Cell and circuit substrates of normative and impaired motor operations

Lead Research Organisation: University of Oxford

Abstract

Nerve cells in a brain region called the basal ganglia are important for making decisions and acting on them. The basal ganglia do not work properly in Parkinson’s disease, leading to difficulties with moving.
Here, we aim to explain how nerve cells in the basal ganglia work together to support purposeful movement. We will focus our efforts on discovering when, why and how different types of nerve cell use special patterns of electrical activity, connections and chemical messengers to control behaviour. As an important part of this, we will define how changes to signalling with the chemical dopamine, as occurs in Parkinson’s, changes the ways these nerve cells interact and influence behaviour. This should help us better understand why people with Parkinson’s have difficulties with moving. These important issues cannot be tackled by studying humans alone, so we study the ways in which brain cells work in mice, which have basal ganglia similar to humans.
This research will provide important new knowledge about how cells in the basal ganglia communicate with each other in health and disease. This new knowledge will in turn put us in a stronger position to develop new therapies that are better able to manage brain activity and provide improved relief from the symptoms of Parkinson’s.

Technical Summary

The burden of disease is not borne evenly across all cell types in the brain. As such, it is imperative that the design of new strategies for treating disease progression and symptoms is informed by a mature knowledge of how different cell types fulfil their specialised roles to govern behaviour. The overall aim of this new Programme is to deliver high-resolution mechanistic explanations of the brain cell and circuit substrates of normative movement as well as impaired Parkinsonian behaviour. Focusing on the ‘motor domains’ of basal ganglia circuits in the brain, we will harness cutting-edge technologies for monitoring and manipulating neurons in vivo to provide essential new insights into how the activities and interactions of identified cell types are configured in their host circuits according to the temporal dynamics of dopaminergic signalling as well as action. As a key corollary, we will define how dopaminergic signalling arises in the basal ganglia and to what extent it is altered by factors of high relevance for early and sustained manifestations of Parkinson’s disease. We will also define how profound deficits in dopamine release, as occur in advanced Parkinsonism, impact on the cell-type-dependent encoding of behaviour in these circuits. To achieve our specific research objectives, we will couple novel and advanced analytical techniques with experimental interventions designed to probe causal interactions between specified circuit elements with high spatiotemporal precision. Our experiments will centre on the use of wild type and genetically-altered mice, with intact or comprised midbrain dopaminergic systems, the readouts from which will straddle multiple levels of function including molecular/genetic, structural, electrophysiological, neurochemical and behavioural. In capitalising on the new understanding of the activity dynamics of identified neurons gained here, we will also exploit specified cell types as novel points of entry for spatiotemporally-patterned interventions designed to not only dissect circuit function but also to correct circuit dysfunction and related behavioural impairments in advanced Parkinsonism.

Publications

10 25 50
 
Title Banbury Museum & Gallery exhibition 
Description Some of the Unit's microscopic images, illuminating in beautiful detail the circuits and cells of the mammalian brain, were on public display as part of an exhibition held at the Banbury Museum & Gallery. The exhibition, entitled "Your Amazing Brain: A User's Guide", ran from 12th February to 5th June 2022 and was an interactive, family-friendly experience offering the public an opportunity to journey inside the brain and discover more about what makes the brain so special. The Unit's images, formed the core of a gallery piece "Zoom into your brain" that showcased, at increasing magnification, the organisation of the brain into regions, different types of neurons, and specialised structures such as axons, dendrites, and synaptic connections. Two researchers from my Group provided spectacular shots taken with the Unit's microscopes. One of my group members also led on the curation of the Unit's images for the exhibition. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2022 
Impact The feedback from the public attending the exhibit has been very positive. New collaborative relationship formed between the Unit and the Banbury Museum & Gallery. 
URL https://www.mrcbndu.ox.ac.uk/news/units-images-brain-featured-museum-exhibition
 
Description Chair, Animal Welfare and Ethical Review Body (Oxford)
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
Impact Improvements in use of animals in research at Oxford University.
URL http://www.vet.ox.ac.uk/hoadmin/ERP.html
 
