MRC Brain Banks: Joint Application to Underpin Neuroscience Research

Lead Research Organisation: University of Oxford
Department Name: Clinical Neurosciences

Abstract

This application plans to support research into the causes and potential treatment of a range of diseases affecting the
brain, some of which have been identified as priorities for research, such as dementia. The UK has a network of
established Brain Banks that provide human tissue samples to a wide range of researchers. Human tissue samples have
allowed a better understanding of the mechanisms operating in these complex disorders and have already aided the
development of treatments for Alzheimer's disease and Parkinson's disease.
This application will support four Brain Banks in Edinburgh, London, Newcastle and Oxford. These banks each have areas
of particular interest, Parkinson's disease, Alzheimer's disease and motor neurone disease. However, in addition to the
collection of tissues samples from patients with brain disorders, it is also essential to collect normal tissue samples for use
as controls in research. Two of the Banks have a major focus in this area, so this application will support the collection of
both disease and normal tissue samples.
The banks will support scientific research by providing human tissue samples in an efficient and cost effective manner,
while ensuring the samples provided are of the high quality required by researchers. The banks have worked to improve
their efficiency, reducing the time required to provide the samples to researchers. Details of the samples available in each
of the banks are included in a database, which is accessible through the internet. This allows researchers to see what
samples are available and how to request these samples for their research in an easy way that will save time and speed up
progress.
All four Brain Banks in this application have approval form an Ethics Committee, to ensure that their working practices meet
nationally agreed standards that apply to work with human tissue samples. The work of each Bank is overseen by a local
steering committee that includes members of the public and ethics experts as well as scientists and pathologists. Brain
Banking is expensive, but the operating costs of these four banks are far less than their equivalents in Europe and in the
USA.
The challenges of developing treatments for complex diseases such as Alzheimer's disease and Parkinson's disease are
considerable, but the Brain Banks in this application will play an important role in underpinning the scientific research in
these national priority areas.

Technical Summary

This joint application from the MRC Brain Banks in Edinburgh, London, Newcastle and Oxford is submitted in accordance
with the wishes of the MRC Neuroscience and Mental Health Board (NMHB). After the last funding round for the MRC
Brain Banks in 2011, NMHB indicated that a future joint application would be preferred and that the applicants should
demonstrate progress in efficiency and improving standards of work in accordance with an agreed set of metrics. This
application fulfils this request, and aims to underpin neuroscience research in the UK by providing high-quality human brain
tissue samples and data in the formats required by researchers in both academic and industrial settings. The four banks in
this application together cover the collection of human tissue samples from a range of major neurological diseases, and
normal tissue samples to act as controls. This provides an invaluable resource to underpin neuroscience research in UK,
particularly in recently identified priority areas such as dementia.
The banks have demonstrated in this application that they can work to the standards set in the metrics agreed with the
NMHB, and have improved their efficiency of operations. The banks already support a number of major researchers in
academia and industry in UK and overseas, including several who are currently funded by MRC. The provision of high
quality tissue samples and accompanying data is essential for the success of these projects; the MRC brain banks
constitute a critical infrastructure for this research.
In order to develop this important work further, funding for a 5 year period is requested; earlier funding awards for periods
of 2 years has not been conducive to long term planning and strategy. The costs of brain banking in the UK compare very
favourably with those in Europe and in the USA; over the next 5 years the banks will continue to work to improve efficiency
of operation and to operate a cost recovery programme in keeping with MR

Planned Impact

The activities of the brain banks will be of major significance to neuroscience researchers in the UK and the banks plan to
capitalise upon this by promoting the availability of their tissue samples during the course of this grant, primarily by the
MRC database, which will give details of all samples currently available, including control samples. This promotion will not
be confined to academic researchers, but also through the Association of British Pharmaceutical Industries the applicants
will promote the availability of the tissue samples in their banks and will engage with both academic and industrial
researchers to help provide the samples they require.
The brain banks already supply tissue samples to commercial companies for their research and development purposes and
it is planned to continue and develop these contacts within an appropriate framework.
The applicants are involved in a number of local, national and international committees and bodies that relate to research.
Policymakers within both government (DH) and non-governmental organisations and regulators (e.g. the Human Tissue
Authority) will benefit from information arising from the use of human brain tissue samples and also from the general
promotion of brain donation in neuroscience research.
The applicants have previously engaged with museums (including the Wellcome Trust museum) and charities including the
Alzheimer's Society, Alzheimer's Research UK, the Multiple Sclerosis Society and Parkinson's UK to provide expert advice
on brain banking. The applicants also work within the committee structure of these charities to advise on their research
activities, particularly those that might involve the collection and use of human tissue samples.
The wider public is likely to benefit from this planned research, particularly if the tissue samples provided result in improved
diagnosis or treatment for patients with neurodegenerative disorders. Furthermore, the promotion of brain banking and the
value of brain donation for research will help raise public awareness of the challenges of dementia and neurodegenerative
diseases, and help make individuals take an informed choice on this complex matter.
It is likely that the government may benefit from this research, particularly in respect to the activities of the Ministerial Action
Group on Dementia Research and the Prime Minister's Challenge on dementia, within which brain banking is
acknowledged as an essential requirement to support researchers in this field. The support requested in this application
will be of wider benefit to these government initiatives and the research arising from this work, supported by other
government funded bodies including NIHR.
Finally, MRC is likely to benefit from this research, since the applicants already provide large numbers of tissue samples to
researchers such as Professor John Hardy, UCL, who are in receipt of significant funding from MRC to undertake research
projects that are critically dependent on a continuous supply of high quality tissue samples that will be collected and made
available during the course of this proposal.

