In vivo mechanisms of neurotoxicity

Lead Research Organisation: MRC Toxicology Unit

Abstract

One of the greatest challenges in neuroscience, and to public health, is how to treat neurodegenerative diseases. These diseases involve the death of brain cells. When they are lost, the functions they control memory, movement and emotion are also irreversibly lost. In order to treat these disorders, we need to understand why brain cells degenerate and die. Most importantly, we need to understand the earliest stages of this process as this gives us the greatest chance of intervening to prevent cell death. I previously made a mouse model of prion disease in which early degeneration is reversible. In these mice, early structural changes in brain cells lead to changes in behaviour, memory and electrical signalling, very like early changes seen in human neurodegenerative disorders. Using either special genetic techniques we were able to reverse this process. The structural, behavioural and memory changes were all reversed and instead of dying, the mice recovered and lived a normal lifespan. We aim to understand the processes that control this recovery and use this to find targets for treating neurodegeneration.

Technical Summary

Neurodegenerative diseases, such as Alzheimers, Parkinsons, Huntingtons disease and amyotrophic lateral sclerosis, have enormous clinical and economic impact world wide. Irrespective of the final pattern of clinical symptoms, they all are caused by an irreversible loss of neurons, which cannot be cured. But before neuronal death, there are neuronal dysfunction and synaptic impairment, which potentially can be treated.||My background is in prion diseases, modelling these in transgenic mice to look at mechanisms of neurotoxicity and developing new therapeutic approaches. In particular, I focused on the changes of early prion neurotoxicity and recovery from it. This new programme uses mouse models to understand the early molecular events in prion and other neurodegenerative diseases, looking in parallel at potential therapeutic targets for prevention of neuronal dysfunction and death.||Our main aims are to:|1. Characterise pre-degenerative neuronal changes.|2. Understand what triggers ultimate commitment to death in a malfunctioning neuron.|3. Define the molecular targets and the temporal window for functional recovery.||Initially, these questions will be addressed using our established mouse model of prion disease where early pathology is associated with a pivotal point in neuronal survival/death, and there is potential for recovery. We will use molecular biological, biochemical and neurophysiological techniques, as well as neuronal imaging in culture and in vivo to characterise the underlying cellular and synaptic changes, including alterations in signalling pathways and ion channels.||The broader aims of the programme are:|4. to generate new mouse models to look at individual pathways implicated in early dysfunction and their effect on neuronal function and death.|5. to address therapeutic strategies for the treatment of neurodegeneration.

Publications

10 25 50
 
Description Chair, UK-India Joint Centre Partnerships Panel (MRC-DPT)
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
 
Description Expert advisor ERC H2020 FET-OPEN Research and Innovation Intiative
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
 
Description MRC Neuroscience strategy board
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description MRC's Genome Editing for Mice in Medicine Initiative
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Member of MRC Neuroscience and Mental Health Board
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description RSM clinical neuroscience council
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guidance committee
 
Description Scientific Advisory Board MRC Harwell
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Scientific Advisory Board for Wallenberg Center for Molecular Medicine
Geographic Reach Europe 
Policy Influence Type Participation in a advisory committee
 
Description Wellcome Trust Expert Review Group for Cell and Molecular Neuroscience
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description leicester neuroscience steering committee
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guidance committee
 
Description scientific review panel, Scientific Foundation of Ireland
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Alz Soc/ADDF Drug repuprosing
Amount £200,000 (GBP)
Funding ID 221 
Organisation Alzheimer's Society 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2015 
End 02/2017
 
Description CoEN
Amount £196,033 (GBP)
Funding ID MR/S00503X/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 05/2018 
End 04/2020
 
Description Collaborative Award in Science
Amount £1,877,553 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2021
 
Description Developing the repurposed neuroprotective drug trazodone for clinical trials
Amount £55,000 (GBP)
Organisation Medical Research Council (MRC) 
Department MRC Confidence in Concept Scheme
Sector Charity/Non Profit
Country United Kingdom
Start 01/2019 
End 09/2019
 
Description ERC consolidator award
Amount € 2,000,000 (EUR)
Funding ID UPR-­-Neuro 647479 
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 09/2015 
End 08/2020
 
Description Gnodde Goldman Sachs Translational Neuroscience Group
Amount £1,124,054 (GBP)
Organisation Goldman Sachs 
Department Goldman Sachs Gives UK
Sector Charity/Non Profit
Country United Kingdom
Start 01/2019 
End 01/2024
 
