20 1 9 REPORT - Institut Pasteur de Lille
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20 REPORT 19 P R I VAT E N O N - P R O F I T F O U N D AT I O N S I N C E 1 8 9 8 www.pa steur-lille.fr
THE EDIT IN 2019, OUR FOUNDATION CELEBRATED THE 120TH ANNIVERSARY OF THE OPENING OF ITS HISTORIC BUILDING! 120 years of innovation, research and fighting and Higher Education (HCERES) highlighted disease. 120 years of commitment and joint the excellence of the teams and the quality action. 120 years at the service of everyone's of the research carried out on the campus. health. And, above all, 120 years of loyalty to the In association with our partners – CNRS, ideas of Pasteur and the wishes of the pioneers INSERM, Lille university hospital, University of of the institute: Pasteur, Calmette, Guérin. Lille – the 8 mixed research units are therefore developing their projects and organisation 2 It is this history, peppered with doubts, around the longevity project, which is the efforts, major discoveries and successes major objective of our foundation. Thanks to that provides the foundation on which the the renewed support of the French Ministry future of Institut Pasteur de Lille is being built of Research, we can continue our projects through its strategic project. on the issue of longevity and bear witness to the scientific standards of our foundation, The evaluation of the research teams by the confirmed by the 365 scientific publications High Council for the Evaluation of Research of the research teams. ED ITO-
Convinced of the key importance of prevention would not be possible without the strong in improving health, the teams at the Centre and ongoing support of the donors, patrons for Health and Longevity has developed new and companies that I would like to thank very offers in 2019 for businesses and individuals. warmly on behalf of all the researchers. Through vaccination, the Longevity Course, health coaching, clinical studies and training, Together, let’s speed up research and take the disease prevention efforts are tackled action to promote tomorrow’s health. on a cross-sector basis and must respond to 3 the challenges of our society. As a result, the Many thanks for your commitment alongside collaboration with associations and healthcare our teams. agents promotes and enhances our actions in the service of healthcare. All these advances in healthcare, all these innovations, all these fights against disease Prof. Xavier Nassif Managing director
CONTENTS 6 8 20 42 4 52 60 70 2019 ACTIVITY REPORT Design and production: Communications and sponsorship department - Institut Pasteur de Lille, Karbone14, Cam&Lou Photo credits: ©Institut Pasteur de Lille photo library - ©Les Yeux d'Argos - ©Nikkovp - ©Renaud wailliez - ©La Voix du Nord 74 ©Barbara Grossmann - ©Joaquim Dassonville Collectif DR - ©freepik.com - Adobe Stock: ©Marzanna Syncerz, ©rogerphoto, ©Darren Baker, ©agenturfotografin, ©WavebreakmediaMicro, ©science photo - Unsplash.com: ©auremar - ©katemangostar
HIGHLIGHTS LO N G E V I T Y O B J E C T I V E Speeding up research and acting for better health tomorrow The strategic project of Institut Pasteur de Lille International relations Results from the 3rd CPER-CTRL call for projects Launch of the 4th CPER-CTRL call for projects (phase 4) S P E E D I N G U P R E S E A R C H F O R B E T T E R H E A LT H TO M O R R OW LONGEVITY: interdisciplinary teams for excellence in research The Campus Research Teams Technology platforms Biotechs P R E V E N T TO DAY I N O R D E R TO AG E W E L L TO M O R R OW Centre for Health and Longevity: Innovation for Ageing Well Health checks and educational activities 5 Research within the Centre for Health and Longevity Nutrition and Physical Activity Department The International Vaccination centre Development unit Microbiological Safety Unit S U P P O R T T H E F O U N DAT I O N , A DVA N C E TO G E T H E R ! Institut Pasteur members working together! Donations, legacies and solidarity events Business patronage The Institut Pasteur de Lille museum B U I L D TO M O R R OW ’ S F O U N DAT I O N A Foundation at the service of the population Institut Pasteur core values Our CSR Commitments The Executive Board Scientific and Administrative Organisational Chart Employment/Resources S C I E N T I F I C PA P E R S PA R T N E R S A N D S U P P O R T
KEY EVENTS 2019 2019: 120 YEARS OF RESEARCH AND INNOVATION 1894 At the end of the 19th century, three 1898 The Foundation is a non-profit organisation, quarters of the planet were decimated by infectious which is legally and financially independent of the diseases such as diphtheria, tuberculosis, cholera, Institut Pasteur in Paris. smallpox and rabies. The Nord-Pas de Calais region was not spared and the city of Lille had to face a 9 APR 1899 Institut Pasteur de Lille major diphtheria epidemic. Doctor Emile Roux, formally opened at its current premises on who studied the disease with Louis Pasteur in Paris, Boulevard Louis XIV, on the same day as the discovered the toxin responsible for diphtheria. statue of Louis Pasteur was unveiled on Place The decision to create the institute was approved Philippe Lebon. This great day was conducted in by the municipal council of 9 November 1894. the presence of ministers, official representatives Albert Calmette flew to Lille. An initial temporary of the French Academy, the Academy of Sciences laboratory was created at the Halle aux Sucres in and Medicine and Mrs Pasteur, without her the Vieux-Lille. The production of the diphtheria husband, who had sadly died 4 years earlier. serum could begin. This is how the history of Institut Pasteur de Lille began, 20 NOV 1895 The first stone of the originating in discoveries that would be significant building is placed in the heart of the Saint-Sauveur for Humanity, following in the footsteps of Louis district. Pasteur and the example initiated by Albert Calmette. 6 1899 2019
