Wednesday 11 March 2020

Royal College of Physicians of Edinburgh

@EdinUniNeuro #EdinNeuroDay Neuroscience Day 2020 Supporters

2 Programme

08.30 Arrival and Registration

Session 1 Chaired by: Professor Siddharthan Chandran, Director, Edinburgh Neuroscience

09.00 Welcome Prof Siddharthan Chandran, Director, Edinburgh Neuroscience 09.05 The Edinburgh City Deal: Opportunities for Data-Driven Innovation at Scale Professor Aziz Sheik, Usher Institute 09.30 Troubled translation in autism Dr Emily Osterweil, Centre for Discovery Brain Sciences 09.55 Neuroanatomy of Core Language Systems: A Data-Driven Journey Dr Dan Mirman, Psychology 10.20 Shout-outs, Edinburgh Innovations, the CMVM Impact team, UK Centre for Mammalian Synthetic Biology 10.30 Coffee & Posters

Session 2 Chaired by: Dr Sue Fletcher-Watson, Salvesen Mindroom Research Centre

11.00 Fellows Session Elucidating RNA metabolism changes in neurological disease, Dr Chris Sibley, Sir Henry Dale Fellow, Centre for Systems and Synthetic Biology and Simons Initiative for the Developing Brain Astrocytes in health and disease, Dr Blanca Diaz-Castro, Programme Leader (Fellow), UK Dementia Research Institute at Edinburgh Dissecting neural circuits underlying cognition: An in vivo single-cell physiology approach, Dr Jian Gan, Programme Leader (Fellow), UK Dementia Research Institute at Edinburgh People and place memory recruits distinct regions of human medial parietal cortex, Dr Edward Silson, Lecturer in Visual Perception, Psychology

12.00 The rise and fall of microglia driving central nervous system remyelination, Dr Veronique Miron, Centre for Reproductive Health 12.25 Psychosis & contextual vulnerability: developmental pathways to risk & resilience, Professor Matthias Schwannauer, Clinical Psychology 12.50 WT Translational Neuroscience PhD Programme - TN2, Professor Stephen Lawrie, Programme Director, Centre for Clinical Brain Sciences

12.40 Lunch & Posters (1.45pm, New Library, short presentation for supervisors on the Translational Neuroscience PhD programme and those PIs interested to find out more)

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Session 3 Chaired by: Professor Anna Williams, MRC Centre for Regenerative Medicine

14.15 Student Data Blitz An integrated study of placenta, blood and brain MRI implicates IL-8 dysregulation in preterm brain injury, Ms Gemma Sullivan, Centre for Reproductive Health Pre-symptomatic developmental phenotypes in Spinal Muscular Atrophy, Ms Anna Motyl, Centre for Discovery Brain Sciences Single cell immune profiling in stroke identifies target cellular states for precision medicine, Mr Anirudh Patir, Centre for Discovery Brain Sciences and UK Dementia Research Institute The effects of sleep/wake cycles on the synaptome maps of the mouse brain, Ms Dimitra Koukaroudi, Centre for Clinical Brain Sciences

14.40 Brain signatures of depression, Dr Heather Whalley, Centre for Clinical Brain Sciences

15.05 Generation Scotland – supporting health data neuroscience across the life-course, Professor David Porteous, Institute for Genetics & Molecular Medicine

15.30 Tea & Posters

Session 4 Chaired by: Professor Siddharthan Chandran, Director, Edinburgh Neuroscience

16.00 Annual Distinguished Lecture in Neuroscience 2020 Retinal repair through transplantation of ES-derived photoreceptor cells: a vision for the future, Professor Robin Ali, Professor of Human Molecular Genetics, Institute of Ophthalmology, Faculty of Brain Sciences, University College London

17.00 Drinks Reception in the Conference Centre Foyer

18.00 Close of Meeting

4 Edinburgh Neuroscience Activity Round Up 2020

It has been another busy and exciting year and that is thanks to the energy, engagement and enthusiasm of our neuroscience researcher community – thank you everyone!

A successful year that bodes well for the future

Over the past year, our researchers have had a number of large funding successes which provide a platform for building a portfolio of exciting research projects into the future. These include: £15.3 million donation from author J.K. Rowling to support the Anne Rowling Regenerative Neurology Clinic, (Director: Prof Siddharthan Chandran) which was set up following a previous donation in 2010, and is named in memory of her mother who died of MS, aged 45. This generous new gift will help create new facilities and support vital research focusing on MS and neurological conditions such as motor neurone disease, Parkinson's, and dementias, aiming to support and conduct clinical studies and trials. It will also support projects focusing on the invisible disabilities experienced by people with MS, such as cognitive impairment and pain. Following the retirement of Shuna Colville as ARRNC Manager last year, Judy Newton has now taken on this role. ARRNC website. £12 million from the Simons Foundation secures the future of the Simons Initiative for the Developing Brain (SIDB) (Director: Prof Peter Kind) from 2022 – 2025. This advanced renewal is a particularly welcome investment since it allows for long term experimental planning for a major programme of fundamental and clinical autism research, over a timeframe that can encourage the development of innovative experimental approaches. SIDB website. £12.1 million from Cancer Research UK and The Brain Tumour Trust to researchers in the Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine for projects to investigate which drugs best target glioblastoma, one of the hardest types of cancer to treat because not enough is known about what starts and drives the disease. Prof Neil Carragher was awarded £6.3M to identify and target the best drug combinations which target these aggressive brain tumours. He will be working with colleagues at MIT to develop prototype nanoparticles which are able to cross the blood-brain barrier and carry multiple drugs at the same time. Dr Steven Pollard was awarded £5.8M to investigate how to prevent tumours from growing back by trying to control the movement of dormant cancer cells to active ones. CRUK EC website £5.5 million from Wellcome to fund the PhD Programme in Translational Neuroscience for 5 further intakes of students, starting in September 2020. This was the only Wellcome funded neuroscience-related PhD programme in the UK to be renewed. Prof Stephen Lawrie will take over as Lead Director of ‘TN2’, supported by co-directors Prof David Price, Prof Tara Spires-Jones, Prof Peter Kind, Prof Anna Williams, and Dr Sue Fletcher-Watson. TN2 website €6 million to establish a new Fondation Leducq international consortium, Stroke-ImPACT, which will investigate the role of neuroimmune mechanisms influencing cognitive trajectory after stroke. Eleven researchers from nine institutions in four countries, including Dr Barry McColl (UK Dementia Institute at Edinburgh and Centre for Discovery Brain Sciences), will establish an international network of stroke researchers and trained young researchers in the field, plus collate an international resource of clinical and pre-clinical data to enable discovery of new ways of preventing post-stroke cognitive decline over the next 5 years. Stroke-ImPACT news announcement $0.5 million from the Alzheimer's Drug Development Foundation global philanthropist funded (including Bill Gates) Diagnostics Accelerator Program for a project led by Dr Tom MacGillivray with Prof Craig Ritchie, Prof Bal Dhillon and Dr Graciela Muniz Terrera (all Centre for Clinical Brain Sciences). Aimed at delivering novel neuro-retinal biomarkers for the early diagnosis of Alzheimer’s disease, this study will employ a novel combination of retinal biomarkers capturing neurodegeneration and vasculature dysfunction often found in Alzheimer's disease with advanced imaging analyses. ADDF news announcement The Euan MacDonald Centre and partners launched UK recruitment for a new clinical trial MND-SMART. The trial, led by Prof Siddharthan Chandran and Dr Suvnakar Pal (both Centre for Clinical Bran Sciences) has been designed to find effective medicines more quickly, and be adaptive so that the researchers can modify their approach according to emerging results. Initially researchers will test drugs that are already licensed for use in other conditions to check whether they offer any benefit for people with MND. This launch was the top news item on BBC news and has now registered 20% of the total UK MND patient pool. MND-SMART website