Description Identification of neurodegenerative stress response modulators in young and aged iNeurons Collaborators
Amount £555,000 (GBP)
Funding ID OTAR2-054 
Organisation The Wellcome Trust Sanger Institute 
Department Open Targets
Sector Academic/University
Country United Kingdom
Start 04/2018 
End 04/2021
 
Description Joint Programming in Neurodegenerative Diseases
Amount £348,913 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2018 
End 01/2021
 
Description MRC
Amount £250,000 (GBP)
Funding ID RG79399 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2015 
End 01/2018
 
Description MRC intramural programme funding
Amount £2,000,000 (GBP)
Organisation Medical Research Council (MRC) 
Department MRC Toxicology Unit
Sector Academic/University
Country United Kingdom
Start 04/2013 
End 03/2018
 
Description NEUROPRION Use of RNAi for treatment of inherited prion disease (14.4m euros across 41 participants)
Amount £90,000 (GBP)
Funding ID 506579 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 09/2007 
End 08/2009
 
Description consolidator award
Amount £1,800,000 (GBP)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 04/2016 
End 03/2021
 
Description experimental medicine grant
Amount £50,000 (GBP)
Organisation MRC Dementias Platform UK 
Sector Academic/University
Country United Kingdom
Start 07/2017 
End 06/2019
 
Title NFH-Cre/MloxP mice 
Description cre deleter mice in neurons floxed prp mice crossed led to adult onset knockout of prp in neurons 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2006 
Provided To Others? Yes  
Impact reversal prion disease widely used mouse model 
 
Description Altered mRNA translation as a pathogenic mechanism across ND 
Organisation Max Planck Society
Department Max Planck Institute for Brain Research
Country Germany 
Sector Academic/University 
PI Contribution Expertise in the field of neurodegeneration and the unfolded protein response
Collaborator Contribution Expertise in mRNA translation and neurodegenerative diseases
Impact None so far
Start Year 2018
 
Description Altered mRNA translation as a pathogenic mechanism across ND 
Organisation Max Planck Society
Department Max Planck Institute for Molecular Biomedicine
Country Germany 
Sector Academic/University 
PI Contribution Expertise in the field of neurodegeneration and the unfolded protein response
Collaborator Contribution Expertise in mRNA translation and neurodegenerative diseases
Impact None so far
Start Year 2018
 
Description Altered mRNA translation as a pathogenic mechanism across ND 
Organisation McGill University
Country Canada 
Sector Academic/University 
PI Contribution Expertise in the field of neurodegeneration and the unfolded protein response
Collaborator Contribution Expertise in mRNA translation and neurodegenerative diseases
Impact None so far
Start Year 2018
 
Description Altered mRNA translation as a pathogenic mechanism across ND 
Organisation National Institute of Health and Medical Research (INSERM)
Country France 
Sector Academic/University 
PI Contribution Expertise in the field of neurodegeneration and the unfolded protein response
Collaborator Contribution Expertise in mRNA translation and neurodegenerative diseases
Impact None so far
Start Year 2018
 
Description ISRIB-like substances 
Organisation AstraZeneca
Department MedImmune
Country United Kingdom 
Sector Private 
PI Contribution we will test neuroprotective effects of new compounds in mice
Collaborator Contribution generation of compounds in vitro testing
Impact none yet
Start Year 2016
 
Description ISRIB-like substances 
Organisation University of Cambridge
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution we will test neuroprotective effects of new compounds in mice
Collaborator Contribution generation of compounds in vitro testing
Impact none yet
Start Year 2016
 
Description Investigating chromatin landscapes in ND models 
Organisation German Centre for Neurodegenerative Diseases
Country Germany 
Sector Public 
PI Contribution Expertise in neurodegenerative models
Collaborator Contribution Expertise in chromatin remodelling and analysis
Impact None so far
Start Year 2018
 
Description Regulation of protein synthesis by elongation control in health and disease 
Organisation Beatson Institute for Cancer Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in protein synthesis regulation in neurodegenerative disease
Collaborator Contribution Expertise and resources in RNA biology, systems biology and cancer biology
Impact None so far
Start Year 2016
 
Description Regulation of protein synthesis by elongation control in health and disease 
Organisation Medical Research Council (MRC)
Department MRC Toxicology Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in protein synthesis regulation in neurodegenerative disease
Collaborator Contribution Expertise and resources in RNA biology, systems biology and cancer biology
Impact None so far
Start Year 2016
 