INSTITUT PASTEUR DE LILLE, FROM ITS FOUNDATION TO TODAY 2000 1894 evelopment of the activities of D the UMR1011 laboratory towards 2005 Creation of Institut Pasteur de Lille metabolic diseases to r esolve a diphtheria epidemic 1898 New nuclear receptors such as FXR and LXR at the heart of The Foundation was recognised as Method for identifying a latent tuberculosis infection pathophysiological processes a non-profit organisation of public leading to cardio-metabolic 9 APR 1899 interest by presidential decree diseases such as obesity, diabetes and its cardiovascular Opening of Institut Pasteur de Lille and unveiling of the statue of Louis 1901 2006 complications The beginnings of the study of Opening of the Émile Roux evelopment D of a nasal chronobiology in Lille Pasteur. In the presence of Albert dispensary, the first French whooping cough vaccine, which Identification of the nuclear re- Calmette, his wife, Mrs Pasteur, his preventorium for the prevention can be used for inoculation from ceptor Rev-erbα as a target of children and grandchildren of tuberculosis birth PPARα Discovery of the first genes involved in severe infantile 1904 Opening of the first biological 1921 2007 water purification station in La Madeleine, with a purification Discovery of the vaccine against tuberculosis: BCG (Bacillus 2009 Identification of a new gene that process applied by reation of EGID (European C may cause type 2 diabetes Calmette and Guérin) Albert Calmette Genomic Institute for Diabetes), the first research institute in France dedicated specifically to 1945 diabetes and its complications Identification of the genetic Creation of the regional blood transfusion centre 1948 determinants involved in 13% of the forms of Alzheimer's di- 2010 First international BCG congress sease Discovery of a biological marker at Institut Pasteur in Lille of heart failure, which can be used to identify the risk by way of a simple blood test 1951 2011 Implementation of the FROM 1966 TO 1970 Identification of five new factors international vaccination centre intended for travellers, and Launch of a tuberculosis prevention campaign in the of genetic susceptibility to Al- zheimer's disease 2012 approved by the WHO Sequencing in record time of Involvement of rare mutations mining area where 200,000 the Escherichia coli bacteria in common forms of type 2 children and adolescents were 1975 responsible for food poisoning diabetes and obesity screened and vaccinated with BCG Certification of the programme Installation of the Immunology and on tumour dormancy by the Parasitic Biology Department 1979 National Cancer Institute Equipex and Labex certification Identification and characterisation of the work of researchers of Lille 7 2013 of new oncogenes and their 1981 involvement in cancer Identification of genes involved Creation of the health in the resistance of tuberculosis 1984 examination centre Installation of the Jean-Charles 2015 Fruchart laboratory: First team reation of "Centre Transdis- C from Institut Pasteur de Lille to 2016 ciplinaire de Recherche sur la Longévité" 1985 take an interest in cardiovascular and metabolic diseases ignature of a framework S Creation of METIS: a website agreement for an with health recommendations for Creation of a nutrition department interdisciplinary partnership on international travellers digital sciences and health with 1986 the INRIA A new biological stethoscope Launch of a new research for heart disease 1994 objective on infection by the AIDS virus (HIV) and on the immune response against the regulatory Creation of the first mathemati- cal model to understand how the 2017 Installation of a new team that liver clock synchronises with the Installation of Eurabio/Synlab, will work on the nuclear recep- proteins of the virus in particular rhythm of meals a medical biology laboratory, on tors as therapeutic targets the Pasteur Lille campus Creation of the high-field Tuberculosis and resistance to Nuclear Magnetic Resonance 1996 antibiotics: discovery of a new (NMR) centre Elucidation of the action 2018 SMART-420 Heart surgery: Lille-based re- mechanisms of PPARα reation of the Institute of C he discovery of a new gene T searchers discovered the impact dependent fibrates on Biology of Lille (IBL) on the responsible for childhood of the time of day on the risk of lipoprotein metabolism Pasteur Lille campus obesity heart complications Discovery of a genetic marker Discovery of a biomarker for Test-tubes containing the original An edible mushroom that is pro- for diagnosing Alzheimer's di- lung, stomach and liver tumours, strains of the vaccine against mising for the fight against hu- sease and leukaemia tuberculosis (BCG) to be opened man genetic diseases Discovery of two protective ge- at Institut Pasteur de Lille Creation of the Centre for Health nes againstatherosclerosis Design of a new algorithm and Longevity for detecting the resistance of tuberculosis strains which are not 1997 1998 detected by standard tests The biological clock as an Discovery of a new genetic element important ally in the fight which has been used since 2007 ffects of nuclear receptors on E against inflammatory diseases for the molecular typing of inflammation and atherosclerosis Creation of the Longevity tuberculosis Discovery of the role of PPARs in Course, an innovative course controlling inflammation during in preventive medicine, in atherosclerosis. This discovery partnership with the university led to the creation of Genfit, a start-up initially hosted by Ins- hospital of Lille and the University of Lille 2019 titut Pasteur de Lille Cardiac and immune chronobio- 120 years since the opening of 1999 logy: important role of Rev-erba in cardiac chronobiology and Institut Pasteur de Lille Launch of the great creative First trials of the bilharzia vaccine: circadian immunity and collective challenge Bilhvax #TousUnPeuChercheurs
SPEEDING UP RESEARCH AND ACTING FOR BETTER HEALTH TOMORROW Over the past 60 years, men and women have But how are we ageing? And more specifically, gained on average a 14-year increase in life can we live better longer? At age 60 , on expectancy. Life expectancy in a good state average life expectancy is 20 years , ten of of health is increasing at a slower rate than life those in good health and the ten others with expectancy. When one knows that by 2060, a gradual loss of autonomy. So, extending the France will count 250,000 100-year olds, the period of life in good health is a challenge for question of ageing well becomes essential. research and public health. CANCER ALZHEIMER'S DISEASE 400,000 900,000 new cases detected in 2017. people in France are not diagnosed 1st cause of death CARDIOVASCULAR DISEASES DIABETES 140,000 3.3 million 9 deaths per year, of people with diabetes in France. 1,000,000 700,000 cases of heart failure individuals unknowingly live with diabetes INFECTIOUS DISEASES ANTIBIOTIC RESISTANCE 2.0 4 million 700,000 deaths worldwide deaths worldwide in 2019 (HIV, tuberculosis, malaria, viral hepatitis, etc.) 12,500 in France 480,000 case of multidrug-resistant 1st tuberculosis every year cause of death by 2050 Having historically led the way in the fight against infectious diseases, Institut Pasteur de Lille now hosts some of the most well-known international scientific experts in the field of antibiotic resistance 2.0.