Description Member of MRC Quinquennial Review Panel - Institute #1
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Member of MRC Quinquennial Review Panel - Institute #2
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Member of Neuroscience and Mental Health Board, Medical Research Council
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL https://mrc.ukri.org/about/our-structure/research-boards-panels/neurosciences-mental-health-board/
 
Description Member of Research Grants Board 20K (Biological Sciences), The Royal Society
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL https://royalsociety.org/people/peter-magill-9962/
 
Description Member of Training and Careers Oversight Group, Medical Research Council
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
URL https://www.ukri.org/about-us/mrc/how-we-are-governed/training-and-careers-group/
 
Description Member, Steering Group of Oxford-MRC Doctoral Training Partnership.
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
URL https://www.medsci.ox.ac.uk/study/graduateschool/mrcdtp
 
Description BBSRC Project Grant (Response Mode) (R.B., M.W).
Amount £689,110 (GBP)
Funding ID BB/S006338/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2020 
End 12/2022
 
Description BMS Sponsored Research Project - The emergence of Lewy pathology and its manifold sequelae in vivo
Amount £590,000 (GBP)
Organisation Bristol-Myers Squibb 
Sector Private
Country United States
Start 12/2020 
End 06/2024
 
Description MRC Networking Call - MAGNETO: Magnetic Actuators and Neural Engineering for TMS Optimisation
Amount £199,950 (GBP)
Funding ID MC_PC_21019 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2022 
End 12/2024
 
Description Mapping the modulatory landscape governing striatal dopamine signaling and its dysregulation in Parkinson's disease
Amount $8,993,237 (USD)
Funding ID ASAP-020370 
Organisation Aligning Sciences Across Parkinson's 
Sector Charity/Non Profit
Country United States
Start 11/2021 
End 10/2024
 
Description Monument Trust Discovery Award (Renewal)
Amount £5,800,000 (GBP)
Funding ID J-1403 
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2015 
End 06/2021
 
Description New Investigator Award
Amount £1,755,735 (GBP)
Funding ID 101821/Z/13/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2014 
End 03/2021
 
Description Oxford-BMS DUB Alliance
Amount £4,750,414 (GBP)
Organisation Bristol-Myers Squibb 
Sector Private
Country United States
Start 05/2021 
End 06/2023
 
Description Oxford-FORMA Therapeutics Research Alliance
Amount £7,353,619 (GBP)
Organisation FORMA Therapeutics 
Sector Private
Country United States
Start 04/2018 
End 05/2021
 
Description Parkinson's UK Project Grant
Amount £216,824 (GBP)
Funding ID G-1702 
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2018 
End 03/2021
 
Description WT Collaborative Award in Science - Compartmentalised calcium handling in dopamine neurons: importance for selective vulnerability in Parkinson's.
Amount £3,743,939 (GBP)
Funding ID 223202/Z/21/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2022 
End 04/2027
 
Title 'Mitochondria-reporting' mouse model of Parkinsonism. 
Description We have generated a new line of genetically-altered mice that facilitate interrogation of mitochondrial function in the context of genetic burden relevant to Parkinson's. These mice are unique in: (1) expressing a genetically-encoded ratiometric fluorescent reporter of mitochondria; (2) moderately over-expressing wildtype human alpha-synuclein; and (3) lacking confounding mouse genes encoding alpha-synuclein. Expression of the fluorescent reporter allows for quantitative assays of mitochondrial abundance, structure and turnover in neurons that are vulnerable in Parkinson's. Over-expression of human alpha-synuclein recapitulates a genetic burden of relevance for inherited and idiopathic Parkinson's disease (see Janezic et al. (2013) and Dodson et al. (2016) and Roberts et al. (2020) in Publications section). We have also generated the genetic controls for this new mouse line. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2021 
Provided To Others? No  
Impact We are using this new mouse line as a research tool. We have also given some mice to collaborators at Oxford. No definitive impacts yet. 
 