Description Regulation of protein synthesis by elongation control in health and disease 
Organisation University of Kent
Country United Kingdom 
Sector Academic/University 
PI Contribution Expertise in protein synthesis regulation in neurodegenerative disease
Collaborator Contribution Expertise and resources in RNA biology, systems biology and cancer biology
Impact None so far
Start Year 2016
 
Description Single molecule imaging of synaptic protein dynamics in neurodegeneration 
Organisation University of Kyoto
Department Institute of Integrated Cell Material Sciences
Country Japan 
Sector Academic/University 
PI Contribution Structural synaptic plasticity analysis in primary neuronal cultures of wild type and neurodegenerative disease mouse models
Collaborator Contribution Single-molecule imaging and super-resolution imaging o synaptic plasticity in primary neuronal cultures of wild type and neurodegenerative disease mouse models
Impact none yet
Start Year 2014
 
Description pharmacokinetic studies on PERK inhibitors 
Organisation GlaxoSmithKline (GSK)
Department GSK Oncology
Country United Kingdom 
Sector Private 
PI Contribution mechanism of neurodegeneration in prion disease and use of compounds to modulate disease progression
Collaborator Contribution PK and PD analyses GSK supplied compounds LC/MS-MS Compound production
Impact Oral treatment targeting the unfolded protein response prevents prion neurodegeneration and clinical disease in mice. Moreno JA, Halliday M, Molloy C, Axten JM, Willis AE, Ortori CA, Barrett DA, Fischer PM and Mallucci GR. Science Translational Medicine, 2013, 5,206ra138. Sustained translational repression by eIF2a-P mediates prion neurodegeneration. Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Guerra Martin M, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, M Bushell and Mallucci GR*. Nature 2012, 485, 507-11
Start Year 2012
 
Description pharmacokinetic studies on PERK inhibitors 
Organisation University of Cambridge
Department Cambridge Institute for Medical Research (CIMR)
Country United Kingdom 
Sector Academic/University 
PI Contribution mechanism of neurodegeneration in prion disease and use of compounds to modulate disease progression
Collaborator Contribution PK and PD analyses GSK supplied compounds LC/MS-MS Compound production
Impact Oral treatment targeting the unfolded protein response prevents prion neurodegeneration and clinical disease in mice. Moreno JA, Halliday M, Molloy C, Axten JM, Willis AE, Ortori CA, Barrett DA, Fischer PM and Mallucci GR. Science Translational Medicine, 2013, 5,206ra138. Sustained translational repression by eIF2a-P mediates prion neurodegeneration. Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Guerra Martin M, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, M Bushell and Mallucci GR*. Nature 2012, 485, 507-11
Start Year 2012
 
Description pharmacokinetic studies on PERK inhibitors 
Organisation University of Nottingham
Department Medicinal and Biological Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution mechanism of neurodegeneration in prion disease and use of compounds to modulate disease progression
Collaborator Contribution PK and PD analyses GSK supplied compounds LC/MS-MS Compound production
Impact Oral treatment targeting the unfolded protein response prevents prion neurodegeneration and clinical disease in mice. Moreno JA, Halliday M, Molloy C, Axten JM, Willis AE, Ortori CA, Barrett DA, Fischer PM and Mallucci GR. Science Translational Medicine, 2013, 5,206ra138. Sustained translational repression by eIF2a-P mediates prion neurodegeneration. Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Guerra Martin M, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, M Bushell and Mallucci GR*. Nature 2012, 485, 507-11
Start Year 2012
 
Description pharmacokinetic studies on PERK inhibitors 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution mechanism of neurodegeneration in prion disease and use of compounds to modulate disease progression
Collaborator Contribution PK and PD analyses GSK supplied compounds LC/MS-MS Compound production
Impact Oral treatment targeting the unfolded protein response prevents prion neurodegeneration and clinical disease in mice. Moreno JA, Halliday M, Molloy C, Axten JM, Willis AE, Ortori CA, Barrett DA, Fischer PM and Mallucci GR. Science Translational Medicine, 2013, 5,206ra138. Sustained translational repression by eIF2a-P mediates prion neurodegeneration. Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Guerra Martin M, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, M Bushell and Mallucci GR*. Nature 2012, 485, 507-11
Start Year 2012
 