STRATEGIC PROJECT OF THE INSTITUTE The Institut Pasteur de Lille was created in 1894 and behavioural determinants or "stressors" to respond to public health concerns at the end simultaneously affecting several organs, which of the 19th century, including the fight against have a generalised impact on the state of health infectious diseases, through the research work of the general public, the quality of life of our on pathogens, the development of vaccines fellow citizens and require complex and costly and serum and the promotion of preventive and treatments. hygienic measures. From the very beginning, Institut Pasteur de Lille has therefore organised In the last two decades, the life sciences have its actions around the following three objectives: also been deeply affected by the rapid growth high-level fundamental research, disease of the storage and computing capacities of prevention and the development of a healthcare computers, at the same time as the sequencing offer aimed at the general public, that complies capacities of the improvement of imaging with the core values of Institut Pasteur. technologies (molecular, cellular, in vivo) and the automation and miniaturisation of the The advances in research, vaccine development many search operations were producing data and the discovery of antibiotics and, more in exponentially growing volumes. As a result recently, antivirals, to which Institut Pasteur of these parallel developments, if they are de Lille has contributed, have resulted in a integrated within laboratories, our descriptions considerable reduction in the prevalence of of living things can be refined and more complex certain infectious diseases. mechanisms can be understood. During the 20th century, new diseases linked to changing lifestyles and to the increase in life expectancy have developed with an epidemic progression, such as the cardiovascular diseases, diabetes and metabolic diseases, cancers and neuro- degenerative diseases. At the same time, economic and industrial changes in societies have also given rise 10 to the emergence of other diseases linked to several rapid changes in the environ- ment (long-distance travel, intensification of livestock farming, pollution, climate change) such as antibiotic resistant infections, emerging infectious diseases and respiratory ailments. Even more serious are the frequent combinations of genetic, environmental, nutritional
Longevity objective POSITIONING AND STRUCTURING OF THE PROJECT To understand the significant changes in health needs, and fully exploit the rapid deve- lopment of scientific methods, Institut Pasteur de Lille has decided to organise its activities WHAT'S MORE, INSTITUT PASTEUR DE within an interdisciplinary and multi-sector LILLE HAS SET ITSELF TWO PRIORITIES: campus, whose central focus is to understand Degenerative diseases associated with the primary pathophysiological mechanisms of life styles, the extension of life time, and the most impactful diseases, in order to design changes in the environment: and develop diversified health products for - Diabetes and its complications sustainable healthcare: treatments, diagnostic - Cardiovascular and respiratory diseases assessments, vaccines and innovative disease - Neurodegenerative diseases prevention protocols. - Senescence, fibrosis and cancer Infectious diseases, in the context of antibiotic resistance These two objectives have strong scientific and methodological interconnections because both are linked to the functioning and ageing of innate and adaptive immunity, and of the microbiota. They can also be associated with effective disease prevention methods. THE STRATEGY OF INSTITUT PASTEUR DE LILLE CAN BE BROKEN DOWN INTO 4 INTERDEPENDENT OPERATIONAL OBJECTIVES 1 11 and industrial laboratories population according to the to facilitate the transfor- mechanistic hypotheses on mation of scientific results the other hand. Regarding into innovative healthcare this third point, the expe- Outlining an interdisci- products (drugs, diagnostic rience of Institut Pasteur plinary research platform assessments and vaccines, de Lille is unique in France, in pursuit of excellence disease prevention proto- and has no equivalent in with a holistic approach cols). the academic or hospital to the organisation, by infrastructures. 3 encouraging collabora- tions between academic 4 disciplines on the one hand and research units on the other, with the aim of identifying the earliest Conducting assessed stages of the pathophy- healthcare measures, with siological mechanisms of a progressive deployment Passing on "evidence- diseases, on which cura- from the Hauts-de-France to based" knowledge by tive or preventive action all of France. These actions participating in the "life- will theoretically be more will be implemented by buil- long" training offer, effective. Maintaining the ding intensified exchanges internally (career deve- highest level of scientific between research activities lopment) as well as in investigation thanks to on the mechanisms of partnership with the the most recent means of resilience and resistance to University of Lille and the observation and analysis stressors on the one hand I-site (ULNE) and the inter- will be sought. and disease prevention national network of Institut activities on the other. These Pasteur, and by communi- 2 exchanges naturally go both cating directly to the public ways: from the fundamental through conferences, and research (including human by exploiting all available and social sciences) to the channels and technologies, disease prevention actions to facilitate personalised Developing one's evaluated on the population communication for indivi- inter-sector ecosystem by on the one hand and from dual coaching in particular. bringing together academic the observation of the
There are eight founding research units of Institut implements a wide variety of complementary Pasteur de Lille. The 34 teams that make them heuristic approaches, used to create numerous links up gather together the initial scientific capital between epidemiological research (from the many (researchers, expertise, methods and results) in cohorts of "control subjects" and patients which line with the two topical priorities of the institute. they have formed), mechanistic and drug discovery These teams were highly rated during the 2019 (thanks to the many cell and animal models assessment wave of HCERES and the Specialised of diseases they have developed) and disease Scientific Commissions of Inserm. Within Institut prevention strategies (thanks to the unique disease Pasteur de Lille, they form the Interdisciplinary prevention infrastructure that hosts 15,000 men and Research Centre for Longevity (CTRL). women each year). This Interdisciplinary Research Centre for Longevity It works with the Centre for Health and Longevity which receives the public and designs, 01 RISK FACTORS AND MOLECULAR DETERMINANTS OF DISEASES LINKED TO AGEING implements and evaluates all the 02 INTEGRATIVE GENOMICS AND MODELLING OF METABOLIC DISEASES disease prevention activities, in collaboration with the hospitals 03 NUCLEAR RECEPTORS, CARDIOVASCULAR DISEASES AND DIABETES of the Hauts-de-France region. Diabetes-related preventive 04 TRANSLATIONAL RESEARCH ON DIABETES measures are conducted within the National Centre for Precision 05 "CENTRE D'INFECTION ET D'IMMUNITÉ DE LILLE" (LILLE INFECTION AND IMMUNITY Medicine, called "Précidiab", CENTRE) in collaboration with several hospitals in Hauts-de-France. 