5 New Initiatives that promise new horizons

AstronauTx Ltd, secured £6.5 million from the Dementia Discovery Fund, a Venture Capital Fund dedicated to dementia-orientated start-ups to spin-out the company which will target astrocytes to restore their homeostatic function as treatments for dementias. Prof Giles Hardingham is the scientific co-founder and advisory board member and the company will focus on targets arising from work conducted by Prof Paul Whiting at the University College London Alzheimer’s Research UK Drug Discovery Institute, as well as the UK Dementia Research Institute at Edinburgh. AstronauTx news announcement Pheno Therapeutics is a new spin-out company focussed on multiple sclerosis which has secured a £5 million commitment over three years from Advent Life Sciences (London-based venture capital firm), the Scottish Investment Bank (with the backing from the Scottish Government through the Scottish Growth Scheme) and independent medical research charity LifeArc. Co-founded by Prof Siddharthan Chandran (Centre for Clinical Brain Sciences) and Prof Neil Carragher (Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine) the company will search for new drugs that aim to repair damage to the nervous system and significantly improve patients’ debilitating symptoms. Pheno Therapeutics website Strategic support from Edinburgh Innovations – how they can help you. Edinburgh Innovations (EI) is the ’s commercialisation service. They work with CMVM to help achieve the College’s strategic vision of creating an environment in which academic and commercial values are aligned and directed through a strong culture of translation and commercialisation to promote impactful contributions that address current challenges for patients, health and care, and society. So how is EI doing this for Neuroscience? Dr Jane Redford ([email protected]) has recently joined the Business Development team in EI in November 2019, and is now ‘embedded’ within Edinburgh Neuroscience. Jane R has a background in Neuroscience, having previously worked in academia and a range of commercial companies. Whilst Jane R is the primary point of contact within the EI for Neuroscience, she works closely with other account team members who can provide expertise in areas such as IP, Consultancy, Company formation and Entrepreneurship. Jane R divides her time between Bio Quarter, George Square and the Institute of Psychiatry. She holds weekly drop-in sessions for anyone seeking help with any aspect of translation and commercialisation: • 2.30-3.30 pm, Monday in JexBlake, Chancellor’s Building • 11am-12 pm, Wednesday in the Common Room, Hugh Robson Building. Jane R is happy to meet individuals one-to-one, discuss ideas by phone and email, or attend lab meeting to provide more information on EI and guidance on any prospective projects. So why engage with Edinburgh Innovations? Think of all the innovative ideas you may have around your research on a daily basis. Could any of these be ‘exploited’ and translated into a commercial plan? This is where EI can help you. They can look for potential University and commercial collaborators to help you address these questions, provide information on funding opportunities, look at whether your work could be licensed or patented and, ultimately, even help with the formation of a new company. Horizons in Neuroscience was a meeting facilitated by Edinburgh Innovations and organised Prof Tara Spires-Jones and Prof Catherina Becker (both Centre for Clinical Brain Sciences). It brought together industry researchers and academics last month to discuss barriers to translation and to profile the resources and cutting-edge research undertaken in Edinburgh. With over 100 attendees, it was a really interesting and stimulating meeting and a great start to our closer relationship with Edinburgh Innovations and industrial partners. Helping Hand is a new App launched by the Salvesen Mindroom Research Centre. It enables parents, and carers of children, who have been referred for assessment in Scotland, to record relevant information, such as sleeping patterns and challenging behaviour, about their child. Autism assessment can be complicated, lengthy and involve numerous professionals across a series of appointments and assessments. The hope is that the app could improve the process by giving clinicians a clearer insight into a child’s behaviour and thereby reduce the stress on parents, carers and children. The app is currently being piloted in NHS Lothian. Helping Hand news announcement

6 Mental health research and training in Malawi is an exciting series of initiatives consisting of the Scotland Malawi Mental Health Education Project (a Scottish Charity partnered with College of Medicine at University of Malawi) which received over £1 million funding from Scottish Government and is supported by academics and administrators from the Division of Psychiatry. This project has delivered psychiatry teaching to about 800 Malawian medical students and established a psychiatry postgraduate training programme. Recent pump-priming funding has established the African Alliance for Maternal Mental Health, a pan-African collaboration for education, advocacy and service development, which has now led to the formation of £3.8 million MRC-GCRF funded Generation Malawi project. This is led by Prof Andrew McIntosh and includes a new Senior Clinical Research Fellow, Dr Robert Stewart, who is based in Malawi. Generation Malawi has partnered with Wellcome funded Healthy Lives Malawi project (based at the University of Glasgow) to create a unique intergenerational longitudinal population study of long-term mental and physical health conditions, conducted in close partnership with Malawi institutions. The idea is that this will lead to creation of a world-leading dataset and a platform for the training of a cadre of expert researchers in Malawi. Generation Malawi information

Supporting career development and new research directions with pump priming funds

McGill - Edinburgh partnerships: Neuroscience Day 2019 saw the launch of a new research partnership between McGill University and Edinburgh Neuroscience focused around the areas of autism/neurodevelopmental disorders, intellectual disabilities (with particular focus on studies using human induced pluripotent stem cells), and neurodegenerative diseases. Three awards, each with a value of £45,000 (C$80,000) were awarded to: • Development of functional thalamocortical circuitry in a rat model of fragile X syndrome – Dr Adrien Peyrache (McGill) and Dr Emma Wood (Centre for Discovery Brain Sciences, Edinburgh). • Drug screen for modulators of neuro-inflammation in spinal cord injury – Prof Sam David (McGill) and Prof Catherina Becker (Centre for Discovery Brain Sciences, Edinburgh) • Electrophysiological analysis of human stem cell-derived neurons: establishing a cross-institutional core facility – Prof Derek Bowie (McGill) and Prof David Wyllie (Centre for Discovery Brain Sciences, Edinburgh)

RS Macdonald Seedcorn Fund: In 2019, £30,220 was awarded to eight projects and, in a one-off opportunity, an additional £19,896 was awarded to six projects that focussed on epilepsy. • Network abnormalities in a new mouse model of genetic epileptic encephalopathy – Prof Cathy Abbott and Dr Alfredo Gonzalez-Sulser (Muir Maxwell Epilepsy Centre) • Genetic Causes in Adults with Intellectual Disability – Pilot Study – Dr Lindsay Mizen (Patrick Wild Centre) • Role of microglia in the development of epilepsy and associated anatomical damage – Dr Neela Codadu, Dr Alfredo Gonzalez-Sulser, and Dr Clare Pridans (Muir Maxwell Epilepsy Centre and Patrick Wild Centre) • Probing protein-protein interactions during activity-dependent bulk endocytosis with FRET-FLIM – Dr Daniela Ivanova (Muir Maxwell Epilepsy Centre) • Understanding microglial response to amyloid beta under different aggregation states – Dr Michael Daniels (UK Dementia Research Institute at Edinburgh) • The developmental arrival of cerebroventricular and choroid plexus macrophages – Dr David Munro (UK Dementia Research Institute at Edinburgh) • Using the Zebrafish to Identify Genetic Modifiers of C9ORF72 linked neurodegeneration – Dr Marcus Keatinge (Euan MacDonald Centre for MND Research) • New Positron Emission Tomography (PET) imaging biomarker for non-invasive imaging of oligodendrocyte activity in health and during disease – Dr Adriana Tavares, Prof Ruth Andrew, Prof Kevin Lynch (Centre for Cardiovascular Science) • Surgical delivery of therapeutics to large mammalian (non-primate) brains – Dr Tom Wishart (Roslin Institute) • Astrocyte heterogeneity in CD44 expression as a novel discriminatory marker for neurodegenerative diseases – Dr Barry Bradford (The Roslin Institute) • The role of VAPB-ion channel associations in governing neuronal activity – Dr Mandy Jackson (Euan MacDonald Centre for MND Research)