Title Flp-dependent constructs and viral vectors 
Description We have generated new DNA constructs and viral vectors (AAVs) harbouring Flippase (Flp)-dependent gene expression. These tools will facilitate access to and interrogation of Flp-expressing neurons in the brain. 
Type Of Material Biological samples 
Year Produced 2016 
Provided To Others? No  
Impact We are using these research tools, but no definitive impacts yet. 
 
Description Aligning Science Across Parkinson's (ASAP) Collaborative Research Network 
Organisation Aligning Sciences Across Parkinson's
Country United States 
Sector Charity/Non Profit 
PI Contribution I collaborate with 2 other Oxford groups, as well as groups at the Karolinska Institutet (Sweden) and Boston University (USA), as part of a substantial research consortium focused on mapping the modulatory landscape governing striatal dopamine signalling and its dysregulation in Parkinson's. I acted as a Co-Applicant in the bid for consortium funding. I co-lead on research efforts directed toward the electrophysiological and photometric interrogation of mouse models of Parkinson's. Our consortium is by default part of the larger Collaborative Research Network of Aligning Science Across Parkinson's, which is made of up for ca. 50 groups from around the world.
Collaborator Contribution Guide and inform our research using mouse models of Parkinson's.
Impact Oxford-Sweden-Boston consortium awarded substantial research funding (9 million USD over 3 years). See Further Funding section.
Start Year 2021
 
Description Aligning Science Across Parkinson's (ASAP) Collaborative Research Network 
Organisation Boston University
Country United States 
Sector Academic/University 
PI Contribution I collaborate with 2 other Oxford groups, as well as groups at the Karolinska Institutet (Sweden) and Boston University (USA), as part of a substantial research consortium focused on mapping the modulatory landscape governing striatal dopamine signalling and its dysregulation in Parkinson's. I acted as a Co-Applicant in the bid for consortium funding. I co-lead on research efforts directed toward the electrophysiological and photometric interrogation of mouse models of Parkinson's. Our consortium is by default part of the larger Collaborative Research Network of Aligning Science Across Parkinson's, which is made of up for ca. 50 groups from around the world.
Collaborator Contribution Guide and inform our research using mouse models of Parkinson's.
Impact Oxford-Sweden-Boston consortium awarded substantial research funding (9 million USD over 3 years). See Further Funding section.
Start Year 2021
 
Description Aligning Science Across Parkinson's (ASAP) Collaborative Research Network 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution I collaborate with 2 other Oxford groups, as well as groups at the Karolinska Institutet (Sweden) and Boston University (USA), as part of a substantial research consortium focused on mapping the modulatory landscape governing striatal dopamine signalling and its dysregulation in Parkinson's. I acted as a Co-Applicant in the bid for consortium funding. I co-lead on research efforts directed toward the electrophysiological and photometric interrogation of mouse models of Parkinson's. Our consortium is by default part of the larger Collaborative Research Network of Aligning Science Across Parkinson's, which is made of up for ca. 50 groups from around the world.
Collaborator Contribution Guide and inform our research using mouse models of Parkinson's.
Impact Oxford-Sweden-Boston consortium awarded substantial research funding (9 million USD over 3 years). See Further Funding section.
Start Year 2021
 
Description Aligning Science Across Parkinson's (ASAP) Collaborative Research Network 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution I collaborate with 2 other Oxford groups, as well as groups at the Karolinska Institutet (Sweden) and Boston University (USA), as part of a substantial research consortium focused on mapping the modulatory landscape governing striatal dopamine signalling and its dysregulation in Parkinson's. I acted as a Co-Applicant in the bid for consortium funding. I co-lead on research efforts directed toward the electrophysiological and photometric interrogation of mouse models of Parkinson's. Our consortium is by default part of the larger Collaborative Research Network of Aligning Science Across Parkinson's, which is made of up for ca. 50 groups from around the world.
Collaborator Contribution Guide and inform our research using mouse models of Parkinson's.
Impact Oxford-Sweden-Boston consortium awarded substantial research funding (9 million USD over 3 years). See Further Funding section.
Start Year 2021
 