06 HETEROGENEITY, PLASTICITY AND RESISTANCE TO CANCER THERAPIES 07 IMPACT OF THE CHEMICAL ENVIRONMENT ON HUMAN HEALTH 08 MEDICINES AND MOLECULES FOR ACTING ON LIVING SYSTEMS EXCELLENCE IN RESEARCH AT THE HEART OF THE PROJECT 12 In 2015, the Institut Pasteur de Lille created the the most effective targets for therapeutic or Interdisciplinary Research Centre for Longevity preventive intervention. It is these early alterations where scientists are engaged in basic and applied (vulnerabilities which are not yet pathological) sciences to find the means to promote healthy that the Centre for Health and Longevity detects ageing by understanding, preventing and treating in "subjects" coming for consultation to offer the diseases linked to ageing. Because sustained them personalised disease prevention protocols homeostasis at every level (e.g. genome, in several areas (sensory, cognitive, metabolic, endoplasmic reticulum (ER), mitochondria, cell, skeletal, muscular). organ, organism) is the determining factor in Together, the teams at Institut Pasteur de the internal stability of organisms over time, Lille are studying the essential categories of our ability to cope with a variety of potential genetic, infectious, nutritional, environmental endogenous or exogenous stressors is the key to and behavioural stressors. They characterise the stability of our organism and to keeping it at the structure, functions and their impact on its highest functional level. Healthy ageing is possible by limiting exposure to preventable stressors and improving resistance and resilience to unavoidable stressors. One of the main objectives of our teams is therefore to identify the critical stress factors and their effects on the functions of cells, organs and organisms, as well as to understand the (patho)- physiological processes (sensors and effectors) triggered in response to stressors, especially during the prodromal phase when functional losses are too low to have a detectable effect on health. Theoretically, these early mechanisms are
Longevity objective the molecular and cellular biology of various of disease and, ultimately, the human and social target systems (neurological, immune, metabolic, sciences. Indeed, they have radically different neurological, respiratory, etc.) as well as the "business models". For example, genomics research integrated response of the organism as a whole requires a substantial initial investment to create through long-term in vivo studies. Regarding and maintain cohorts, but then produces results on the latter, we know that the role of hormonal, an ongoing basis. As for the "hypothesis driven", metabolomic, immune and inflammatory mechanistic and interventional studies needed responses is crucial. The importance of research to confirm the causal role of candidate genes or in metabolism and immunology on the Campus to further characterise biological or pathological is an important advantage. Regarding the study processes, they can be very slow and require a lot of cancerisation mechanisms, the institute will of work. The institute should increasingly turn to prioritise research into the processes that link strategies or technologies that are likely to bridge primary stressors, senescence, fibrosis and cancer. the "productivity" gap (such as high throughput technologies, non-mammalian intermediate The teams follow complementary heuristic models, organoids, etc.) Further downstream, the approaches, ranging from observational sciences institute's project has already aroused the interest (structural biology, Genome Wide Association of several researchers in the field of human and Study (GWAS), phenotyping, approaches asso- social sciences (HSS) and their integration within ciated with systems biology) to interventional life the context of the project has begun. Visions on sciences (such as in vitro and in vivo pharmacolo- research objectives that are shared with disease gy, microbiology, toxicology and chemical sciences prevention and the biomedical sciences is necessary (drug design, chemical biology, exploration of to ensure effective collaboration. chemical diversity, development of new chemical syntheses, immunomodulation and vaccines). By working on models of the disease, the latter esta- blish the causal role of the determinants identified by observational sciences. The continued development of excellence for the benefit of Institut Pasteur de Lille project depends on the connection between the observational sciences and interventional activities on models 13 In terms of academic disciplines, the strength science activities. It should be noted that in several of the Institut Pasteur de Lille campus resides in cases, translational projects on the discovery the close contacts that exist between biologists, of vaccines and drugs have also facilitated chemists, physicists and specialists in scientific new discoveries and the implementation of key data and public health. The creation and fundamental programmes leading to articles in maintenance of productive interfaces between the most highly reputed journals. The same type disciplines is essential to the creation of new of links will be established between the disease concepts, research tools and, ultimately, having an prevention research and HSS applications. impact in society. The main challenge is to define a scientific question that is common to scientists It is worth bearing in mind that the from different disciplines and to avoid the usual competitiveness of the researchers in the life customer/supplier relationship. Long-term sciences and healthcare is increasingly dependent relationships between chemists and biologists on cohorts and advanced observation tools such are particularly important in the field of drug as genomics, transcriptomics, proteomics as discovery. All means of interpersonal, formal or well as imaging, HCS/HTS, mass spectrometry, informal cultural exchanges must be practised on immunophenotyping, libraries of siRNA the campus. compounds, etc. on the one hand, and the processing of bio- and chemo-computer data on Translational research also feeds into basic the other hand. The campus teams have access research. Downstream from the study of biological to all of these tools, through several Equipex processes, the research includes translational platforms in particular. activities in the discovery and prevention plans of drugs and vaccines directly related to our basic
KEY FACTORS OF SUCCESS OF THE PROJECT As with any organisation that bases its work on innovative health products and unite its ecosystem. It research, the 4 key factors of lasting success are the is with the aim of enhancing these factors of success attractiveness (and influence), the creativity (risk that the foundation's project is directing the actions taking) and the willingness to translate discoveries into conducted on the existing capital. 0 1Attractiveness: increasing and renewing this presents an additional obstacle to the human potential. deepening of monodisciplinary research and a risk cademic excellence (increasing the influence A for careers and the team, which is often associated of the 3 Labex and 2 Equipex of the campus); with a higher probability of breakthrough disco- veries and is essential in translational research. International influence and exposure; ttractive (i.e. competitive) environment for A young researchers; 03 Willingness to translate discoveries into innovative and useful health products: marketing ttracting competitive funding (Horizon Europe, A them will be a driver of economic growth for the European Research Council (ERC), National institute, as has been the case twice in the past Institute & Health (NIH), Bill & Melinda Gates (CEREP, now Eurofins, and GENFIT). Foundation, etc.) Increasing scientific potential by adding to the 04 Uniting: In addition to these elements related institute's resources in HSS, including in the to the scientific integration of activities, Institut behavioural sciences and in health economics. Pasteur de Lille must also unite all the stakeholders associated with its activities: healthcare players 02 Creativity: the institute must cover (CNAM, ARS, Ministry of Health, private social the risk of the researcher, by promoting welfare players, hospitals, etc.), economic and interdisciplinary research in particular. Indeed, industrial players. 