7 • The onset and progression of cognitive and behavioural changes in amyotrophic lateral sclerosis (ALS) and related disorders – Dr Caroline McHutchison (Euan MacDonald Centre for MND Research) • Enhancing a GPU server for the development of neuroimaging machine learning – Dr Grant Mair and Dr Gerard Thompson (Centre for Clinical Brain Sciences) • Characterisation of a rat model for ALS8 – Dr Paul Skehel (Centre for Discovery Brain Sciences)

Neuroresearchers Fund: In 2019 were able to award £2,955 to four Edinburgh Neuroscience researchers and all were part-funded by a generous donation from the guests at the wedding of Hanna and Patrick Hillan (both former neuroscience Honours students in Edinburgh). • Dr Miruna Barbu (Postdoc, Centre for Clinical Brain Sciences): visit to Icahn School of Medicine Mount Sinai, New York, to attend a training course and spend time in Prof Sophia Frangou's laboratory to learn computation psychiatry techniques and start a new collaboration. • Dr Sarah McGlasson (Postdoc, UK Dementia Research Institute at Edinburgh): visit the laboratory of Prof Wilbur Lam, Emory University School of Medicine to learn the technical details of a microvascularture-on-a- chip model. • Sau Yee Tsoi (Research Assistant, Centre for Discovery Brain Sciences) to visit the headquarters of Visiopharm in Denmark to be trained in the use of the software used to execute feature detection through deep leaning, and visualize data from her experiments.

Henderson Scholarships: In 2019 we were able to award 5 scholarships to allow undergraduate students to work on a neuroscience summer project in a laboratory in the Deanery of Biomedical Sciences. • Exploring the variability in sensitivity to modulation of synaptic strength by magnesium across the larval drosophila neuromuscular junction – Molly Hickey (BSc (Hons) Pharmacology, 4th year) with prof Richard Ribchester • Functional recovery of locomotor circuits following spinal cord injury in Xenopus tadpoles – Ara Kim, with Dr Honyan Zhang (BSc (Hons) Neuroscience, 3rd year) • Does reducing sensory stimulation after learning improve long-term hippocampal memory in a rat model of Fragile X Syndrome? - Łucja Kostrzewa (BSc (Hons) Neuroscience, 3rd year) with Dr Emma Wood • Exploring mechanisms of mechanotransduction using a transgenic tarantula toxin - Yilan Shen (BSc (Hons) Physiology, 3rd year) with Dr Barry Denholm • The role of Pax6 in the process of cortical cell specification - Ariam Teklemichael (BSc Medical Sciences, 2nd year) with Dr Michael Daw

8 In 2019/20 congratulations went to:

Lots and lots of our researchers so we have only have room for a small selection here:

Prof Malcolm Macleod (Centre for Clinical Brain Sciences) has been appointed University Academic Lead for Research Integrity and Improvement. He will work with colleagues to recognise best practice, identify areas which might be further improved, and support improvement initiatives. Dr Sue Fletcher-Watson (Centre for Clinical Brain Sciences) who was appointed Director of the Salvesen Mindroom Research Centre last year. SMRC website Prof David Hunt on his promotion to Professor of Neuroinflammatory Medicine

Prof Tom Gillingwater (Centre for Discovery Brain Sciences) on his election as a Fellow of the Royal Society of Edinburgh. Professor Charles ffrench-Constant (Centre for Regenerative Medicine) on being awarded the University of Edinburgh 2019 Chancellor's Research Award Dr Tilo Kunath (Centre for Regenerative Medicine), on winning the Tom Isaacs Award 2019 for his research into Parkinson's Disease, and for his empathy and enthusiastic engagement with the Parkinson's community

Dr Jane Haley (Edinburgh Neuroscience Coordinator) on being made a Member of the Order of the British Empire in the Queen’s Birthday Honours 2019 Dr Emily Osterweil (Centre for Discovery Brain Sciences) and Dr David Hunt (Centre for Clinical Brain Sciences) who both had successful applications for a Wellcome Senior Research Fellowship. Dr Nathalie Rochefort (Centre for Discovery Brain Sciences) and Dr Pleasantine Mill (Institute for Genetics & Molecular Medicine) who have both successfully been awarded European Research Council Consolidator Grants.

Not forgetting ……….

New books published: Dr Jennifer Paxton (Centre for Discovery Brain Sciences) has published a new anatomy book ‘Anatomicum’ (Big Picture Press) which describes the wonder and beauty of the human body. Prof Gareth Leng (Centre for Discovery Brain Sciences) also has a new book coming out next month, which is published with his son. ‘The Matter of Facts’ (MIT Press) explores how biases, the desire for a good narrative, reliance on citation metrics, and other problems undermine confidence in modern science. Anatomicum webpage, Matter of Facts webpage Linking with parliament: Over the past year three students have undertaken internships at the Scottish or Westminster Parliaments – Maggi Laurie (Centre for Clinical Brain Sciences), Helen Corby (Alzheimer’s Scotland Dementia Research Centre) and Gabrielle King (Usher Institute), while Dr Gashirai Mbizvo (Clinical Research Fellow, Muir Maxwell Epilepsy Centre) presented his PhD work on the Scottish Epilepsy Deaths Study (SEDS) at a Cross Party Group meeting at Scottish Parliament. Neurone vs Neuron: For years we have used different spellings, so should it be ‘neuron’ or ‘neurone’? The reason for preferring one spelling over the other is usually assumed to reflect American (neuron) versus British (neurone) usage. Dr Arpan Mehta (Centre for Clinical Brain Sciences) has traced the origins of the name and published etymological arguments supporting the view that the correct, and only, spelling is ‘neuron’! Paper in Brain

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Neuroscience Day 2020 Speakers

2020 Annual Distinguished Lecturer

Professor Robin Ali

Professor of Human Molecular Genetics, Institute of Ophthalmology, Faculty of Brain Sciences, University College London

[email protected]

Prof Ali’s website

Retinal repair through transplantation of ES-derived photoreceptor cells: a vision for the future Robin Ali is Professor of Human Molecular Genetics at UCL Institute of Ophthalmology. He is also Theme Leader for Gene Therapy at NIHR Biomedical Research Centre, Moorfields Eye Hospital and until recently Director of the Wolfson Gene Therapy Unit, a UCL GMP facility for manufacturing clinical grade gene therapy vectors. He is also Visiting Professor at Kellogg Eye Center, University of Michigan and Founder and ex-Chief Scientific Officer of MeiraGTx, a UK incorporated gene therapy company with offices in London and New York. The company has secured substantial investment to develop a path to market for a number of ocular gene therapies licensed from UCL and in June 2018 become a publicly listed company on the NASDAQ exchange. The main focus of Robin Ali’s research is the development of gene and cell therapy for the treatment of retinal disorders. Since 1996, he has published over 200 peer-reviewed papers with landmark papers and preclinical proof- of-concept (POC) studies for many different ocular disorders. As chief investigator, he established the world’s first clinical trial of gene therapy for retinopathy. The results from this trial reporting an improvement in vision (NEJM, 2008; NEJM 2015) along with results from two other trials, established POC for gene therapy for inherited retinal degeneration. His group has also provided the first POC for effective transplantation of photoreceptors (Nature 2006; Nature, 2012) that has provided the basis for ES cell-derived photoreceptor transplantation (Nature Biotech 2013), now a major programme in his laboratory. Robin Ali and members of his team have received numerous prizes and awards for their work on developing new treatments for retinal degeneration, including the The Champlaimaud Vison Award (2018), Pfizer/ARVO Translational Award for Ophthalmology (2010), the Alcon Research Institute Award (2009) and in 2014, Human Gene Therapy journal’s Pioneer Award. In 2007 he was elected to the Academy of Medical Sciences and in 2009 elected NIHR Senior Investigator. He is a recent past President of the European Society of Gene and Cell Therapy and has served on the advisory boards of a number of funding bodies including the UK Medical Research Council and Research to Prevent Blindness USA as well as advisory boards of several pharmaceutical and biotech companies, including Alcon/Novartis.