Description Alzheimer's Research UK Oxford Drug Discovery Institute 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution I collaborate with 21 other Oxford groups, and numerous eternal parties, as part of the Alzheimer's Research UK Oxford Drug Discovery Institute. I was invited to join the Consortium, and act as a Co-Applicant in the bid for initial ARUK funding (see: http://o3di.medsci.ox.ac.uk/co-applicants ), to help drive efforts directed toward the phenotyping of whole-animal models of dementia.
Collaborator Contribution Guide and inform our work on the use of whole-animal models for drug discovery.
Impact Consortium awarded substantial research funding (more than 10 million over 5 years). Consortium research is multidisciplinary, spanning clinical and non-clinical work at the forefront of genomics/genetics, bioinformatics, pharmacology, medicinal chemistry, functional imaging etc.
Start Year 2015
 
Description Antibodies for definition of syncleinopathy in animal models. 
Organisation Aarhus University
Country Denmark 
Sector Academic/University 
PI Contribution I collaborate with researchers at Aarhus University, Denmark, to characterise the syncleinopathy emerging in our whole-animal models of neurodegenerative disease.
Collaborator Contribution Our collaborators sent us the bespoke antibodies they generated. We are using these antibodies to inform our phenotyping of our whole-animal models.
Impact New anatomical data defining patterns of syncleinopathy emerging in whole-animal models of neurodegenerative disease.
Start Year 2020
 
Description Celgene/Bristol Myers Squibb (autophagy in animal models) 
Organisation Bristol-Myers Squibb
Department Celgene
Country United States 
Sector Private 
PI Contribution I collaborate with personnel at Celgene/Bristol Myers Squibb to advance our phenotyping of whole-animal models of neurodegenerative disease, with a scientific focus on autophagy.
Collaborator Contribution Guide and inform our work on the use of whole-animal models for drug discovery.
Impact Awarded funding as Sponsored Research Project (see Further Funding section).
Start Year 2020
 
Description Defining the expression of GABA transporters in the mouse striatum 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed to design, execution and interpretation of anatomical experiments designed to define the relationship between striatal dopamine release and GABA transporter expression, thus providing new insights into the substrates controlling dopamine signalling.
Collaborator Contribution Generated voltammetric and electrophysiological data defining the effect of drugs targeting GABA transporters on striatal dopamine release, thus providing new insights into the substrates controlling dopamine signalling.
Impact Published one original research paper with collaborators in an international peer-reviewed journal (Roberts et al., 2020; see Publications section).
Start Year 2018
 
Description Lewy bodies and cell function 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution To gain new knowledge about how Lewy bodies impact on cell function in neurological disease, I collaborate with researchers who are expert in animal models of Lewy pathology. As part of this, I generate and analyse electrophysiological and anatomical data gathered using rodents (mice).
Collaborator Contribution Provision of custom-made materials for inducing Lewy body-like aggregates in rodent models, and assistance with interpretation of data from analyses of rodent brain.
Impact Awarded project grant funding from Parkinson's UK (see Further Funding section).
Start Year 2017
 
Description Lewy bodies and cell function 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution To gain new knowledge about how Lewy bodies impact on cell function in neurological disease, I collaborate with researchers who are expert in animal models of Lewy pathology. As part of this, I generate and analyse electrophysiological and anatomical data gathered using rodents (mice).
Collaborator Contribution Provision of custom-made materials for inducing Lewy body-like aggregates in rodent models, and assistance with interpretation of data from analyses of rodent brain.
Impact Awarded project grant funding from Parkinson's UK (see Further Funding section).
Start Year 2017
 