Publications

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Al-Mashhadi S (2015) Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain. in Brain pathology (Zurich, Switzerland)

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Alexopoulou Z (2016) Deubiquitinase Usp8 regulates a-synuclein clearance and modifies its toxicity in Lewy body disease. in Proceedings of the National Academy of Sciences of the United States of America

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Baek JH (2016) Unfolded protein response is activated in Lewy body dementias. in Neuropathology and applied neurobiology

 
Description Tissue Donation in the OUH Hospitals
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Staff training and patient information concerning tissue donation after death has been rolled out across the OUH Hospitals as a result of our project.
 
Description Brains for Dementia Research
Amount £498,000 (GBP)
Organisation Alzheimer’s Brain Bank UK 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2013 
End 04/2018
 
Title Brain and spinal cord Tissue for Research 
Description The principle aim of this research project (G1000691) is to provide national and international researchers with high-quality biological samples with associated clinical and quality data. 
Type Of Material Biological samples 
Year Produced 2011 
Provided To Others? Yes  
Impact Tissue is being used in a range of projects by academic and industry partners. Output data (samples etc) are available through a regulated requesting system. 
 
Title Developed microproteomic technology for human brain (motor cortex and cerebellum) analysis 
Description Analysing the proteome of specific cell types in an unbiased fashion is technically challenging. We have developed a novel way of obtaining up to 2500 proteins from as few as 200 cells of the human brain. This will help us in dissecting in more detail what makes specific cells vulnerable to neurodegenerative disease like MND. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact Our method has been adopted by several local and international research groups. 
URL https://www.ncbi.nlm.nih.gov/pubmed/30768908
 
Title Liquid nitrogen vapour freezing 
Description Protocol for systematic, rapid freezing of anatomically preserved slices of human brain tissue using a liquid nitrogen vapour storage/transportation dewar. 
Type Of Material Improvements to research infrastructure 
Year Produced 2013 
Provided To Others? Yes  
Impact Pilot analysis suggests greater preservation of microscopic anatomy and no ice crystal artefacts. Accurate dissection of frozen region of interest facilitated by preserved anatomy of coronal slices. Freezing method adopted or about to be adopted by other centres (Edinburgh, Autism BrainNet nodes) 
 
Title Thomas Willis Brain Collection database 
Description This is a database of all brain, spinal cord and peripheral organ tissue available for research within the Oxford Brain Bank's Thomas Willis Brain Collection. The archive contains over 6,000 cases from the 1960s to present. The data is available to researchers through Brain UK. 
Type Of Material Database/Collection of data 
Year Produced 2011 
Provided To Others? Yes  
Impact We regularly receive requests from researchers for tissue of patients with rare conditions 
 
Description Autism BrainNet 
Organisation Autism Speaks
Department Autism BrainNet
Country United States 
Sector Charity/Non Profit 
PI Contribution Autism BrainNet have offered the Oxford Brain Bank the opportunity to become the first non-USA node of the Autism BrainNet network, with a start date of 1st January 2015. The tissue to be retrieved includes brains from patients with Autism and other related developmental diseases, as well as young controls with sudden death or diseases outside the nervous system.
Collaborator Contribution Funding will be provided on a per brain basis for retrieving and making the tissue available to the network for research.
Impact Partnership starting January 2015
Start Year 2014
 
Description Alzheimer Research UK Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact A full day with ~150 attendees about clinical and 'translational' brain research with a focus on dementia. Presentation and discussion on the importance of brain banking to understand pathogenesis and outcomes of treatments etc.