11 2020 Speakers (in programme order)

Professor Aziz Sheikh

Professor of Primary Care Research & Development

Usher Institute

[email protected]

The Edinburgh City Deal: Opportunities for Data-Driven Innovation at Scale

Aziz Sheikh is Professor of Primary Care Research & Development and Director of the Usher Institute at The University of Edinburgh. He is Honorary Consultant in Paediatric Allergy at the Royal Hospital for Sick Children, NHS Lothian, Director of the 16-university Asthma UK Centre for Applied Research, Director of the NIHR Global Respiratory Health Unit (RESPIRE), Director of the Scottish Allergy and Respiratory Academy, PI on the NIHR Programme Grant for Applied Research on ePrescribing systems for Anti-Microbial Stewardship (ePAMS+), and is Co-Director of the NHS Digital Academy. Aziz has substantive academic and health policy interests in leveraging the potential of health information technology and data science to transform the delivery of health care and improve population health, which have led him to work with numerous governments, the World Health Organization (WHO) and the World Bank. He serves on the Steering Group and as Chair of the Evaluation Group of the WHO’s 3rd Global Safety Challenge on Medication Safety and is an adviser to the WHO’s Eastern Mediterranean Regional Office. He is an editorial board member of PLOS Medicine, Medical Care, Health Informatics Journal and BMC Medicine. He was Guest Editor of PLOS Medicine’s recent theme issue on Machine Learning in Healthcare and Biomedicine and BMC Medicine’s recent theme issue on Big Data in Healthcare. He serves on The Lancet’s Commission on the Future of the NHS. He chaired the World Innovation Summit for Health (WISH) Forum on Data Science and Artificial Intelligence in Healthcare. He served on the UK’s Research Excellence Framework (REF) for Medicine in 2014 and is again serving on this expert panel for REF 2021. Aziz has, together with colleagues across the world, held research grants in excess of £100m, has over 1,000 peer- reviewed publications, and has a H-index of >100. His co-edited books include Health Care Errors and Patient Safety (Wiley, 2009), Patient Safety and Healthcare Improvement at a Glance (Wiley, 2014), Landmark Papers in Allergy: Seminal Papers in Allergy with Expert Commentaries (Oxford University Press, 2013), Middleton's Allergy Essentials (Elsevier, 2016), and Key Advances in Clinical Informatics (Elsevier, 2018). He has given keynote and plenary presentations in over 40 countries and has won numerous national fellowships and awards including a Harkness Fellowship in Health Policy and Practice based at Brigham and Women’s Hospital/Harvard Medical School (2013-14). He held the position of Visiting Professor of Medicine at Harvard Medical School (2014-16) and currently holds visiting chairs at the University of Birmingham (UK), Queen Mary’s University of London (UK) and Maastricht University (the Netherlands). He is Co-Director of Harvard Medical School’s Safety, Quality, Informatics Leadership (SQIL) Program. Aziz has been honoured with fellowships from 8 learned societies, including the Fellowship of the Royal Society of Edinburgh and Fellowship of the Academy of Medical Sciences. He is a founding Fellow of the UK’s Faculty of Clinical Informatics. Aziz was made an Officer of the Order of the British Empire for ‘Services to Medicine and Health Care’ by Her Majesty Queen Elizabeth II in 2014. He was in 2017 awarded the American Public Health Association’s Donabedian Award and The University of Edinburgh’s Principal’s Medal for Exceptional Services. He was in 2018 inducted into HighlyCited.com and was recently inducted into ISQua’s International Academy of Quality and Safety.

@DrAzizSheikh

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Dr Emily Osterweil

Wellcome Trust Sir Henry Dale Fellow

Centre for Discovery Brain Sciences

[email protected]

Troubled translation in autism.

Emily Osterweil is a molecular neuroscientist investigating how the synthesis of new proteins in neurons contributes to brain function. She was awarded a Wellcome Trust Sir Henry Dale fellowship in 2014 to start her independent research at the University of Edinburgh, focusing on the role of unbalanced synaptic protein synthesis in multiple genetic models of autism. These studies identified novel therapeutic strategies that are currently being tested in clinical trials for fragile X syndrome and autism. She was recently awarded a Wellcome Trust Senior Research fellowship to continue her work and use new molecular techniques to identify novel therapeutic strategies. Before joining the University of Edinburgh Dr Osterweil received her PhD from Yale University and performed postdoctoral research at MIT.

Dr Dan Mirman

Senior Lecturer

Psychology

[email protected]

Neuroanatomy of Core Language Systems: A Data-Driven Journey

Dan received his PhD in Psychology in 2005 from Carnegie Mellon University and the Center for the Neural Basis of Cognition. His doctoral work combined behavioural experiments with computational modelling to study how auditory perception and language knowledge interact during speech perception. During his post-doctoral fellowship at the University of Connecticut he learned eye-tracking methods for on-line measurement of speech comprehension and began to study how semantic knowledge is organized in the mind. In 2009 he joined the Moss Rehabilitation Research Institute (MRRI) and began his research on the neural organization of spoken language processing in individuals with language deficits following stroke (aphasia). He taught in the US at Drexel University and the University of Alabama at Birmingham before joining the Department of Psychology at the University of Edinburgh in 2019. Dan’s current research is motivated by the real-world problem of neurogenic language impairments and aims to address fundamental questions about the neurobiology of language, focused on three broad topics: (1) the neuroanatomy of spoken language processing, (2) the organization of semantic knowledge, and (3) the role of cognitive control in language processing. He also work to increase the rigor, reproducibility, and transparency of psychological and neural sciences.

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Dr Chris Sibley

Wellcome Trust Sir Henry-Dale Fellow

Centre for Systems and Synthetic Biology and Simons Initiative for the Developing Brain

[email protected]

Elucidating RNA metabolism changes in neurological disease

Dr Sibley’s research group aim to understand how RNA is regulated in the CNS in both health and disease. A diverse range of wet and dry-lab techniques are used to achieve this using human tissue and stem cell models of both ALS and Autism. Accordingly, the group has positioned itself to work at the interface of systems biology, RNA biology and molecular neuroscience. The lab moved to Edinburgh University in May 2019 with the support of the Wellcome Trust, Royal Society and Simons Initiative for the Developing Brain.

Dr Blanca Diaz-Castro

Programme Leader (Fellow),

UK Dementia Research Institute at Edinburgh

[email protected]

Astrocytes in health and disease

Dr Blanca Diaz-Castro obtained her PhD degree at the University of Seville - Institute of Biomedicine of Seville (IBiS) under the supervision of Dr. Jose Lopez-Barneo and Dr. Jose Ignacio Piruat. After a brief stay at Northwestern University, Chicago, in Dr. Peter Penzes lab, she completed her postdoctoral research at University of California, Los Angeles with Dr. Baljit Khakh. Blanca’s career has been centred on the study of molecular and cellular aspects of astrocyte biology that contribute to neuronal function in health and disease. During her training, she developed an interest on the close relationship of astrocytes with the brain vasculature. As a programme leader at the UK DRI - University of Edinburgh, Blanca’s research focuses on the relationship between vascular disease and dementia. She is using her expertise on astrocyte biology towards the understanding of how blood brain barrier cells communicate with each other and act as a bridge between the periphery and the brain..