Description 10th UK-Korea Neuroscience Symposium, The Royal Society, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This talk will summarise my lab's recent progress in understanding mechanisms of neurodegeneration and how this is informing new therapeutic approaches. The central concept is the identification of common pathways across the spectrum of these disorders (which include Alzheimer's and related diseases) relevant for both mechanistic insights and therapy. These include both 'toxic' processes that can be targeted to prevent neuronal death, and regenerative processes that can be harnessed for repair. I will briefly present data from mouse models targeting both of these aspects and their relevance for human disease. I will focus on modulating the Unfolded Protein Response pharmacologically, including and the recent discovery of repurposed drugs ready for clinical trials. I will also touch on the strategy of harnessing pathways that drive synapse regeneration, as occurs in hibernation, for the therapy of neurodegenerative disease.
Year(s) Of Engagement Activity 2017
 
Description 2017 ISN-ESN MEETING, Paris 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Professor Giovanna Mallucci delivered the PL05 Plenary Lecture 5 Neurodegeneration: from Molecules to Medicines
The aim of the International Society for Neurochemistry is to facilitate the worldwide advancement of neurochemistry and related neuroscience disciplines, to foster the education and development of neuroscientists, particularly of young and emerging investigators and to disseminate information about neurochemistry and neurochemists' activities throughout the world.
Year(s) Of Engagement Activity 2017
URL https://www.neurochemistry.org/wp-content/uploads/2018/10/Final-Program-Book-2017_ISN-ESN-Meeting-Pr...
 
Description 27th Annual Meeting of the Network for European CNS Transplantation & Restoration (NECTAR), Dublin 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Definite increased interest from the students/patients at the conference as the following tweets show:

Tour de force from Giovanna Mallucci from the Dementia Research Institute on pharmacological approaches to prion disease and neurodegeneration. Outstanding data and superb speaker.

Wow! #NECTAR2017 - What an epic rollercoaster ride of a conference! We cannot thank you all enough for making it so great. The science, the emotion, the tears and all of the Tweets.

Sitting in at @NECTAR_EU Conference in Malahide, Dublin for the past few days. I won't lie, this stuff is way over my head but these guys at #NECTAR2017 are rooting for me and everyone with #Parkinsons and I'm eternally grateful

Back in the lab. Those stem cells won't grow themselves! #teamdowd #NECTAR2017 #WomenInSTEM
Year(s) Of Engagement Activity 2017
 
Description 28th Cambridge Festival of Neuroscience Keynote lecture "The treatment of dementia: new directions", Cambridge, UK, March 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Public lecture: 28th Cambridge Festival of Neuroscience: "The treatment of dementia: new directions", Cambridge, UK, March 2016
Year(s) Of Engagement Activity 2016
 
Description 2nd Molecular Biology of Ageing Meeting 2017, The Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk on Manipulating the Unfolded Protein Response for treatment of neurodegeneration
Year(s) Of Engagement Activity 2017
 
Description 48th Annual Meeting of American Society for Neurochemistry, Little Rock, Arkansas, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk on ER Stress and Neurodegeneration Symposium.

Outline: four days of symposia and colloquia designed to address the four major themes of our Society: 1) Building the Nervous System; 2) Glial Cell Biology; 3) Molecular and Cell Biology of the Nervous System, and 4) Neurodegeneration and Disease. World-class plenary speakers will include Drs. Carol Colton, Rachel Wong, Marc Freeman and Zhigang He. An important component at ASN meetings is the engagement of our society with trainees, therefore special efforts have been taken to encourage young investigator participation. This includes daily poster sessions, short oral presentations selected from submitted abstracts, trainee lunches with plenary speakers, and numerous travel awards.
Year(s) Of Engagement Activity 2017
URL https://www.allcongress.com/medical-congress/48th-annual-american-society-for-neurochemistry-asn-mee...
 
Description 6th European Synapse Meeting, Milan 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The aim of this meeting is to bring together junior and senior neuroscientists working on synapses and to provide a forum for new directions and ideas in synapse research. This serves to create a European research community with an active role in promoting synaptic research and its funding within the EU. The meeting welcomes participation from all neuroscientists within and outside the EU.
Year(s) Of Engagement Activity 2017
URL https://www.fens.org/News-Activities/Calendar/Meetings/2017/12/6th-EUROPEAN-SYNAPSE-MEETING/
 
Description 7th Optic Nerve Meeting, Obergurgl, Austria 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Intended for basic scientists and clinicians to address important topics in translational research, including scientists in interdisciplinary areas such as neurology, neurodegenerations and autoimmunity
Year(s) Of Engagement Activity 2017
URL http://www.optic-nerve-online.com/images/Agenda/2017OpticNerveMeeting_FinalAgenda.pdf
 
Description Alzheimer's Research UK Conference 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact tba
Year(s) Of Engagement Activity 2017
 
Description Anne Silk Lecturer, Royal Society of Medicine, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact public lecture on progress in treatment of neurodegeneration
Year(s) Of Engagement Activity 2014
URL https://www.rsm.ac.uk/events/events-listing/2013-2014/groups/public-engagement-programme/pee07-anne-...
 