Interest by the public to explore tissue donation - reflected in pick-up of leaflets and discussions.
Year(s) Of Engagement Activity 2013
 
Description Autism Research Oxford Workshop 
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 Workshop gave rise to an offer by Autism BrainNet for Oxford Brain Bank to join their network, and served as a platform for discussing Autism Research in Oxford

Dr Ansorge invited Autism BrainNet's project manager to visit the Oxford Brain Bank facilities, she visited in July. Dr Ansorge then visited the facilities of the New York node of the network and met up with all other node directors.
Year(s) Of Engagement Activity 2014
 
Description Brain Awareness Week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact An afternoon of interactive activities with Oxford researchers and students from Oxford University Cortex Club as part of Brain Awareness Week. Drop-in suitable for children aged 6 upwards.

The activities ranged from video games explaining the pathophysiology of Alzheimers Disease, to live microscope and EEG demonstrations.
Year(s) Of Engagement Activity 2016
URL http://www.mhs.ox.ac.uk/gastrophysics-brain-aware/
 
Description British Association for Tissue Banking 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact Presentation of rationale, ethical framework and strategy for brain banking to the national annual meeting of the BATB.

Better integration of tissue donation for transplant and research. Understanding that these two activities can be linked.
Year(s) Of Engagement Activity 2012
 
Description Invited Q&A 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Science Oxford screened the Oscar-nominated documentary Life, Animated - A mix of animated storytelling and real life narration that doesn't flinch from exploring the emotional highs and lows that accompany a life with autism. The screening was "followed by a talk by University of Oxford neuroscience expert Steven Chance". SThe Ultimate Picture Palace and Science Oxford invited him to speak and do Q&A. Over 80 people in the audience attended for the Q&A and asked questions. As a result he has also been invited to speak at a secondary school by one of the teachers who attended.
Year(s) Of Engagement Activity 2016
 
Description MRC Bbank Network Donation Workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Very useful workshop concerning potential, risks, experiences and ethical considerations about UK brain banking. Discussion with funders, users and scientists.

Development of a coherent strategy for UK brain tissue banking for neuroscience research.
Year(s) Of Engagement Activity 2013
 
Description NIHR BRC Oxford Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Poster Presentation
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Presentation to the public of the link between researching and understanding common brain diseases and human brain tissue donation.

Increase in enquiries about brain tissue donation by memebers of the public.
Year(s) Of Engagement Activity 2012
 
Description Oxford Brain Bank Open Day 
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 80 participants visited the Oxford Brain Bank. During the day they attended a talk about tissue banking by Dr Ansorge, visited the Neuropathology laboratory and were shown brain anatomy and how Alzheimer's disease affects brain morphology with Professor Esiri, learnt about tissue preparation with Oxford Brain Bank technicians, looked at brain pathology down the microscope with Dr Ansorge, learnt about new techniques and equipment in tissue banking with Connor Scott, and talked about research outputs and research projects with Dr De Luca.

The participants were very enthusiastic about the event and many reported wanting to engage more with the Oxford Brain Bank and to read more about research outputs related to brain and spinal cord donation. Several relatives of donors were present and reported a greater understanding of the processes that follow brain donation.
Year(s) Of Engagement Activity 2015
 
Description Oxford Parkinson's UK group site visit 
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 "Value of brain banking and what Neuropathology can teach us about Parkinson's disease?"

Oxford Parkinson's disease group are now aware of and supportive of brain banking efforts
Year(s) Of Engagement Activity 2011
 
Description Parkinson's Disease Local Branch Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Education of patients and relatives as well as health care professionals about the impact brain tissue research has made on our understanding of the pathobiology of Parkinson's disease and other degenerative conditions.

Raised public awareness of our project.
Year(s) Of Engagement Activity 2011
 
Description Test For Parkinson's Disease Moves Step Closer 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Media article printed on BBC website.
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/news/health-37196619
 
Description Visit from The London International Youth Science Forum (LIYSF) 
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 Undergraduate students
Results and Impact LIYSF is a two week residential event held at Imperial College London, with lectures and demonstrations from leading scientists, visits to industrial sites, research centres, scientific institutions and organisations, including world class laboratories and universities.

LIYSF attracts 500 of the world's leading young scientists aged 17-21 years old from more than 65 participating countries. There is an active social calendar with events designed to enable those from around the world to learn about different cultures. The scope of LIYSF extends further than broadening scientific understanding to engage students in education on other cultures and develop lasting, international friendships.

30 students visited the Neuropathology laboratory and enjoyed a teaching session on brain anatomy and pathology with Dr Ansorge.
Year(s) Of Engagement Activity 2015
URL http://www.liysf.org.uk/