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Dr Jian Gan Programme Leader (Fellow),

UK Dementia Research Institute at Edinburgh

[email protected]

Dissecting neural circuits underlying cognition: An in vivo single-cell physiology approach

Dr Jian Gan is a cellular/systems neuroscientist. After obtaining his PhD from the University of Glasgow, he went on to work in the lab of Prof. Peter Jonas in the University of Freiburg, Germany and later Institute of Science and Technology Austria in Vienna, where he employed and optimised in vivo high-resolution patch-clamp recording technique to elucidate synaptic mechanism of hippocampal oscillations that are essential for spatial coding and memory consolidation in awake mice. He went on to gain further experience in implementing well-controlled quantitative cognitive behaviours for mice in virtual reality with high-density population recording in the lab of Prof. Thomas Klausberger at the Medical University of Vienna, before he set up his own lab in the University of Edinburgh, funded by a UKDRI fellowship. Jian’s lab is very much interested in clarifying real-time synaptic transmission dynamics and its resulting population coding schemes underlying cognitive processes such as oscillations, spatial coding, and simple decision making in vivo. With such knowledge, the lab sorts to elaborate on what, where, when and how such dynamism goes wrong in disease conditions such as dementia.

Dr Edward Silson Lecturer in Visual Perception, Psychology

Centre for Clinical Brain Sciences

[email protected]

People and place memory recruits distinct regions of human medial parietal cortex,

My work investigates the interaction between visual perception and memory and uses a multi-disciplinary approach. I combine functional magnetic resonance imaging (fMRI), with transcranial magnetic stimulation (TMS) and behavioral psychophysics to probe the neural mechanisms underpinning visual perception and how those mechanisms interact with memory processes. My work mainly involves healthy individuals, but I also work on understanding the impact of retinal diseases, such as macular degeneration and choroideremia, on cortical organisation

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Dr Veronique Miron,

Senior Lecturer

Centre for Reproductive Health

[email protected]

The rise and fall of microglia driving central nervous system remyelination

Dr. Veronique Miron is a Senior Lecturer and MRC Career Development Fellow at The Queen’s Medical Research Institute. Her research focus is on investigating the regenerative properties of inflammation in driving myelin regeneration, working towards identification of novel treatments for neurological diseases characterized by white matter injury (e.g. multiple sclerosis, cerebral palsy, and other neurodegenerative disorders). More specifically, her work has shown that dynamic changes in microglia and macrophage function is critical for efficient remyelination, and that these are dysregulated in disease. Her lab’s recent work has revealed a novel regenerative factor produced by microglia that controls the oligodendrocyte lineage throughout the lifespan (activin-A), and novel mechanisms that regulate the generation of pro-regenerative microglia (death). Current work is focused on understanding how these processes which control efficient remyelination are dysregulated when white matter does not repair properly in development (e.g. following perinatal brain injury) or aging (e.g. in neurodegenerative disease), how other cell types contribute to microglia behaviour after injury and complement their function (astrocytes, monocytes), and how we can target these cells and processes/cells with drugs to support repair. Dr. Miron is an Athena Swan champion and has been awarded the Suffrage Science award in Life Sciences this year.

Professor Matthias Schwannauer

Professor of Clinical Psychology

Clinical Psychology

[email protected]

Psychosis & contextual vulnerability: developmental pathways to risk & resilience

Matthias Schwannauer, MA, MSc, DPsych, PhD, CPsychol, AFBPsS, Head of School of Health in Social Science and Professor of Clinical Psychology at The University of Edinburgh, graduated in clinical and applied psychology from the University of Marburg in 1998, with internships in Marburg, The Free University Berlin, the Sigmund Freud Institute in Frankfurt as well as NHS Scotland. His first position as a qualified clinical psychologist was in the Adoelscent Mental Health Services in Glasgow. He moved to NHS Lothian and the University of Edinburgh in 2000. His research group is focused on investigating developmental trajectories of mental health and well being across the life span and the development of current psychological models of emotional distress and mental health. His research interests include the application of attachment theory, reflective function and psychological processes in relation to neurodevelopmental processes to further our understanding of the development, adaptation to and recovery from severe mental health conditions, particular psychosis and recurrent mood disorders. He is particularly interested in the advancement of specific psychological interventions. Matthias is Principal Investigator in a number of randomised controlled trials of psychological interventions for severe and enduring mental health problem in adolescents as well as adults.

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Dr Heather Whalley

Senior Research Fellow in Neuroimaging

Centre for Clinical Brain Sciences

[email protected]

Brain signatures of depression

Heather is a Senior Research Fellow in Neuroimaging at the Centre for Clinical Brain Sciences. Her research aims to improve the understanding of core pathophysiological processes underlying risk, resilience, to psychiatric disorders by integrating genomic, cognitive and neuroimaging techniques.

Professor David Porteous

Chair of Human Molecular Genetics and Medicine

Centre for Genomic and Experimental Medicine, Institute for Genetics & Molecular Medicine and Centre for Medical Informatics, Usher Institute

[email protected]

Generation Scotland – supporting health data neuroscience across the life- course

David has a long-standing interest in psychiatric genetics as a path towards understanding the biological underpinning of schizophrenia, bipolar disorder and major depressive disorder. His group is perhaps best known for the discovery of DISC1 as a risk factor for psychiatric illness and the role DISC1 plays in brain development and synaptic plasticity. He is also the originator and Principal Investigator for Generation Scotland, a population and family based cohort designed to study the genetic and environmental determinants of health. The cohort currently comprises 24,000 adults in 7,000 family groups. Participants answered detailed questions about their medical history, education, thinking skills, mental health, occupation, lifestyle and habits. Participants attended a clinic visit, donated urine, serum and blood for DNA studies, gave consent for linkage to their NHS medical records and for us to recontact them for follow on studies. Generation Scotland will be the focus of David’s talk today, illustrating how they have been able to support a wide range of neuroscience projects, including the £4.9M Wellcome Trust funded ‘Stratifying Resilience and Depression Longitudinally (STRADL)’ project led by Professor Andrew McIntosh. With the recent award of £5.1M from the Wellcome Trust, they are preparing to double the size for the cohort, recruit younger members and add new data linkages that will create a birth-to-death study platform through which to research the genetic and physical determinants of physical and mental health. He will tell you how you can influence the questions we ask of participants and how to apply for access to the derived data. Our aim is to support the best possible science at the least added cost and effort for researchers.