Description BBC radio interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact naked scientist radio interview about hibernation and Alzheimer's
Year(s) Of Engagement Activity 2016
URL http://www.thenakedscientists.com/HTML/podcasts/naked-scientists/show/20160119/
 
Description Clinician Scientist Symposium on Translational Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Giovanna Mallucci was invited to present the keynote lecture.
This is a two-day Clinician Scientist Symposium on Translational Medicine is held in Berlin every two years. The Clinician Scientists can invite internationally renowned physicians and researchers to attend the event as speakers and this means the Clinician Scientists can discuss their project in person with leading figures in their own research field. The Clinician Scientists also have the opportunity to present their research during the symposium (in the form of a short talk or poster presentation).

.
Year(s) Of Engagement Activity 2018
 
Description ELSC conference 7 Cellular and Molecular Neuroscience: From Generation to Degeneration 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Israeli Society for Developmental Biology (IsSDB) was established to promote the study and scientific excellence of research in the area of developmental biology in Israel. The IsSDB offers Israeli developmental biologists a framework for scientific interactions and the exchange of information within Israel and internationally. The IsSDB is also representing the developmental biology community in Israel in front of other national and international organizations.
Year(s) Of Engagement Activity 2017
URL http://issdb.org/event/elsc-conference-7-cellular-and-molecular-neuroscience-from-generation-to-dege...
 
Description East midlands medical student conference: Keynote 'INSPIRE' lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact unknown
Year(s) Of Engagement Activity 2014
 
Description Ecole Neuroscience de Paris 10 year anniversary symposium, Paris, France 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact During the 2017 ENP Days, members of the network and their international guests celebrated the 10th anniversary of the Ecole des Neurosciences de Paris.
Let us recall that the ENP was initiated by Dr Jean-Antoine Girault (Institut du Fer Moulin), and established in 2007 as a "Réseau Thématique de Recherche Avancée" by the Ministry of Research and Education. Acting since 2011 as a private foundation, it is now managed by a Steering Committee of twelve researchers headed by Dr Serge Charpak, a Board of Trustees presided by Alain Bravo, and a Scientific Advisory Board composed by nine eminent scientists.
All gathered at the Collège des Bernardins, a magnificent cistercian building located in the heart of Paris, during two days and nights of science and conviviality.
After the first exciting conference given by Dr Thomas Mrsic-Flogel (Uni. Basel), a poster and cocktail session opened the retreat on Wednesday night. It was also the occasion for ENP GP 2017 candidates to mingle with ENP students, postdocs from ENP teams, PhD guests from the GSN program in Munich and the 2016-17 interns from Chile. Grant holders from the Domain d'Intérêt Majeur de la Région Ile de France ?Cerveau et Pensée were also invited to the retreat, and some young scientists got the chance to present their work to the community. A dozen ENP teams also presented posters so that candidates and peers could learn about on ongoing research projects and initiate future collaborations.
Year(s) Of Engagement Activity 2017
URL https://nis.nikonimagespace.com/html/guest/en/index.html?g=zlZdQTCNgbYttlYM9n22PXlfolefe_KPoAnLYAtH8...
 
Description Frank May Medal for Excellence in Research and Outstanding Future Promise; University of Leicester, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact public lecture discussing medical advances
Year(s) Of Engagement Activity 2012
 
Description From synapses to memory: RNA based regulatory mechanisms 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The meeting aimed to bring together leading investigators and young scientists from the field. These investigators employ a wide range of techniques such as computational modeling, genome-wide sequencing, genetic manipulation and cellular imaging. They discussed fundamental aspects of RNA based regulation of memory formation and its alterations in neurodevelopmental disorders associated with memory dysfunction. This meeting will be a platform for stimulating informal yet intense discussions and also foster active collaboration that will certainly take this field into a new direction.