Description Lewy bodies and cell function 
Organisation University of Pennsylvania
Department Perelman School of Medicine
Country United States 
Sector Academic/University 
PI Contribution To gain new knowledge about how Lewy bodies impact on cell function in neurological disease, I collaborate with researchers who are expert in animal models of Lewy pathology. As part of this, I generate and analyse electrophysiological and anatomical data gathered using rodents (mice).
Collaborator Contribution Provision of custom-made materials for inducing Lewy body-like aggregates in rodent models, and assistance with interpretation of data from analyses of rodent brain.
Impact Awarded project grant funding from Parkinson's UK (see Further Funding section).
Start Year 2017
 
Description MRC Units/Centres Network - MAGNETO 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution The MRC Brain Network Dynamics Unit is partnering with the MRC Cognition and Brain Sciences Unit at the University of Cambridge and the MRC Centre for Neurodevelopmental Disorders at King's College London to advance the use of next-generation transcranial magnetic stimulation devices for studies of human brain function in health and disease. As part of this collaboration, the MRC Brain Network Dynamics Unit will leverage its bioengineering expertise and industry partnerships to develop devices that allow for unprecedented control over the patterns of magnetic stimuli that can be delivered to the brain. I helped to coordinate a bid for collaborative funding.
Collaborator Contribution Guide and inform the MRC Brain Network Dynamics Unit's work in the fields of on translational bioengineering and brain stimulation.
Impact We and our 2 partners have been collectively awarded a research grant to support our networking activities (200k GBP over 2 years). See Further Funding section.
Start Year 2022
 
Description MRC Units/Centres Network - MAGNETO 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution The MRC Brain Network Dynamics Unit is partnering with the MRC Cognition and Brain Sciences Unit at the University of Cambridge and the MRC Centre for Neurodevelopmental Disorders at King's College London to advance the use of next-generation transcranial magnetic stimulation devices for studies of human brain function in health and disease. As part of this collaboration, the MRC Brain Network Dynamics Unit will leverage its bioengineering expertise and industry partnerships to develop devices that allow for unprecedented control over the patterns of magnetic stimuli that can be delivered to the brain. I helped to coordinate a bid for collaborative funding.
Collaborator Contribution Guide and inform the MRC Brain Network Dynamics Unit's work in the fields of on translational bioengineering and brain stimulation.
Impact We and our 2 partners have been collectively awarded a research grant to support our networking activities (200k GBP over 2 years). See Further Funding section.
Start Year 2022
 
Description Mapping whole-brain inputs to basal ganglia neurons. 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution I collaborate with researchers at the Karolinska Institutet, Sweden, to map the whole-brain inputs to genetically-defined set of neurons in the basal ganglia.
Collaborator Contribution Our collaborators sent us the bespoke viral vector tools they generated. We are using these tools to generate quantitative data on the whole-brain inputs to genetically-defined set of neurons in the basal ganglia.
Impact Original research paper submitted for peer review and deposited on bioRxiv: https://www.biorxiv.org/content/10.1101/2020.11.26.400242v1
Start Year 2014
 
Description Oxford-BMS DUB Alliance 
Organisation Bristol-Myers Squibb
Country United States 
Sector Private 
PI Contribution I collaborate with 6 other Oxford groups, as well as with personnel at Bristol Myers Squibb (USA) and Evotec (Germany), as part of the Oxford-BMS DUB Alliance. I acted as a Co-Applicant in the bid for consortium funding. I lead on research efforts directed toward the phenotyping of whole-animal models of neurodegenerative disease.
Collaborator Contribution Guide and inform our work on the use of whole-animal models for drug discovery.
Impact Oxford groups awarded substantial research funding (4.8 million GBP over 2 years). See Further Funding section.
Start Year 2021
 
Description Oxford-BMS DUB Alliance 
Organisation Evotec
Country Germany 
Sector Private 
PI Contribution I collaborate with 6 other Oxford groups, as well as with personnel at Bristol Myers Squibb (USA) and Evotec (Germany), as part of the Oxford-BMS DUB Alliance. I acted as a Co-Applicant in the bid for consortium funding. I lead on research efforts directed toward the phenotyping of whole-animal models of neurodegenerative disease.
Collaborator Contribution Guide and inform our work on the use of whole-animal models for drug discovery.
Impact Oxford groups awarded substantial research funding (4.8 million GBP over 2 years). See Further Funding section.
Start Year 2021
 
