University of Edinburgh Momentum Award – Dementias

Lead Research Organisation: University of Edinburgh

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

Microglia, the resident macrophages of the central nervous system (CNS), and monocyte-derived cells are critical effectors and sculptors of changes in the CNS environment (1). In recent years, it has become clear that microglia and myeloid cells such as monocytes, macrophages, or dendritic cells are ontogenetically and also functionally distinct innate immune cell populations in the CNS. The goal of my research is to characterize the heterogeneity of CNS myeloid cells and to determine their differential functions in neurodegenerative diseases.
Using multiplexed single-cell mass cytometry (CyTOF), we have characterized the phenotypic signature of human microglia, which is distinct from myeloid cells in the cerebrospinal fluid and peripheral blood (2). Notably, we detected significant regional heterogeneity of human microglia. We are currently combining CyTOF with another high-dimensional technique (scRNA-seq) to investigate the context-specific adaptive responses of microglia during pathology. This approach will enable us to identify and characterize previously unknown microglia subsets in the human brain, their spatial distribution, and their changes with aging and neurodegeneration.
In a second line of research, we are establishing a novel CNS-conditioned in vitro model of human microglia using patient-derived induced pluripotent stem cells (iPSCs) in collaboration with Siddharthan Chandran’s group at the DRI. This approach will enable us to study the dynamic changes of microglia that occur in neurodegenerative diseases as a result of genetic mutations and environmental changes. It will also provide us with the opportunity to model the context-specific adaptive responses of microglia that we detect in the human brain, and to explore their potential pathogenetic relevance in neurodegenerative diseases.
We hope that the characterization of disease-associated microglia subtypes in the human CNS will open new avenues for subset-specific therapeutic interventions in neuropsychiatric disorders.

Publications

10 25 50
 
Guideline Title Chorea Leitlinie
Description EHDN
Geographic Reach Europe 
Policy Influence Type Citation in clinical guidelines
Impact Treatment guideline for movement disorders
 
Description Neuropsychiatry Committee DGPPN
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Improvement in the services provided for patients with neuropsychiatric disorders, training and education in neuropsychiatry, establishment of national and international treatment guidelines
 
Description Update Neuropsychiatry DGPPN
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Annual workshops for medical care professionals at the DGPPN annual meetings
 
Description BIH Platform Humanized Model Systems
Amount € 35,000 (EUR)
Organisation Charité - University of Medicine Berlin 
Sector Academic/University
Country Germany
Start 01/2019 
End 12/2019
 
Description Peripheral monocytes for central nervous system remyelination
Amount £176,629 (GBP)
Funding ID C012-19.1 
Organisation Multiple Sclerosis Society 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2020 
End 12/2021
 
Description SFB-TR167 B05,B07,IRTG
Amount € 10,600,000 (EUR)
Organisation German Research Foundation 
Sector Charity/Non Profit
Country Germany
Start 01/2017 
End 12/2020
 
Title Mass cytometry for human CNS tissue 
Description The technique can be used to investigate different myeloid cell populations in the human brain using 50-70 markers. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact Böttcher et al., Nat Neurosci 2019 
 
Description CCBS, Prof. Chandran 
Organisation University of Edinburgh
Department Centre for Clinical Brain Sciences (CCBS)
Country United Kingdom 
Sector Academic/University 
PI Contribution Funding and supervision of PhD student and postdoc, consumables, lab space
Collaborator Contribution Funding and supervision of staff, consumables
Impact Banerjee et al., submitted for publication Presentations at national conferences
Start Year 2017
 
Description CDBS, Dr. Barry McColl 
Organisation University of Edinburgh
Department Centre for Discovery Brain Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Staff, consumables, expertise
Collaborator Contribution Expertise
Impact FENS educational symposium 2020
Start Year 2017
 
Description CDBS, Dr. Dirk Sieger 
Organisation University of Edinburgh
Department Centre for Discovery Brain Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Funding and supervision of staff, consumables, equipment
Collaborator Contribution Co-supervision of staff, provision of lab equipment
Impact None yet
Start Year 2018
 
Description MRC Center for Regenerative Medicine, Prof. Williams 
Organisation University of Edinburgh
Department MRC Centre for Regenerative Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-supervision of PhD student, provision of human biosamples, funding of sequencing costs
Collaborator Contribution Lab space, expertise, consumables
Impact None yet
Start Year 2019
 
Description Microglia dynamics in CNS regeneration 
Organisation University of Edinburgh
Department MRC Centre for Reproductive Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of lab space, animal model and consumables
Collaborator Contribution PhD student performed experiments in my lab, established in vitro remyelination assay
Impact Lloyd et al., Nat Neuroscience (2019), thesis prize
Start Year 2017
 
Description QMRI, Dr. Miron and Dr. Pridans 
Organisation University of Edinburgh
Department Queen's Medical Research Institute Edinburgh
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-supervision of students, funding and supervision of staff, consumables, lab space
Collaborator Contribution Co-supervision of students, consumables, lab space
Impact Lloyd et al., Nat. Neurosci 2019 Scientific presentations at meetings
Start Year 2017
 
Title EGCG in Huntington"s disease 
Description Phase 2 randomised, placebo-controlled, multi-centre trial on 1200 mg EGCG/day in patients with Huntington's disease, IIT (DFG funding) 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2015
Development Status Closed
Clinical Trial? Yes
Impact Pharmacokinetic data in HD patients 
URL https://clinicaltrials.gov/show/NCT01357681
 
Description EHDN 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lead facilitator in Working Group on Symptomatic Treatment and Research
Year(s) Of Engagement Activity Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018
 
Description Extended Board member, DGGPP 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact German Society for Geriatric Psychiatry
Year(s) Of Engagement Activity 2019,2020
 
Description Interview for national news (Spiegel, Welt am Sonntag) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Explanation of clinical trial results
Year(s) Of Engagement Activity 2017,2018
 
Description Neuropsychiatry Committee DGPPN 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chair of the Neuropsychiatry Committee, DGPPN
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015,2016,2017,2018