14 Institut Pasteur de Lille supports its research rent organs or diseases, which present identical, teams (management, help with the preparation of comparable or interdependent pathophysiological files, accommodation, scientific staff, investment mechanisms, e.g. fibrotic mechanisms. One of and maintenance in platforms) and stimulates the priority interdisciplinary bridges is research interdisciplinary research by funding cross-sec- on disease prevention, with the participation of tor activities between the teams from various researchers in the human sciences, biologists, disciplines (chemistry, biology, physics, medicine, doctors and paramedical staff. disease prevention) but also by studying diffe- KEY FIGURES 34 25,400 50,000 m 2 800 research teams 27 vaccinations campus employees nationalities per year 365 3 10 15,080 scientific LabEx technological Preventive papers (Excellence platforms Health Exami- Laboratory) including 2 equipex nations
Longevity objective THE DNA OF INSTITUT PASTEUR DE LILLE RESEARCH 661 1 500 8 5,000 researchers and technicians on campus articles (over 5 years) research units A/A+ citations/year epidemiology / genetics / pharmacology / working towards a common biochemistry / chemistry goal TIES WITH THE ECONOMIC WORLD PUBLIC HEALTH ACTIONS 44 6 2 15,000 active families start ups medicines consultations/year of patents under development 15 INTERNATIONAL SCIENTIFIC COLLABORATIONS Imperial College London Ghent University Helmholtz Center Munich University of London Harvard University Helmholtz association Italy University of Oxford Spain University of Cambridge Univ Oxford Estonia University College London National institutes of health NIH USA Karolinska Institutet University of California Erasmus University System Rotterdam Boston University Japan Boston Univ VA Boston healthcare system University of Helsinki Washington State University Switzerland
INTERNATIONAL RELATIONS Institut Pasteur de Lille is a leading research player diseases. The mission of Institut Pasteur de Lille is and is developing relationships with organisations to make progress with these two topics within the in different countries to share knowledge and network at the level of the Europe region. During speed up research. this meeting, Jérôme Weinbach, European adviser to the health managing director at the Ministry of Since November 2018, Institut Pasteur de Lille has Solidarity and Health, made a speech presenting been representing and coordinating the Europe the health priorities of the European Commission 16 region within the "Réseau International des within the framework of the future Horizon Europe Instituts Pasteur" (international network of Pasteur programme. institutes) under a 3-year mandate. From 12 to 15 November 2019, the directors of the 32 In 2019, in coordination with the "Institut Pasteur RIIP institutes met at the Pasteur Centre in Yaoundé Hellenique", the institute organised a meeting of in Cameroon to review the RIIP's activities and its the institutes of the RIIP Europe region in Athens outlook for the future. This meeting also involved from 4 to 5 September 2019. The 7 European discussions on the creation of new partnerships, institutes (Lille, Paris, Brussels, Saint Petersburg, regulations around the sharing of samples, as Sofia, Rome and Athens), represented by their well as several scientific priorities of the network directors, scientific directors and researchers, including antimicrobial resistance. Each RIIP region presented the strategies, technological platforms put forward a short and medium-term action and resources of each institute. Two major scientific plan on the topics that are specific to each region topics were selected for the Europe region: (antimicrobial resistance and neurodegenerative antimicrobial resistance and neurodegenerative diseases for Europe). COLLABORATING AT THE INTERNATIONAL LEVEL TO SPEED UP RESEARCH A bilateral meeting was organised on 28 resistance. Researchers from Institut Pasteur de November 2019 between 2 close neighbours of Lille met their Belgian counterparts to initiate the RIIP: Institut Pasteur de Lille and Sciensano, various scientific collaborations. its Belgian counterpart resulting from the merger of the ISP (Scientific Institute of Public Health) A key formative event of the longevity project of and the CERVA (Centre for Veterinary and Institut Pasteur de Lille was the 3rd International Agrochemical Study and Research). The objective Symposium on Longevity, which was held in of the meeting was to gain a better understanding December to address the subject of "Fundamental of the strengths of each institute, highlight the science at the service of good health throughout complementary strengths and initiate interactions life: disease prevention and treatment of age- between the researchers of both institutes in related diseases". More than 130 international the field of infectious diseases and antimicrobial scientists participated in this event.
Longevity objective Le Réseau International des Instituts Pasteur Une communauté humaine et scientifique mondiale unie par des valeurs et des missions communes au service de la santé. 32 INSTITUTS MEMBRES 23 000 17 PERSONNES 25 PAYS Laval Saint-Pétersbourg Lille Séoul Bruxelles Sofia Paris Shanghai Rome Téhéran Alger Athènes Hong-Kong Pointe-à-Pitre Casablanca Tunis Hanoï Vientiane Nha Trang Cayenne Hô-Chi-Minh-Ville Phnom Penh Dakar Niamey Conakry Bangui Nouméa Abidjan Yaoundé Rio de Janeiro Montevideo Antananarivo AMÉRIQUE Institut Pasteur de Lille AFRIQUE ASIE – PACIFIQUE Fiocruz (Rio de Janeiro) Institut Pasteur (Paris) Centre Pasteur du Cameroun (Yaoundé) Institut National d’Hygiène et d’Epidémiologie (Hanoï) INRS-Institut Armand-Frappier (Laval) Institut Pasteur de Saint-Pétersbourg Cermes Niger (Niamey) Institut Pasteur du Cambodge (Phnom Penh) Institut Pasteur de la Guadeloupe (Pointe-à-Pitre) Sciensano (Bruxelles) Institut Pasteur de Bangui Institut Pasteur de Corée (Séoul) Institut Pasteur de la Guyane (Cayenne) Institut Stephan Angeloff (Sofia) Institut Pasteur de Côte d’Ivoire (Abidjan) Institut Pasteur d’Hô Chi Minh Ville Institut Pasteur de Montevideo Institut Pasteur de Dakar Institut Pasteur du Laos (Vientiane) MAGHREB-IRAN Institut Pasteur de Guinée (Conakry) Institut Pasteur de Nha Trang EUROPE Institut Pasteur d’Algérie (Alger) Institut Pasteur de Madagascar (Antananarivo) Institut Pasteur de Nouvelle-Calédonie (Nouméa) Institut Pasteur d’Italie – Fondation Cenci Bolognetti Institut Pasteur d’Iran (Téhéran) Institut Pasteur de Shanghai, Académie chinoise des (Rome) Institut Pasteur du Maroc (Casablanca) Sciences Institut Pasteur hellénique (Athènes) Institut Pasteur de Tunis Pôle de recherche Université de Hong Kong – Pasteur Present in 25 countries across all the continents, numerous endemic disease zones, the RIIP has, the International Network of Instituts Pasteurs on multiple occasions, demonstrated its major (RIIP) groups 32 institutions united by common role as a sentry in the face missions and values for the benefit of the of infectious emergencies. DRIVEN BY THE ETHICS AND RESPECT general public. Notably installed at the heart of FOR INSTITUT PASTEUR'S CORE VALUES, THE INTERNATIONAL NETWORK OF INSTITUTS PASTEURS ENDEAVOURS TO IMPROVE HUMAN HEALTH.