17 PhD Student Data Blitz Talk Abstracts

An integrated study of placenta, blood and brain MRI implicates IL-8 dysregulation in preterm brain injury Gemma Sullivan1, Paola Galdi1, Manuel Blesa Cabez1, Nis Borbye-Lorenzen2, David Q. Stoye1, Gillian J.Lamb1, Margaret Evans3, Alan Quigley4, Michael Thrippleton5,6, Kristin Skogstrand2, Siddharthan Chandran5,7, Mark E. Bastin5, James P. Boardman1,5 1MRC Centre for Reproductive Health, University of Edinburgh, 2Statens Serum Institut, Copenhagen, Denmark, 3Department of Pathology, Royal Infirmary of Edinburgh, 4Department of Radiology, Royal Hospital for Sick Children, Edinburgh, 5Centre for Clinical Brain Sciences, 6 Edinburgh Imaging, University of Edinburgh Background: Systemic inflammation during perinatal life contributes to white matter disease in preterm infants. Histologic chorioamnionitis (HCA) is associated with white matter disease and cerebral palsy but the mediators that drive this association are poorly understood, which limits development of neuroprotective strategies. Methods: Participants were 102 preterm infants (mean postmenstrual age 29+2 weeks, range 23+3-32+0). A customised immunoassay of 24 inflammatory proteins was performed using umbilical cord and postnatal day 5 blood. Placental histopathology identified reaction patterns indicative of HCA. Structural and diffusion brain MRI scans were acquired at term-equivalent age and white matter integrity was calculated using peak width skeletonised mean diffusivity (PSMD) and neurite density index (PSNDI). Result and Conclusions: Cord blood IL-8 was identified as a sensitive predictor of HCA in preterm infants (AUC= 0.917 95% CI 0.841-0.993, p<0.001) and postnatal day 5 IL-8 was negatively associated with white matter maturity at term- equivalent age. These findings provide new evidence that IL-8 dysregulation links systemic inflammation during perinatal life and atypical white matter development in preterm infants. Acknowledgements: This work was supported by Theirworld (www.theirworld.org) and was completed in the MRC Centre for Reproductive Health, at the University of Edinburgh.

Pre-symptomatic developmental phenotypes in Spinal Muscular Atrophy Anna A.L. Motyl1,2, Kiterie M.E. Faller3, Ewout J.N. Groen4, Samantha L. Eaton5, Rachel A. Kline2,5, Leire M. Ledahawsky1,2, Helena Chaytow1,2, Douglas J. Lamont6, Thomas M. Wishart2,5, Yu-Ting Huang^,1,2, Thomas H. Gillingwater^,1,2 1Edinburgh Medical School: Biomedical Sciences, 2Euan MacDonald Centre for Motor Neurone Disease Research, 3Royal (Dick) School of Veterinary Studies, University of Edinburgh, 4UMC Utrecht Brain Center, University Medical Center, Utrecht, Netherlands, 5The Roslin Institute, University of Edinburgh, 6FingerPrints Proteomics Facility, University of Dundee ^&* These authors contributed equally Spinal muscular atrophy (SMA) is a leading genetic cause of infant death, characterised primarily by a loss of lower motor neurons. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene. New SMN-restoring therapies for SMA have emerged in recent years; however, data from both pre-clinical and clinical studies demonstrate that there is a limited therapeutic time-window for them to be effective. Moreover, it is now clear that peripheral organs and tissues can also be affected by the disease. To better understand the earliest changes occurring during SMA, with implications for defining the optimum time and location of therapy delivery, we undertook a detailed anatomical, histological and molecular analysis of pre- symptomatic, prenatal changes occurring in a mouse model of SMA. We generated 3D-renderings of whole embryos at embryonic day [E]14.5 using µCT. These analyses showed that SMA embryos are significantly smaller than littermate controls, indicative of a general developmental delay. Morphometric and histological analyses showed no overt structural defects indicative of degenerative pathology in any of the organs examined. We then performed a comparative translatome screen of spinal cord, brain, liver, skeletal muscle and heart in SMA and control mice using Tandem Mass Tagging mass spectrometry. This revealed significant molecular perturbations in all organs examined. Notably, we found a lack of overlap in affected proteins and molecular pathways between organs, highlighting tissue- specific prenatal molecular phenotypes in SMA. Together, our data demonstrate that considerable changes are already present across numerous tissues and organs at an early, pre-symptomatic stage in SMA mice, suggesting that there is a significant developmental component to SMA pathogenesis. Funders: Medical Research Council

18 Single cell immune profiling in stroke identifies target cellular states for precision medicine Anirudh Patir1, Stefan Szymkowiak2, Lucas Lefevre2, Caoimhe Kirby2, Victoriana Poon2, Adrian Olmos-Alonso2, Prakash Ramachandran3 and Barry McColl2, 1The Roslin Institute, University of Edinburgh, 2UK Dementia Research Institute at Edinburgh, Chancellor’s Building, , 3Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh Stroke, a leading cause of death and disability with limited treatments, induces a marked neuroinflammatory response (1). A critical challenge is to develop immunomodulatory treatments that harness pro-repair immune cell activity while minimising deleterious inflammatory effects. To help achieve this, we immunoprofiled the brain after stroke, studying cell ontology, phenotype and spatial distribution, using unbiased single cell RNA-Seq with spatial analysis in preclinical and human stroke. We detected a combination of cell types/states unique to the acute stroke neuroinflammatory environment while also finding phenotypes similar to those identified in chronic neurodegenerative models. Here, microglia presented a combination of activated and proliferative states, while monocyte-derived cells differentiated into two trajectories partly overlapping yet distinct from microglial phenotypes. Notably, the induction of a lipid-scavenging and -metabolism associated gene network within one discrete monocyte-derived macrophage population was exemplified by highly restricted expression of Gpnmb. GPNMB protein, implicated in tissue repair (2), showed a similarly restricted expression pattern in human stroke tissue. These data reveal unprecedented insight into acute stroke-induced neuroinflammation through single cell- resolved immunophenotyping providing a rational basis for a more precise approach to stroke immunomodulatory therapy and specific molecular/cell targets such as GPNMB to enable this. This work was funded by MRC, Alzheimer’s Research UK, BBSRC, and the UK Dementia Research Institute. 1) Iadecola et al., Nat Med 2018 17:796-808 2) Campana et al., J Immunol. 2018 200:1169-1187

The Effects of Sleep/Wake cycles on the Synaptome Maps of the Mouse brain Dimitra Koukaroudi, Ricky Qiu, Erik Fransén, Noboru Komiyama, Seth Grant Centre for Clinical Brain Sciences, University of Edinburgh, KTH Royal Institute of Technology, Sweden Sleep, a vital behaviour that synchronises neuronal activity across the whole brain, is known to be a key modulator of learning and memory (Banks & Dinges, 2007; Rasch & Born, 2013). However, sleep modulation of synaptic plasticity, a core brain mechanism for memory regulation, remains a mystery (Gorgoni et al., 2013; Seibt & Frank, 2019). The goal of this project is to unveil the effects of sleep, wakefulness and sleep deprivation on synaptic plasticity by studying three closely interacting synaptic plasticity molecules; Activity-regulated cytoskeleton-associated protein (Arc), Post-Synaptic Density protein 95 (PSD95) and Synapse-Associated protein 102 (SAP102). To fulfil this goal, we process the brains of mice that carry fluorophore-tagged Arc, PSD95 and SAP102 following wakefulness, sleep and sleep deprivation, and implement the SYNMAP technique (Zhu et al., 2018), a method which documents the distribution, density, size, shape and other parameters of these proteins across multiple brain regions. Our data so far clearly show that although sleep is considered a phenomenon of brain-wide synchrony, its synaptic plasticity effects are highly region- and phase-duration-specific, implying an intricate relationship between sleep and synaptic plasticity. Banks, S., & Dinges, D. F. (2007). Behavioral & physiological consequences of sleep restriction. J Clinical Sleep Medicine, 3(5), 519–528. Gorgoni, M., D’Atri, A., Lauri, G., Rossini, P. M., Ferlazzo, F., & De Gennaro, L. (2013). Is Sleep Essential for Neural Plasticity in Humans, and How Does It Affect Motor and Cognitive Recovery? Neural Plasticity, 2013, 1–13. https://doi.org/10.1155/2013/103949 Rasch, B., & Born, J. (2013). About sleep’s role in memory. Physiological Reviews, 93(2), 681–766. doi.org/10.1152/physrev.00032.2012 Seibt, J., & Frank, M. G. (2019). Primed to Sleep: The Dynamics of Synaptic Plasticity Across Brain States. Frontiers in Systems Neuroscience, 13(February), 1–19. doi.org/10.3389/fnsys.2019.00002 Zhu, F., Cizeron, M., Qiu, Z., Benavides-Piccione, R., Kopanitsa, M. V., Skene, N. G., … Grant, S. G. N. (2018). Architecture of the Mouse Brain Synaptome. Neuron 99:781-799.e10. doi.org/10.1016/j.neuron.2018.07.007 Acknowledgement of funders: University of Edinburgh, MRC

