A landmark collaboration of neuroscientists has secured major further funding ($6 million) from the Aligning Science Across Parkinson’s (ASAP) initiative, in partnership with the Michael J. Fox Foundation, to continue their pioneering research in mapping neuronal circuits that become dysfunctional in Parkinson’s. The Oxford-led team will expand their recent discoveries of the molecules, cells and circuits modulating dopamine pathways to develop insights for understanding and treating Parkinson’s.
The team, led by Professor Stephanie Cragg at DPAG in the University of Oxford, has been funded by the Michael J. Fox Foundation for Parkinson’s research through the ASAP initiative since 2021. ASAP’s mission is to accelerate discovery for Parkinson’s disease through collaboration, data sharing, and resource generation. ASAP empowers researchers to push the boundaries of collaborative research and open science through sharing of data, tools, protocols, code and manuscripts by the time of publication.
Team Cragg is part of ASAP’s Collaborative Research Network (CRN), an international, multidisciplinary, and multi-institutional network of collaborating investigators who are working to address high-priority research questions. The team is building new understanding of the neuromodulators that sculpt neural signalling by dopamine and acetylcholine and how a balance between the two becomes dysregulated in Parkinson’s, resulting in problems with movement.
Together, the team of scientists from the laboratories of Stephanie Cragg, Richard Wade-Martins and Peter Magill at Oxford, Mark Howe at Boston University and Dinos Meletis at the Karolinska Institutet, with additional collaborations from Yulong Li at Peking University and Michael Lin at Stanford University, has already made several key breakthroughs. They have generated the largest single-cell dataset of gene expression in the aged mouse brain known to date (Kilfeather et al., 2024), available as an open access resource (https://spatialbrain.org).
At the circuit level they have uncovered that astrocytes – non-neuronal cells previously thought of as support cells – play an unexpected role in modulating dopamine and acetylcholine interactions (Stedenhouder et al., 2024 Nature Commun). The team has also developed an innovative multifiber array photometric technique for simultaneous recording of neurotransmitter signals across the entire striatum ( Vu et al., 2024 Neuron). These new datasets, tools and findings led the team to identify new research directions critical to furthering our understanding how dopamine and acetylcholine are regulated and lead to movement impairments, which the team will now explore with this new award.