University of Oxford Momentum Award – Dementias

Lead Research Organisation: University of Oxford

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

Research and drug discovery for Alzheimer’s disease (AD) is undergoing a minor crisis with a
paucity of novel therapeutic approaches that is human evidence-based. Whilst, human genetic
studies have identified AD associated variants important for CNS glial function, there is
uncertainty over whether inflammation plays a beneficial or deleterious role. As a result, many
pharma companies are hesitant before committing significant resources to this novel therapeutic
opportunity. Our proposal is therefore focused on the scientific theme “Microglial interactions in
Alzheimer’s Disease”. The indicative projects will leverage four key capabilities within the
University of Oxford that represent untapped potential and are ripe for development for dementia
research, (1) access to human primary CNS cell types from human tissue coupled with single
cell analysis, (2) Human iPSC derived microglia, (3) High order imaging analysis of cellular
phenotypes driven by machine learning, (4) Protein-protein interaction disruption to probe
signalling pathways. The proposed projects approaches neuro-inflammation in AD through these
technical capabilities and are supported by world-leading bioinformatics and unrivalled structural
genomics consortium (SGC) pharmacological tools. These tools enable pharmacological pilot
studies within the projects, which if successful, will more rapidly lead to drug discovery projects
because of the enabling structural knowledge and chemical starting points held within the SGC.
Momentum funds will support the recruitment of a new research leader from outside the UK, as
well as supporting early career high flyers within Oxford. Our pharma partners and institution
leverages the MRC funds with significant institutional funds, platforms, space and expertise
totalling ~£2million (~£850K from the institution and $1.5million industry in-kind). We have
developed strong partnerships with Oxford University Hospital NHS Trust and industry including
world-leaders in single cell biology and dementia drug discovery. The Award will support the
diversification of target identification and develop human in vitro models that are more likely to
be predictive of clinical outcomes compared to current dominant murine models. Our approach
will facilitate synergy between disciplines and maximise the contribution of the grant towards the
acceleration of new dementia research in Oxford.

Publications

10 25 50

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Parkes I (2018) Neurovascular dysfunction in dementia - human cellular models and molecular mechanisms. in Clinical science (London, England : 1979)

 
Description EU H2020
Amount € 18,000,000 (EUR)
Organisation European Commission 
Department Innovative Medicines Initiative (IMI)
Sector Public
Country Belgium
Start 09/2018 
End 09/2023
 
Description IM2PACT
Amount € 9,000,000 (EUR)
Funding ID 807015 
Organisation European Union 
Sector Public
Country European Union (EU)
Start 11/2018 
End 10/2023
 
Title IPSC microglia toolkit 
Description A NF kappa beta reporter human iPSC line that can be differentiated into various cells to report on this gene activation eg. in response to TNF alpha 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? Yes  
Impact No impact yet 
 
Title Molecular signatures of microglial activation 
Description 1. IPSC Microglia co-cultures with neurons were exposed to LPS and the single cell gene expression response was assessed using the 10X genomics platform 2. iPSC microglia were exposed to LPS or PGE2 +/- ATP followed by single cell gene expression using the 10X genomics platform 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact None yet 
 
Description IMI IM2PACT 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution This 18 million euro programme is a public-private partnership to develop predictive in vitro and in vivo models of the Blood-Brain-Barrier to improve therapeutic access to the central nervous system. Cader is the Consortium coordinator; Webber is a work-package leader
Collaborator Contribution There are multiple academic institutions and SMEs across Europe involved in this consortium as well large Pharma.
Impact Collaboration is multi-disciplinary. Bioinformatics, stem cell models; pharmacokinetics; tissue engineering; preclinical models; nanotechnology
Start Year 2018
 
Description Purinergic signalling in microglia-neuron interactions 
Organisation Orion Corporation
Country Finland 
Sector Private 
PI Contribution Development of iPSC-microglia models and response to ATP; calcium imaging and multi-electrode array analysis of microglia and neutrons
Collaborator Contribution Funding and experimental design
Impact Assay development
Start Year 2018
 
Description ARUK Dementia Research day talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Invited talk about the Momentum project and microglia for other Dementia Researchers, organised by Alzheimer's Research UK Oxford branch
Year(s) Of Engagement Activity 2017
URL https://www.dpag.ox.ac.uk/research/wade-martins-group/oxford-aruk-network-centre/research-day-2015
 