Professor Mallucci delivered the Keynote Lecture entitled "Cooling synapses: RNA chaperones and neuroprotection"
Year(s) Of Engagement Activity 2018
 
Description Futures Congress in Santiago de Chile 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Invited by Senator Girardi, President of the Senate's Future Challenges, Science, Technology and Innovation Commission in Chile, to participate as a Guest Speaker in the VIII Futures Congress (Congreso Futuro in Spanish), "a global flagship knowledge engagement event set to take place between the 14th-20th January 2019". Since the establishment of the Futures Congress in 2011, it has become a major forum in Latin America for addressing the many challenges that humanity is faced with and brings together scientists and humanists to discuss how we can achieve a better future.
Congreso Futuro is unique in the region for providing Nobel laureates, scientists, researchers, artists, opinion leaders and citizens alike "the opportunity to experience some of the world's most cutting-edge research, participate in the understanding of emerging trends and actively engage in the innovation of ideas and debates that directly influence the globe."
Approximately 40,000 people directly attended events of last year's Congreso Futuro around the country. The talks are live-streamed and covered on national TV.
Year(s) Of Engagement Activity 2019
 
Description MRC PEN event 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact public panel debate between writers and scientists " barriers to creativity"
Royal geographical society
public debate and questions

MRC website
PEN website
Year(s) Of Engagement Activity 2009
 
Description Media interviews for STM paper 2013 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact MRC scientists halt neurodegeneration in mice (BBC 4 Today programme, 07.12) also interviews on BBC, ITV, Channel 5, Sky, CNN, ABC, Al jazeera, local radio-stations
The Independent (front page) with additional online commentary
The Daily Express (front page)
Daily Mirror (front page)
The Sun (page 4) Online version unavailable
Daily Mail (page 5)
The Guardian (page 6)
The Daily Record (page 5)
The Scotsman p13
The Herald p5 Online version unavailable
BBC online
ITV
Sky News
Channel 4
The Daily Telegraph (page 14)

The story was also reported without an MRC mention in The Times (front page, online version unavailable)

Plus...innumerable regional newspapers, radio and TV outlets - particularly in the Leicester area!! - and international outlets from CNN to ABC to The Times of India, Time magazine, Spanish, Italian, Brazilian, Polish, Turkish, French and German outlets.
A pill for neurodegenerative disease? Not yet, but we're getting closer (BBC News Online)
The Guardian
SKY News
BBC World Service
ITV
BBC World Business Report
Radio 5
BBC Breakfast

The Daily Mirror (page 8) highlighted the research and asked what other diseases can we hope to defeat. Online version unavailable
The Sunday Times, News Review page 2, Vivienne Parry
(BBC News Online) The Guardian
SKY News
BBC World Service
ITV
BBC World Business Report
Radio 5

The Daily Mirror (page 8) highlighted the research and asked what other diseases can we hope to defeat. Online version unavailable
The Sunday Times, News Review page 2, Vivienne Parry

Huge interest into the Unit's research
Year(s) Of Engagement Activity 2013,2014
 
Description Nature podcast 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact nature podcast about discovery of hibernation and synaptic regeneration and role in neuroprotection
Year(s) Of Engagement Activity 2015
URL http://www.nature.com/nature/podcast/index-2015-01-15.html
 
Description Neurodegenerative Diseases: Biology & Therapeutics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A primary goal of the meeting is to provide a forum where medical scientists from academia can interact with scientists from the biopharmaceutical industry, thus forging a community of academic and industry researchers who recognize that they have much to learn from each other. Rational drug discovery for neurodegenerative diseases has begun to yield compounds and treatments that are now entering clinical settings. For human studies utilizing these compounds and treatments to be maximally informative, it is crucial that scientists from academia and industry meet regularly to exchange data and ideas.

Professor Mallucci delivered a talk on: UPR activation in astrocytes induces non-cell autonomous neurotoxicity in neurodegenerative disease.
Year(s) Of Engagement Activity 2018
URL https://meetings.cshl.edu/meetings.aspx?meet=DEGEN&year=18
 
Description PRION 2017 Deciphering Neurodegenerative Disorders 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact These meetings are attended by people from many countries and many different disciplines such as: protein chemistry, genetics, clinical neurology, epidemiology, public health and agriculture/animal medicine. This year, there were around 350 attendees and, most importantly, members of the CJD International Alliance were there to present the human side of the story. This presentation from the patient/family point of view is always greatly appreciated by the researchers and helps to give additional motivation to their work in understanding these diseases. Those who are personally affected by CJD should take heart that there is such a concerted international effort in this difficult area.