RESULTS OF THE 3RD COLLABORATIVE AND EXPLORATORY CPER-CTRL CALL FOR PROJECTS 2018 In order to support interdisciplinary projects on de Lille (MEL) and the ERDF fund. The CPER-CTRL longevity, Institut Pasteur de Lille is coordinating the calls for projects aim to promote cooperation between CPER-CTRL programme for the 2016-2020 period teams in the region on new (State-Region plan contract - Interdisciplinary Centre issues related to longevity as Following the 3rd CPER-CTRL call for for Research on Longevity) funded by the state, the well as the emergence of new projects launched in December 2018, Hauts-de-France Region, the Métropole Européenne teams. 25 projects have been received and 11 projects were selected for funding after evaluation by independent experts and by the International Scientific Council (CSI). EXPLORATION PROJECTS (€50K) PROJECT NAME APPLICANTS PROJECT TITLE Anne TSICOPOULOS/CIIL Circadian clock of the lymphoid cells of the lungs CIRCASTHMA Hélène DUEZ/UMR1011 and severity of asthma Yves ROUILLE/CIIL Study of the interaction between peroxisomes and hepatitis C virus VIROPEX Yasmine SEBTI/UMR1011 replication complexes: impact on cell metabolism and oxidative stress COLLABORATIVE PROJECTS (€200K) PROJECT NAME APPLICANTS PROJECT TITLE Jérôme EECKHOUTE/UMR1011 Transcriptional control of the hepatic stellate cell activation associated LivFib Laurent DUBUQUOY/U1286 with hepatic fibrosis Ruben Hartkoorn 18 Alain Baulard/CIIL ProActiv-2 Activation of Pro-Antibiotic-2 Nicolas Willand/U1177 Elisabeth Pradel/U1286 Devrim KILINC/U1167 Medium-throughput screening based on co-cultures of neurons in SynapseScreen Sophie HALLIEZ/U1172 microfluidic chambers for physiologically relevant synaptic toxicity Jean-Sébastien ANNICOTTE/ Role of E2F1 in the loss of β cell function linked to inflammation during MELODY UMR8199 ageing Benoît POURCET/UMR1011 COLLABORATIVE PROJECTS (€90K) PROJECT NAME APPLICANTS PROJECT TITLE Muriel Pichavant/CIIL Smoking and obesity: multi-organ impact of metabolic reprogramming COMMONLY Florence Pinet/U1167 in longevity Consequences of the induction of endoplasmic reticulum stress in Isabelle WOLOWCZUK/CIIL DESTRESS-Flu white adipose tissue during infection with the influenza virus on the Steve LANCEL/U1167 severity of infection in the elderly Alicia MAYEUF-LOUCHART/ Circadian regulation of muscle regeneration during ageing: a ClockMuscleAging UMR1011 complementary approach in mice and drosophila Pierre DOURLEN/U1167 Rebecca DEPREZ-POULAIN/ Modulation of the UPR response by IDE: consequences on IDE-NASH U1177 inflammation, steatosis and ageing in NASH Nathalie HENNUYER/UMR1011 Réjane PAUMELLE/UMR1011 Role of FAT10 in hepatocyte senescence: impact in the development FATeNASH Albin POURTIER/UMR8161 of NASH Guillaume LASAILLY/U1286
Longevity objective LAUNCH OF THE 4TH CPER-CTRL (PHASE 4) CALL FOR PROJECTS In October 2019, Institut Pasteur de Lille launched of the 2 objectives of the Longevity research the 4th CPER-CTRL call for research projects. project. This call for projects is for the funding of Each project submitted must be presented by 2 collaborative projects and exploratory projects. teams from different units and be part of one 25/10/2019 10/12/2019 Q3 2020 Launch of the Hearing of projects Project call for projects by the CSI start-up 25/11/2019 March 2020 Project Examination of the reception funding request CPER-CTRL FINANCING 19 AN INTERNATIONAL SCIENTIFIC COUNCIL Bernard Folkert Thomas Edward THORENS, KUIPERS, THUM, PEARCE, Lausanne, CH Groeningen, NL Hannover, GE Freiburg, DE Cristina Miroslav Peter Alain LEGIDO-QUIGLEY, RADMAN, VANDENABEELE, FILLOUX, London, UK Split, Croatia Ghent, BE Londres, UK
SPEEDING UP RESEARCH FOR BETTER HEALTH TOMORROW
LONGEVITY: INTERDISCIPLINARY TEAMS FOR EXCELLENCE IN RESEARCH Institut Pasteur de Lille hosts a centre for Over the past ten years, these teams have research on longevity divided into eight units 1, endeavoured, together with their research with multidisciplinary, cross-sector skills. This partners, to get structured around excellence inter-disciplinary research programme which laboratories and facilities financed as part mobilises all Institut Pasteur de Lille teams of the "PIA" (investment programme for the aims to identify and characterise the genetic, future), including: environmental, metabolic, and infectious factors which contribute to lowering the functional LabEx dedicated to Alzheimer's disease a performance of cells and the organism, which is (DISTALZ) what we call ageing. This then makes it possible to prevent exposure to these factors, or to LabEx dedicated to studying diabetes a reduce their impact by stimulating the resilience (EGID) of cells and the organism with the assistance of innovative prevention strategies or treatment. research centre on infection and immunity a (CIIL) involved in the ParaFrap LabEx 01 Risk factors and molecular deter- minants of diseases linked to ageing n EquipEx dedicated to cellular imaging a 21 pharmacological screening (IMAGINEX 02 Integrative genomics and modelling of BIOMED) metabolic diseases n EquipEx dedicated to genomics a 03 uclear receptors, cardiovascular N (LIGAN‑PM) diseases and diabetes Institut Pasteur de Lille's campus boasts 04 Translational research on diabetes an exceptional concentration of high level facilities and technology platforms to serve 05 Centre d'Infection et d'Immunité de Lille all the researchers in the regional scientific (Lille infection and immunity centre) community. It also has the largest molecule library in Europe – the chemical library – where 06 H eterogeneity, Plasticity and Resistance thousands of tests are conducted every year, to Cancer Therapies2 helping in the discovery of new prescription drugs. 07 Impact of the chemical environment on human health 08 M edicines and molecules for acting on On 1 st January 2020 1 2 On 1 st January 2020, thereby replacing the Mechanisms of living systems Tumorigenesis and Target Therapies (M3T) unit
