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
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2019 ACTIVITY REPORT
Design and production:
Communications and sponsorship department - Institut Pasteur de Lille, Karbone14, Cam&Lou
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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
OBJECTIVE LONGEVITY
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, nutritionalLongevity 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 theThere 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 areLongevity 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 basicKEY 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 nationsLongevity 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 SwitzerlandINTERNATIONAL
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/U1286Longevity 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, UKSPEEDING 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) unitRISK 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 leftSpeeding 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) andSpeeding 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 cardiovascularYou can also read