Description ARUK Oxford Network Research Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presentation to researchers at the University of Oxford, as well as attendees from local industry, sparking discussion of the projects and plans for further interaction with new research groups.
Year(s) Of Engagement Activity 2017
URL https://www.dpag.ox.ac.uk/research/wade-martins-group/oxford-aruk-network-centre/research-day-2015
 
Description Banbury Center (Cold Spring Harbor Labs) Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An expert group meeting to discuss key issues in using stem cell for neuropharmacology and studies of neurodegenerative disorders
Year(s) Of Engagement Activity 2017
 
Description DPUK Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A talk on developing stem cell models and experimental medicine approaches for vascular health in dementia
Year(s) Of Engagement Activity 2017
 
Description Interview on BBC Radio Wales 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Interview discussing how scientists in Wales are at the centre of health research, this interview focused on work aimed at identifying whether people are at risk of developing dementia
Year(s) Of Engagement Activity 2018
URL https://www.bbc.co.uk/programmes/b0b9zrvv
 
Description OPDC Participants Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Oxford Parkinson's Disease Centre Talk to study participants, patients and carers about microglia
Year(s) Of Engagement Activity 2017
URL http://opdc.medsci.ox.ac.uk/podcasts-2017
 
Description PD UK patient forum talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact I gave a PD UK patient forum talk at Waterlooville Community Centre, 10 Maurepas Way, Waterlooville, Hampshire, PO7 7AY. Wed 12/07/2017
"How can skin cells help us find therapeutics for Parkinson's?"
Year(s) Of Engagement Activity 2017
URL https://www.parkinsons.org.uk/
 
Description Parkinson's UK Research Roadshow Cardiff 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Cardiff edition of Parkinson's UK Research Roadshow took place at Hadyn Ellis Building. It was a UK wide event, inviting patients and family members to hear about exciting research taking place at specific locations and providing information on how involvement in research could help move towards better treatments and ultimately a cure. Interactive discussions with patients, carers and charity workers about 'Can stem cells find new treatments for Parkinson's'
Year(s) Of Engagement Activity 2018
URL https://www.healthandcareresearch.gov.wales/noticeboard/parkinsons-uk-research-roadshow-cardiff/?for...
 
Description Pharma collaboration meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Around 15 delegates from J&J attended a meeting at the University of Oxford with research teams engaged in drug discovery for mental health. This was one of a series of meetings that led to the company being part of the MRC Oxford Mental Health Data Pathfinder project.
Year(s) Of Engagement Activity 2017
 
Description Presentation at opening of new Institute 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact Around 250 people attended the opening of the Li Ka Shing Centre for Health Information and Discovery. 7 scientists showcased big data projects, sparking questions and discussion.
Year(s) Of Engagement Activity 2017
URL http://www.ox.ac.uk/news/2017-05-16-world%E2%80%99s-largest-health-big-data-institute-opens-oxford
 
Description Scientific Talk at King's College London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Academic research talk at external institution
Year(s) Of Engagement Activity 2018
 
Description Stem Cell Outreach Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Hosted an activity in a workshop for senior school pupils to learn about human stem cells
Year(s) Of Engagement Activity 2018
URL https://www.path.ox.ac.uk/news/secondary-school-students-peek-real-life-world-stem-cell-research-dun...
 
Description Talk at Basel Life Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited talk about iPS-derived microglia at Basel Life Conference session: Pluripotent stem cells in disease modeling and drug discovery
Year(s) Of Engagement Activity 2017
 
Description Talk at Cardiff Dementia Research Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Scientific talk to the Dementia Research Institute, Cardiff University
Year(s) Of Engagement Activity 2018
 
Description Talk at Oxford Parkinson's Disease Centre Research Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Talk at Oxford Parkinson's Disease Centre Research Day, which attracts delegates from across the region, including both resaerchers, clinicians and patients/carers
Year(s) Of Engagement Activity 2018
 
Description Talk at industry meeting in Belgium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A group from Oxford travelled to meet with Pharma in Belgium to discuss potential opportunities for collaboration, to be followed up.
Year(s) Of Engagement Activity 2019
 
Description Talk to Oxford Immunology Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact Invited talk about microglia to the Oxford Immunology Group Neuroinflammation meeting
Year(s) Of Engagement Activity 2017
URL https://oig.kennedy.ox.ac.uk/
 
Description UK Dementia Research Seminar (Tokyo) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A foreign commonwealth office sponsored visit to Tokyo for 2 days of engagement with Japanese dementia researchers to discuss shared interests and possible collaborations
Year(s) Of Engagement Activity 2017