19 Posters

Posters can be found in two areas: The Great Hall (on first floor) (posters numbered 1 – 18) and the Conference Centre foyer (posters numbered 19 – XX) Posters in Great Hall (upstairs) Development & Regeneration

1. The role of microglia in developing white matter health Niamh B. McNamara, Clare Pridans, Veronique E. Miron Centre for Reproductive Health, Centre for Inflammation Research 2. Transcriptional analysis of astrocytes reveals protective functions during remyelination Irene Molina-González, Z. Jiwaji, G. Hardingham, S. Chandran, V. Miron Centre for Reproductive Health, Centre Discovery Brain Sciences, Centre for Clinical Brain Sciences, UK Dementia Research Institute, University of Edinburgh 3. Contribution of monocyte-derived macrophages to remyelination Dr Lindsey H Forbes, Dr Claire L Davies & Dr Veronique E Miron Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh 4. The Joubert gene INPP5E acts as a negative regulator of Sonic Hedgehog signalling in human brain organoids Leah Schembs1, Ariane Willems2, Bhuvaneish Selvaraj2, James Cooper2, Sunniva Bostrand1, Kerstin Hasenpusch- Theil1, Karen Burr2, Siddharthan Chandran2, Thomas Theil1 1Centre for Discovery Brain Sciences, 2Centre for Clinical Brain Sciences, University of Edinburgh 5. Investigating the Effects of 16p11.2 Deletion on Cerebral Development and Interneuron Production Using Ventral Telencephalic Organoids Rana Fetit1, Mandy Johnstone2, Stephen Lawrie2, Thomas Theil1, Thomas Pratt1, David Price1 1Simons Initiative for the Developing Brain, Centre for Discovery Brain Sciences, 2Centre for Clinical Brain Sciences, University of Edinburgh 6. Using Cerebral Organoids to investigate the role of Foxg1 in forebrain development Jonothon J. Marshall1., Lara Hobbis1., John O. Mason1.2. 1Centre for Discovery Brain Sciences, 2Simons Initiative of the Developing Brain, University of Edinburgh 7. Raising awareness of a rare genetic condition though public outreach L Jiménez-Sánchez1*, A Edmondson-Stait1*, DA Gadd1*, SA Kent1*, MDE Sewell1*, OM Rifai1*, D Price1, J Sheppard2. *Equally contributing authors 1WT Translational Neuroscience PhD Programme, University of Edinburgh, 2FOXG1 UK (Charity Registration Number: 1167988). 8. Impact of maternal obesity and hyperglycaemia on the developing brain Kahyee Hor1, Emily Herzstein1, Giles Hardingham1 and Amanda Drake2 1Centre for Cardiovascular Science, 2Centre for Discovery Brain Sciences, University of Edinburgh 9. A novel model of early life stress is associated with profound alterations in hypothalamic DNA methylation and stress- induced hyperactivity Eamon Fitzgerald1, Matthew Sinton1, Nicholas M Morton1, Megan C Holmes1, James P Boardman2, Amanda J Drake1 1British Heart Foundation Centre for Cardiovascular Science, 2MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh 10. Neuronal activity disrupts myelinated axon integrity in the absence of NKCC Katy LH Marshall-Phelps1,^, Linde Kegel1,^, Marion Baraban1, Rafael G Almeida1, Maria Rubio-Brotons1, Anna Klingseisen1, Silvia Benito-Kwiecinski1, Jason J Early1, Jenea Bin1, Daumante Suminaite1, Matthew R Livesey1, Richard J Poole2 and David A Lyons1 1Centre for Discovery Brain Sciences, University of Edinburgh, 2Department of Cell and Developmental Biology, University College London, London

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11. Oligodendrocytes that survive demyelination exhibit a limited capacity to form new myelin sheaths Sarah Neely1, Jill Williamson1, Anna Klingseisen1, Jason Early1, Lida Zoupi2, Anna Williams2, and David Lyons1 1.Centre for Discovery Brain Sciences, 2.MRC-Centre for Regenerative Medicine, University of Edinburgh 12. The role of Fractalkine in oligodendroglial-microglial crosstalk and its effect on remyelination in multiple sclerosis Sowmya Sekizar, Catriona Ford, Anna Williams Scottish Centre for Regenerative Medicine, University of Edinburgh 13. High-Content Drug Screening in Human iPSC-Derived Oligodendrocytes Identifies Novel Pathways to Promote Oligodendrocyte Differentiation Telford-Cooke L.L., Magnani D., Longden J., Dawson J., Burr K., Story D., Chandran S., Carragher N. Centre for Clinical Brain Sciences, Institute of Genetics and Molecular Medicine, UK Dementia Research Institute at Edinburgh, Euan MacDonald Centre for Motor Neurone Disease Research, Anne Rowling Regenerative Neurology Clinic, University of Edinburgh 14. Human iPSC-derived myelinoids for investigation of myelin disorders and adaptive myelination Owen G. James1,2,3, Bhuvaneish T. Selvaraj1,2,3,4, Dario Magnani1,2,3, Karen Burr1,2,3, Peter Connick1,2,5, David Story1,2,3, Robert Smiegel6, Rafal Ploski7, Peter J. Brophy8, Charles ffrench-Constant9, David Lyons8, Siddharthan Chandran 1,2,3,4 1UK Dementia Research Institute at Edinburgh, 2Centre for Clinical Brain Sciences 3Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh 4Centre for Brain Development and Repair, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India 5Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, 6Department of Pediatrics and Rare Disorders, Wroclaw Medical University, 7Department of Medical Genetics, Medical University of Warsaw, 8Centre for Discovery Brain Sciences 9MRC Centre for Regenerative Medicine, University of Edinburgh

Neural Systems & Circuits

15. Myelin’s contribution to neuronal circuitry Daumante Suminaite, Jenea M. Bin, Megan E. Madden, Matthew R. Livesey, David A. Lyons. Centre for Discovery Brain Sciences, University of Edinburgh 16. Input-output relationship in CA1 pyramidal neurons reveals compensatory mechanisms in a mouse model of Fragile X Syndrome Laura Simões de Oliveira1,2,3*, Sam A. Booker1,2,3*, Natasha Anstey1,2,3,5, Zrinko Kozic1,3*, Owen R Dando1,2,3,4,5, Adam D Jackson1,2,3,5, Paul S Baxter1,4, Lori L Isom6, Diane Sherman1, Giles E Hardingham1,4, Peter J. Brophy1, David J.A. Wyllie1,2,3,5*, Peter C. Kind1,2,3,5* 1Centre for Discovery Brain Sciences, 2Simons Initiative for the Developing Brain, 3Patrick Wild Centre for Autism Research, 4UK Dementia Research Institute, University of Edinburgh, 5Centre for Brain Development and Repair, InStem, Banglore, India; 6Department of Pharmacology, University of Michigan Medical School, USA 17. The Head Direction Circuit of Two Insect Species Ioannis Pisokas School of Informatics, University of Edinburgh 18. Anatomical and functional specificity of baso-amygdala projections to the entorhinal cortex Christina Brown, Matthew Nolan Centre for Discovery Brain Sciences, Hugh Robson Building, University of Edinburgh

