in four further work packages. MMU will generate new induced pluripotent stem cell (iPSc) lines from CLN3 mouse models and patients with CLN3, CLN6 and CLN7 as well as reverting the known and characterised debilitating mutations in these genes to wild-type to act as isogenic controls using CRISPR/Cas9 genome editing. Human and mouse iPSc lines will be generated using integration-free episomal plasmids, validated using a comprehensive established set of criteria including markers of pluripotency, demethylation of endogenous pluripotency gene promoters and differentiation potential. Both 2D and 3D neural cultures derived from these lines will be used for metabolic studies in WP2 and drug screening in WP5. They have established 2D targeted differentiation cultures to astrocytes and neurons, which can be proportionately mixed to provide relevant models for WP2 and WP5. Equally, they have developed cultures to generate complex, self-organising CNS organoids for use in WP2 and gene therapy evaluations in WP8. In parallel, they will generate CLN3, CLN6 and CLN7 genome edited human embryonic stem cell (hESc) lines from a single parental line Shef3. They already have comprehensive data showing that Shef hESc are capable of differentiating to all neuronal and astrocyte sub-types. These lines will be employed in metabolome and drug library screening (WP3 and WP5 respectively) rather than patient-derived iPSc so that data can be normalised collectively against a single parental control and is thus comparable between CLNs. Shef3 CLN3, CLN6 and CLN7 lines will be exome sequenced to screen for off-target genome editing prior to engaging in large scale screens.

Prof. Tristan McKay is Professor in Stem Cell Research. He leads a group of researchers investigating the signalling pathways underlying cellular reprogramming during differentiation and de-differentiation. His group has established strong national and international collaborations in iPSc disease modelling and regenerative medicine therapies.