The meeting's subtitle reflected the growing interest in the relationship between prion diseases (including CJD) and other, more common, illnesses such as Alzheimer's Disease, Parkinson's Disease and Motor Neuron Disease. Whatever the differences between these diseases (in why they occur and how they affect people), they all have a particular kind of disease feature called 'neurodegeneration'. This is difficult to define succinctly but, in essence, in a neurodegenerative disease, particular groups of neurons (nerve cells) dysfunction and die associated with the tissue deposition of abnormally folded protein (in the case of prion disease, it is the prion protein). Researchers into these different diseases are, increasingly, looking to see how their knowledge may be helpful to each other.
Year(s) Of Engagement Activity 2017
 
Description Pamela MacKinnon Lecture: St Hilda's Medical Society Conference, "The Road to New Dementia Treatments" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact St Hilda's Medical Society Conference, 'Depths of the Mind: Exploring Issues in Mental Health', was a very warm reunion for our alumnae and alumni who read Medicine and Experimental Psychology and also current students and recent graduates.
Professor Giovanna Mallucci, Department of Clinical Neurosciences and Associate Director of the UK Dementia Research Institute at the University of Cambridge, gave the Pamela MacKinnon Lecture: The Road to New Dementia Treatments. Our alumna, Professor Mallucci, spoke of how her career had been inspired by Pamela MacKinnon and our Emeritus Fellow, Professor Jane Mellanby, who introduced her. Professor Mallucci shared groundbreaking research with the potential to lead to treatments to delay neuronal loss, which would allow people to stay at home for longer and help them to have meaningful lives.
Year(s) Of Engagement Activity 2018
URL https://www.sthildas.ox.ac.uk/sites/www.st-hildas.ox.ac.uk/files/Medical%20Society%20Conference%2020...
 
Description Plenary speaker and panelist at International Monetary Fund First TalentNomics Conference: Innovation, Economic Growth, and the Empowerment of Women, Washington DC, USA, November 2015. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Plenary speaker and panelist at International Monetary Fund First TalentNomics Conference: Innovation, Economic Growth, and the Empowerment of Women, Washington DC, USA, November 2015.
Year(s) Of Engagement Activity 2015
 
Description ST HILDA'S MEDICAL SOCIETY CONFERENCE 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Talk at St Hilda's Medical Society Conference - Depths of the Mind: Issue in Mental Health - to alumnae and alumni who read Medicine and Experimental Psychology and also current students and recent graduates
Year(s) Of Engagement Activity 2018
 
Description Science Festival in Genova 2012 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact public interest high

public interest
Year(s) Of Engagement Activity 2012
 
Description Speaker at Cambridge Alumni Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Speaker at UofC Alumni Festival. title: the road to new dementia treatments
Year(s) Of Engagement Activity 2017
 
Description Television interviews 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact discussed our research which was hailed as "turning point in search for medicines to control and prevent Alzheimer's"
Year(s) Of Engagement Activity 2013
URL http://www.bbc.co.uk/news/health-24462699.
 
Description The 2017 UCD Conway Festival of Research & Innovation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact Below is a media report from the Conference which shows that (1) Giovanna Mallucci was THE presenter worth mentioning and (2) is able to instil major interest in her field.

"The 2017 UCD Conway Festival of Research & Innovation got under way last week with lectures and presentations by leading scientists from varied fields.
The festival, now in its seventeenth year, serves to highlight the substantial scientific research and innovation achievements being undertaken by the scientists and researchers of the UCD Conway Institute of Biomolecular and Biomedical Research. The annual event aims to celebrate the work that is going on at the moment with lectures from scientists from industry, academia, and clinical settings complemented with scientific talks, poster presentations and a career discussion forum for budding researchers.
"It's about linking ideas, linking people, getting discussions going and starting new collaborations" -

Topics covered ranged from cell signalling, cancer cell state maintenance, neurodegeneration, yeast evolution, comparative and integrative genomics, obesity, and botany.
Giovanna Mallucci from the Department of Clinical Neurosciences at Cambridge University gave superb insight into the mechanisms and possible treatment in neurodegenerative diseases in her lecture, 'Neurodegeneration: from molecules to medicines'. In her talk, Mallucci expressed how the combination of a decrease in synapse number and increase in the accumulation of misfolded proteins lead to neuronal loss."
Orla Daly - Science Editor
Year(s) Of Engagement Activity 2016,2017
 
Description The Edinburgh Parkinson's Lecture 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Guest Lecture: The Road to New Treatments for Dementia and Parkinson's

An audience of around 200 people, predominantly members of the Edinburgh Branch of Parkinson's UK, but including also many health professionals and researchers, came to the Queens Medical Research Institute, University of Edinburgh, to hear Giovanna Mallucci deliver the seventh annual Edinburgh Parkinson's Lecture.