21 Posters in Conference Centre Foyer Cellular & Molecular

19. Generation Scotland: Research-Ready Biomedical Resource Archie Campbell, Rebecca Dawson, Rachel Edwards, Chloe Fawns-Ritchie, Robin Flaig, Louise Hartley, Cliff Nangle, Ian Deary, Caroline Hayward, Andrew McIntosh, Cathie Sudlow, and David Porteous, Generation Scotland, Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, Psychology, Division of Psychiatry, Centre for Medical Informatics, Usher Institute, University of Edinburgh. 20. Neuronal activity state governs the age-related decline of cognitive plasticity Qiaochu Li, Karl Emanuel Busch, Centre for Discovery Brain Sciences, University of Edinburgh 21. NMDA receptor composition and function in interneurons of the rat hippocampus Sam A Booker, Zrinko Kozic, Katie Marwick, Owen R Dando, Giles E Hardingham, Peter C Kind, David JA Wyllie, Patrick Wild Centre for Autism Research (all), Simons Initiative for the Developing Brain (all), UK Dementia Research Institute (ORD, GEH); Centre for Discovery Brain Sciences, University of Edinburgh 22. Axonal hotspots of vesicle release regulate myelination in vivo Rafael Almeida, Jill Williamson, Megan Madden, Jason Early, David Lyons, Centre for Discovery Brain Sciences, University of Edinburgh 23. VAMP4 knockout mice display reduced activity-dependent bulk endocytosis and decreased high frequency excitatory neurotransmission Katharine L. Dobson, Daniela Ivanova, Elizabeth C. Davenport, Daniela Hacker, Michael A. Cousin, Centre for Discovery Brain Sciences, University of Edinburgh 24. Oligodendrocyte heterogeneity with age, sex and region in the post-mortem human CNS Luise A. Seeker1, Sarah Jaekel1, Alastair M. Kilpatrick1, Fabio Baldivia Pohl2, Catalina Vallejos3, Goncalo Castelo- Branco2, Anna Williams1, 1MRC Centre for Regenerative Medicine, University of Edinburgh, 2 Laboratory of Molecular Neurobiology, Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden, 3 MRC Human Genetics Unit, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh. 25. The influence of TREM2 on CNS myeloid cell reactivity and resolution of acute brain inflammation Clare H. Latta, Claire L. Davies and Barry W. McColl UK Dementia Research Institute, Centre for Discover Brain Sciences, University of Edinburgh 26. Investigating microglial lysosome function and the role of cystatin F in inflammation and neurodegenerative disease Michael JD Daniels, Lucas Lefevre, Caoimhe Kirby, Makis Tzioras, Barry McColl, UK Dementia Research Institute at University of Edinburgh

Degeneration and Neuropathology

27. Systemic inflammation enhances activated astrocyte heterogeneity and accelerates neurodegeneration Barry M. Bradford1, David S. Donaldson1, Christianus A. Wijaya1, Kathryn J. Else2 & Neil A. Mabbott1 1The Roslin Institute & Royal (Dick) School of Veterinary Sciences, University of Edinburgh, 2 Lydia Becker Institute of Immunology and Inflammation, School of Biological Sciences, University of Manchester 28. Microglia inhibit astrocyte-mediated neurodegeneration and pericyte calcification Barry M. Bradford1, David A. Hume2, Clare Pridans3 & Neil A. Mabbott1 1The Roslin Institute and R(D)SVS, University of Edinburgh, 2Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, Australia, 3Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh

22 29. Role of microglial reactivity in resilience to chronic cerebrovascular dysfunction Stefan Szymkowiak1, Karen Horsburgh2, Barry McColl1 1UK Dementia Research Institute at Edinburgh, 2Centre for Discovery Brain Sciences, University of Edinburgh 30. Manipulating Microglia and Macrophage Phenotype to Improve Outcome after Intracerebral Haemorrhage Caoimhe Kirby, Josef Priller, Rustam Al-Shahi Salman, Colin Smith, Barry McColl 1Centre for Discovery Brain Sciences, 2Centre for Clinical Brain Sciences, 3UK Dementia Research Institute, University of Edinburgh 31. Nrf2 induction in myeloid cells is neuroprotective after intracerebral haemorrhage James Loan,1,2,3,4 Caoimhe Kirby,1,2,3 Rustam Al-Shahi Salman,2,4 Barry McColl,1,3 Giles Hardingham1,3 1Centre for Discovery Brain Sciences, 2Centre for Clinical Brain Sciences, 3UK Dementia Research Institute, University of Edinburgh, 4Department of Clinical Neurosciences, NHS Lothian 32. Endothelial dysfunction in a novel rat model of small vessel disease Sophie Quick, Rikesh Rajani, Anna Williams MRC Centre for Regenerative Medicine, University of Edinburgh

Cognition

33. AppNL-G-F/NL-G-F mice show impaired behavioural tagging but intact object recognition memory in middle adulthood Tabitha Broadbelt, Daniel Carnicero Senabre, Menekse Mutlu-Smith and Szu-Han Wang Centre for Clinical Brain Sciences, University of Edinburgh 34. Improving memory persistence: a behaviour tagging mechanism through the synergy of Ach and 5HT receptors. Menekse Mutlu-Smith, Rodrigo Leiva Penaloza and Dr. Szu-Han Wang Centre for Clinical Brain Sciences, University of Edinburgh 35. Executive functions in children with ADHD and ADHD + ASD symptoms Mina Murat1, Emily McDougal2, Jessica Oldridge2, Tracy Stewart2, Josie Booth2, Robert McIntosh1, Sinead Rhodes2 1Psychology, School of Philosophy, Psychology and Language Sciences, 2Clinical Brain Sciences, University of Edinburgh 36. The Arthur's Seat Effect: Why living in the quiet leafy suburbs might be linked to care home entry in old age - A longitudinal analysis of the factors associated with receiving formal care for the elderly in Scotland D. Helen Corby1,2,3,4, Dawn Everington5,6, John M. Starr2,3, Chris Dibben1,4,5,6, 1Administrative Data Research Centre Scotland (ADRCS), 2Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), 3Alzheimer Scotland Dementia Research Centre (ASDRC), 4Scottish Centre for Administrative Data Research (SCADR), 5School of Geosciences, University of Edinburgh, 6Scottish Longitudinal Study (SLS) 37. The minimal exposure duration required for neural processing of faces and emotional expressions Renzo C. Lanfranco1, Andres Canales-Johnson2, Dalila Achoui3, Axel Cleeremans3, Hugh Rabagliati1, David Carmel1,4 1University of Edinburgh, 2University of Cambridge, 3Université Libre de Bruxelles, 4Victoria University of Wellington 38. A peripheral epigenetic signature of inflammation shows associations with global brain atrophy and cognitive ability Eleanor Conole1,2,3,4, Anna Stevenson1,4,5, Susana Munoz-Maniega2, María Valdés-Hernández2,3, Matthew Harris6, Veronique Miron7, Heather Whalley6, Mark Bastin2,3, Joanna Wardlaw3, Sarah Harris2, Riccardo Marioni1,2, Ian Deary2,4, Simon Cox2,4 1Centre for Genomic and Experimental Medicine, 2Department of Psychology, 3Centre for Clinical Brain Sciences, 4Lothian Birth Cohort, 5Centre for Discovery Brain Sciences and UK Dementia Research Institute, 6Division of Psychiatry, 7Queen’s Medical Research Institute, University of Edinburgh

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