RISK FACTORS AND MOLECULAR DETERMINANTS OF AGING-RELATED DISEASES This unit focuses on the fight against age- determinants of Alzheimer's disease and cognitive related diseases, such as cardiovascular and disorders". Each of these teams gained international neurodegenerative diseases. Prof Philippe Amouyel recognition in the field of age-related diseases with coordinates the DISTALZ laboratory of excellence, a great openness to the general public in terms of dedicated to Alzheimer's disease. disease prevention for successfully extending the life expectancy of everyone in good health. Three teams interact on the "epidemiology and public health of age-related diseases", the PROF PHILIPPE AMOUYEL "molecular determinants of heart failure and MD PhD, University Hospital (CHU) of Lille ventricular remodelling", and on the "molecular UMR1167 - Labex DISTALZ University of Lille, Inserm, University Hospital of Lille, Faculty of Medicine, Institut Pasteur de Lille. DISSECTING THE RISK FACTORS TO EXTEND ventricular remodelling associated with heart THE LIFE EXPECTANCY OF EVERYONE IN failure to ultimately prevent this accelerated GOOD HEALTH ageing of the heart. This team, led by Dr Aline Meirhaeghe, analyses 22 the role of cardiovascular risk factors in the onset DECIPHERING THE GENOME TO BETTER and progression of cardiac and cerebrovascular UNDERSTAND ALZHEIMER'S DISEASE AND accidents and intellectual function disorders. Our FIGHT IT MORE EFFECTIVELY work is based largely on recording all cases of Alzheimer's disease is a disorder of the brain that cardiac and cerebrovascular accidents that occur develops over several decades. The team led by Dr in the region of Lille and its surroundings. Jean-Charles Lambert is interested in studying the susceptibility we all have for Alzheimer's disease. DETECTION OF CARDIAC AGEING IN ORDER In this way, we have identified the majority of TO ANTICIPATE IT MORE EFFECTIVELY genes involved in the onset of this disease. Our After a heart attack, the heart is often no longer research should result in the development of new able to eject enough blood to meet the body's avenues of treatment and prevention. need for oxygen, which causes heart failure. Dr Florence Pinet, who leads this team, is looking for the early markers of heart failure. She developed bedside clinical research protocols that she used to discover early biological markers of left
Speeding up research for better health tomorrow KEY EVENTS 1 Heart diseases and cerebrovascular diseases are inextricably linked. Using data from the Lille registers of ischemic heart diseases and strokes, we compared different indicators of these diseases in men and women aged from 35 to 74 between 2008 and 2014. We found that the heart attack rates exceeded the stroke rates, especially in men. The death rate was 2.2 times higher for heart attacks than for strokes, regardless of the age and sex of the patients. The same was true 3 of the fatality rate (percentage of people who To characterise individual susceptibility to die after a heart attack or stroke) which was 1.5 Alzheimer's disease, we need to compare times higher for heart attacks than for strokes the genomes of several thousand patients (Meirhaeghe et al Bull Epidemiol Hebd. 2019) and controls. This is the thinking behind our decision to increase the size of our samples by 25% (nearly 100,000 individuals in total) in 2019. This resulted in our discovery of five new genes supporting the involvement of APP metabolism and the Tau proteins that make up disease lesions in the brain (Kunkle et al, Nat Genet, 2019). We are also continuing to expand our working samples with the European project EADB 2 Heart failure remains one of the leading (European Alzheimer Disease Biobank), which causes of death worldwide. We identified we coordinate and which doubles the number the proteins in our blood that could predict of subjects studied and the ADES (Alzheimer premature death, within 3 years, among the Disease Exome Sequencing) project on the patients with heart failure hospitalised at the analysis of exomes of nearly 12,000 patients and Lille University Hospital. The patient's blood 10,000 controls. Thanks to this unique access to proteins were analysed using nanotechnologies the largest genomic study in the world, we will be (SOMAscan Slow Off-rate Modified Aptamer able to identify new avenues in the fight against technique). This was used to identify 203 proteins this disease more quickly. 23 that were modulated differently between the patients who died from cardiovascular death and those who were alive 3 years after the onset of their heart failure. We finally selected six proteins: C3 complement, cathepsin S, MAPK5, MMP1 and MMP7 to predict the risk of early death in these patients (Cuvelliez et al, 2019).