Professor Mallucci answered questions from the audience, in a lively session chaired by Dr Conor Maguire. Themes included the importance of sleep in the maintenance of synaptic health and repair; the desirability of early intervention, although more will be known when clinical trials are underway about whether it is ever too late for treatment; the role of exercise in boosting synapses; and optimism about the future as new ways of slowing progress of dementia and Parkinson's are developed.
Year(s) Of Engagement Activity 2018
URL https://www.edinburghparkinsons.org/wp-content/uploads/2018/09/Mallucci-lecture-2018-1.pdf
 
Description The Scripps Research Institute, Neuroscience Seminar Series, University of California 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Scripps Research ranks as the most influential scientific organization in the world, unparalleled in propelling innovation in science and medicine. Their unique structure merges foundational studies in biology, chemistry and computer science with translational science to produce the next generation of drugs and advances in digital and precision medicine. Scientists in the institute's five academic research departments work hand-in-hand with researchers of the Scripps Research Translational Institute and Calibr. The neuroscience seminar series is designed to expose the graduate students to invited experts in their field from around the world to cultivate the next generation of scientific leaders and expand the frontiers of knowledge to drive innovation that improves lives around the planet.
Year(s) Of Engagement Activity 2019
 
Description Translating Translation: From Basic Mechanisms to Molecular Medicine - 38th Blankenese Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Blankenese Conference focused on basic molecular mechanisms of mRNA translation will be brought together with those who study diseases where effects on translation are prominent. Its goal is to foster discussions between these groups. It will provide a perfect forum for advanced scientific exchange in these interconnected areas
Year(s) Of Engagement Activity 2018
 
Description UK Conference of Science Journalists 2012 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact dialogue with science writers

interest in science reporting
Year(s) Of Engagement Activity 2012
 
Description Unit Open Day 2013 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Over 500 members of the public visited the Unit

Members of the public were very appreciative.
Students asked to come and carry out work experience in the Unit.
Year(s) Of Engagement Activity 2013
URL http://tox.mrc.ac.uk/
 
Description Wellcome Genome Advance Scientific Course on Molecular Neurodegneration 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Lecture on Neurodegeneration: from molecules to medicines as part of the Wellcome Genome Campus Advance Scientific Course on Molecular Neurodegneration
Year(s) Of Engagement Activity 2017
 
Description biology in action 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Biology in Action is a very popular annual day, which sets out to give students a stimulating day of biology in five wide-ranging sessions, and helps them and their teachers keep up to date with developments and issues. We aim to provide students with inspiration to pursue their studies at a higher level through talks that go beyond the curriculum.
Year(s) Of Engagement Activity 2016
 
Description media interviews 2007 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact numerous interviews to BBC radio, US radio
science press
national press

widespread reporting in science and mass media
radio 4 interview 'science now'
Year(s) Of Engagement Activity 2007
 
Description mrc annual report 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact interviewed as one of MRC's 'people behind discovery'

positive feedback, applicants to work with me
Year(s) Of Engagement Activity 2007
 
Description nottingham inspire 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact 400 medical students
careers in science and medicine
Year(s) Of Engagement Activity 2014
 
Description nottingham inspire 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact 400 medical students
careers in science and medicine
Year(s) Of Engagement Activity 2014
 
Description press interviews 2008 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact press interviews broadsheets science journals BBC Radio 4 science now

widespread dissemination of research
Year(s) Of Engagement Activity 2008
 
Description radio interview 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact http://www.thenakedscientists.com/HTML/podcasts/naked-scientists/show/20160119/
Year(s) Of Engagement Activity 2016
URL http://www.thenakedscientists.com/HTML/podcasts/naked-scientists/show/20160119/
 
Description schools careers in science talks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Schools
Results and Impact pupils interested in science
work experience in my lab

work experience and science interests
Year(s) Of Engagement Activity 2010,2011,2012
 
Description toxicology open day 2010 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact presentation to graduate students

top performer voted by students!
Year(s) Of Engagement Activity 2010
 
Description work experience 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Schools
Results and Impact work student for 1 week in my lab
work experience undergraduate for 10wks

positive experience further applicants
Year(s) Of Engagement Activity 2010,2012,2013,2014
 
Description work highlighted British Neuroscience Bulletin 2012 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact highlight of groups reseracj

generated much interest adn phd applications
Year(s) Of Engagement Activity 2012