Description Oxford-BMS DUB Alliance 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution I collaborate with 6 other Oxford groups, as well as with personnel at Bristol Myers Squibb (USA) and Evotec (Germany), as part of the Oxford-BMS DUB Alliance. I acted as a Co-Applicant in the bid for consortium funding. I lead on research efforts directed toward the phenotyping of whole-animal models of neurodegenerative disease.
Collaborator Contribution Guide and inform our work on the use of whole-animal models for drug discovery.
Impact Oxford groups awarded substantial research funding (4.8 million GBP over 2 years). See Further Funding section.
Start Year 2021
 
Description Oxford-FORMA Therapeutics Research Alliance 
Organisation FORMA Therapeutics
Country United States 
Sector Private 
PI Contribution I collaborate with 6 other Oxford groups, as well as with personnel at FORMA Therapeutics, as part of the new Oxford-FORMA Therapeutics Research Alliance. I was invited to join the Alliance, and acted as a Co-Applicant in the bid for FORMA Therapeutics funding, to help drive efforts directed toward the phenotyping of whole-animal models of neurodegenerative disease.
Collaborator Contribution Guide and inform our work on the use of whole-animal models for drug discovery.
Impact Oxford groups awarded substantial research funding ( 7.3 million GBP over 3 years).
Start Year 2018
 
Description Oxford-FORMA Therapeutics Research Alliance 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution I collaborate with 6 other Oxford groups, as well as with personnel at FORMA Therapeutics, as part of the new Oxford-FORMA Therapeutics Research Alliance. I was invited to join the Alliance, and acted as a Co-Applicant in the bid for FORMA Therapeutics funding, to help drive efforts directed toward the phenotyping of whole-animal models of neurodegenerative disease.
Collaborator Contribution Guide and inform our work on the use of whole-animal models for drug discovery.
Impact Oxford groups awarded substantial research funding ( 7.3 million GBP over 3 years).
Start Year 2018
 
Description Striatal encoding of action 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution To gain new knowledge about how the striatum encodes the costs and benefits of acting, I collaborate with researchers who are expert in the analysis of animal behaviour and the imaging of brain activity in rodents. As part of this, I provide assistance with interpretation of data from analyses of rodent brain.
Collaborator Contribution Provision of empirical data gathered using rodents (mice).
Impact Awarded project grant funding from BBSRC (see Further Funding section).
Start Year 2018
 
Description WT Collaborative Award in Science 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution I am partnering with 2 other Oxford groups, as well as groups at University College London (UK) and the University of Ulm (Germany), as part of a substantial research collaboration focused on defining compartmentalised calcium handling in dopamine neurons and its importance for selective vulnerability in Parkinson's. I acted as a Co-Applicant in the bid for collaborative funding. I lead research efforts directed toward the electrophysiological and photometric interrogation of mouse models of Parkinson's.
Collaborator Contribution Guide and inform our research using mouse models of Parkinson's.
Impact We and our 4 partners have been collectively awarded a Wellcome Trust Collaborative Awards in Science (3.7 million GBP over 5 years). See Further Funding section.
Start Year 2021
 
Description WT Collaborative Award in Science 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution I am partnering with 2 other Oxford groups, as well as groups at University College London (UK) and the University of Ulm (Germany), as part of a substantial research collaboration focused on defining compartmentalised calcium handling in dopamine neurons and its importance for selective vulnerability in Parkinson's. I acted as a Co-Applicant in the bid for collaborative funding. I lead research efforts directed toward the electrophysiological and photometric interrogation of mouse models of Parkinson's.
Collaborator Contribution Guide and inform our research using mouse models of Parkinson's.
Impact We and our 4 partners have been collectively awarded a Wellcome Trust Collaborative Awards in Science (3.7 million GBP over 5 years). See Further Funding section.
Start Year 2021
 