INTEGRATIVE (EPI)-GENOMICS AND MODELLING OF METABOLIC DISEASES UMR8199 included two teams: teachers, docs/post-docs, engineers, and 1 | "Genetic and Epigenetic of diabetes and obesity" technicians. The unit is at the origin of LabEx-EGID co-directed by Philippe Froguel and Amélie and of EquipEx-LIGAN-PM, the genomic platform Bonnefond, and 2 | "Molecular bases and modelling for personalised medicine. of metabolic diseases" directed by Jean-Sébastien PROF PHILIPPE FROGUEL Annicotte. It counts 63 individuals, researchers, PU-PH - Lille University, Lille University Hospital, LabEx, UMR8199, EGID, CNRS, Institut Pasteur de Lille, Lille University UMR8199 aims to understand the genetic and RHAPSODY (Risk assessment and progression pathophysiological mechanisms at the origin of of diabetes); as well as at the Research diabetes and obesity in order to make progress University Hospital (RHU). PreciNASH (PIA- towards personalised medicine for metabolic ANR, coordinated by François Patou, UMR1190). diseases. In these projects, our teams have a key role in producing and analysing (epi)genomic, The unit’s research objectives are to identify transcriptomic data, or derivative microbiomes, new genes implicated in diabetes and obesity, starting with large European cohorts of and to better diagnose forms of diabetes and diabetic and/or obese patients and control obesity of genetic origin which thus allows populations (including human samples selected personalised medicine according to genetic from pancreatic, hepatic, or muscular tissues). sub-type. All projects also have as an objective The environment’s epigenetic effects (which to better stratify genetic and environmental modify genetic activity) on the metabolism and risk factors, and the primary genetic causes, hepatic and renal complications of diabetes are of metabolic diseases at different ages in life. studied, consequently epigenetic variations in Different "multi-omic" approaches were taken pre-diabetic conditions such as gestational or by means of our genomic platform which is premature diabetes (EPx-GDM and EPIPRETERM unique in France (high-speed DNA and RNA projects). Thanks to the UMR8199's organisation, 24 sequencing, genotyping, and transcriptomic which is divided up between two teams, new analysis by DNA chips, digital molecular pathways can be identified leading to metabolic counting using NanoString technology). diseases, after which cellular or animal models Opening the LIGAN-PM platform to outside can be established in order to conduct in-depth teams makes it possible to initiate collaborative studies leading to the development of new research projects on other genetic diseases diagnostic and therapeutic strategies. Beyond such as intellectual deficiencies associated, or that, the goal of the European Genomic Institute not, with obesity, Crohn’s disease, breast and for Diabetes (EGID) is to offer optimal conditions ovarian cancers (using exome sequencing). for translational research on diabetes to truly The unit is a partner to several EU-H2020 ameliorate treatment of diabetics and their life. Innovative Medicines Initiative programmes : IMIDIA (Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes), DIRECT (Diabetes research on patient stratification) and
Speeding up research for better health tomorrow KEY EVENTS 1 Genetic factors play an important role in the development of obesity with a heritability of about 70%. About 5% of obese patients in France have a "rare" form of obesity known as monogenic. We discovered a new form of monogenic obesity which has the unique characteristic of leading to diabetes and 4 early hypertension, opening up diagnostic and In collaboration with AptamiR, a therapeutic perspectives. biotechnology company recently Loss-of-function mutations in MRAP2 are established in the Lille agglomeration in pathogenic in hyperphagic obesity with the Eurasanté incubator, the MetaboMIR industrial hyperglycaemia and hypertension. Nat Med. 2019 chair project entitled "Identification of new Nov; 25 (11): 1733-1738. Baron et al. therapeutic targets and their mode of action for the treatment of obesity, type 2 diabetes and non-alcoholic fatty liver disease", funded by the Métropole Européenne de Lille and I-SITE, aims 2 Common obesity is very polygenic, a to identify and validate new therapeutic targets feature which was established in 2007 by with good potential for technological transfer the Lille team: currently nearly 400 genes and their modes of action in order to ultimately contribute modestly to the risk of obesity. generate new treatments against certain We show that the most common obesity genes are metabolic diseases in humans, including diabetes, preferentially expressed in the brain. The surprise obesity and "NFALD/NASH" non-alcoholic fatty of this study is the lack of preferential expression liver disease. of common obesity genes in the part of the brain that controls hunger, i.e. the hypothalamus. On the other hand, we find an enrichment of these 5 genes in regions of the brain involved in the Our goal was to identify genomic sites reward and addictions mechanisms. where the genotype significantly affects The expression of genes in top obesity-associated the expression of genes located nearby loci is enriched in insula and substantia nigra within the genome. Our study identified novel brain regions involved in addiction and reward. genes for type 2 diabetes (T2DM) and eQTLs 25 Ndiaye et al. that have not yet been studied in the context of beta cell biology: their study will explain the pathophysiology of T2DM more effectively. Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated 3 Our UMR managed the Lille application that with type 2 diabetes. Mol Metab. 2019 Jun; 24: 98- brought together the University of Lille, 107 Khamis et al. Institut Pasteur de Lille, Inserm and the CNRS for the contest of the Future Investment Programme of University Hospital Institutes 2. An international panel of judges selected our PreciDIAB project which, thanks to funding from the state and local authorities (Métropole Européenne de Lille and Hauts-de-France region) obtained €23m for a period of 5 years with the objective of developing personalised medicine for diabetics within the framework of the new National Centre for Precision Medicine (PreciDIAB).
NUCLEAR RECEPTORS, METABOLIC AND CARDIOVASCULAR DISEASES UMR1011 studies the pathophysiological and epigenetic alterations. Therapeutic approaches mechanisms at the molecular and cellular level, centred on nuclear receptors are implemented. in preclinical models and in humans, at the origin of obesity, type-2 diabetes and its cardiovascular PR BART STAELS (atherosclerosis, heart failure, valvular diseases) PU-PH - Lille University, Lille University and hepatic complications (NASH). Hospital, U1011, Inserm, Lille University, Institut The impact on the immune system of circadian Pasteur de Lille, Lille University Hospital Metabolic pathologies such as obesity and complications further to myocardial surgery type-2 diabetes and their cardiovascular in humans. The receptor’s molecular action complications are the primary cause of death mechanism at the hepatic level was also not only in industrialised countries but also in specified. developing countries. Using fundamental and The contribution of other nuclear receptors and, translational approaches, UMR1011 studies the more generally, transcription factors to hepatic physio-pathological processes at the origin of functions was also highlighted (PPARα in septic these pathologies with a particular interest for shock, FXR, bile acid receptor, in the control of the nuclear receptors which represent choice neoglucogenesis and diabetes). Finally, we have therapeutic targets. interpreted a new cellular mechanism for the Over the course of 2019, major breakthroughs formation of brown adipose tissue. touched on the role of the Rev-erbα nuclear Unit 1011 published over the course of 2019. receptor, a major regulator of the circadian clock in controlling acute inflammatory 26 reactions in mice (hepatitis) and cardiovascular
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