Description WT Collaborative Award in Science 
Organisation University of Ulm
Country Germany 
Sector Academic/University 
PI Contribution I am partnering with 2 other Oxford groups, as well as groups at University College London (UK) and the University of Ulm (Germany), as part of a substantial research collaboration focused on defining compartmentalised calcium handling in dopamine neurons and its importance for selective vulnerability in Parkinson's. I acted as a Co-Applicant in the bid for collaborative funding. I lead research efforts directed toward the electrophysiological and photometric interrogation of mouse models of Parkinson's.
Collaborator Contribution Guide and inform our research using mouse models of Parkinson's.
Impact We and our 4 partners have been collectively awarded a Wellcome Trust Collaborative Awards in Science (3.7 million GBP over 5 years). See Further Funding section.
Start Year 2021
 
Description Banbury Museum & Gallery exhibition 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Some of the Unit's microscopic images, illuminating in beautiful detail the circuits and cells of the mammalian brain, were on public display as part of an exhibition held at the Banbury Museum & Gallery. The exhibition, entitled "Your Amazing Brain: A User's Guide", ran from 12th February to 5th June 2022 and was an interactive, family-friendly experience offering the public an opportunity to journey inside the brain and discover more about what makes the brain so special. The Unit's images, formed the core of a gallery piece "Zoom into your brain" that showcased, at increasing magnification, the organisation of the brain into regions, different types of neurons, and specialised structures such as axons, dendrites, and synaptic connections. Two researchers from my Group provided spectacular shots taken with the Unit's microscopes. One of my group members also led on the curation of the Unit's images for the exhibition. The feedback from the public attending the exhibit was very positive.
Year(s) Of Engagement Activity 2022
URL https://www.mrcbndu.ox.ac.uk/news/units-images-brain-featured-museum-exhibition
 
Description Participation in Medical Research Zone of "I'm A Scientist!" (G.Y.) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact G.Y. (a postdoctoral researcher in my group) participated in the Medical Research Zone of "I'm A Scientist, Stay at home!", a free online outreach event where school pupils meet and interact with medical researchers. Over five weeks in Oct/Nov, G.Y. answered questions submitted by school pupils, and engaged in live online text-based chats with them. Following a competition format similar to the show 'X Factor', the pupils were the judges and voted for their favourite scientists.
Year(s) Of Engagement Activity 2020
URL https://mrcmedical2020.imascientist.org.uk/
 
Description Participation in Medical Research Zone of "I'm A Scientist!" (L.B.) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact L.B. (a student researcher in my group) participated in the Medical Research Zone of "I'm A Scientist, Stay at home!", a free online outreach event where school pupils meet and interact with medical researchers. Over six weeks, L.B. answered questions submitted by school pupils, and engaged in live online text-based chats with them. Following a competition format similar to the show 'X Factor', the pupils were the judges and voted for their favourite scientists.
Year(s) Of Engagement Activity 2020
URL https://mrcmedical2020.imascientist.org.uk/
 
Description Virtual STEM research-experience programme 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Over the summer, researchers at the MRC Brain Network Dynamics Unit (led by a member of my group) delivered an online research-based module, entitled "Interacting with the brain", for school pupils in support of a virtual research-experience programme organised in partnership with the charity in2scienceUK. The module was designed to give pupils insights into brain research and how the Unit contributes to it. The module started with an interactive webinar, during which the pupils were given a broad introduction to neuroscience, the work of the Unit, and the incorporation of animal and human subjects within it (including ethical considerations). There were approximately 60 pupils in attendance (feedback from in2scienceUK suggested this was amongst the more popular modules). Pupils were then given research tasks to take away and complete in their own time, using real data from the Unit, coding tasks, question sheets, notebook and instructions on how to complete it. A second webinar was the held to review the research task. Feedback from pupils and Unit researchers indicated the module was a successful, positive and interesting experience.
Year(s) Of Engagement Activity 2020
URL https://in2scienceuk.org/