Ms Anne Negre-Salvayre

Ms Muriel Laffargue

Gerard Mr

Nash

Mr Ed Rainger

Jean-Louis Mr

Gueand

Paul Mr

Hofman

Raymond Mr

Bazin

Mr Jean

Louis Ferrier

The visit of the committee took place on December 9 th 2010. The work of the team and the project were presented by the team manager during one hour, which was followed by one hour of discussion and by the presentation of posters focused on the different aspects of the team activity. In the afternoon, the Committee met for further discussion on the project outlines.

• History and geographical localization of the research unit, and brief presentation of its field and scientific activities

The UMR INSERM 694 is part of the University of Angers, UFR of Medical Sciences, and is located in the CHU of Angers. The Unit project SOPAM « Oxidative Stress and Metabolic Diseases » implicates academic full time and teaching researchers and clinicians from the current INSERM Unit 694, and from the INSERM Unit U771. The scientific issues developped in the project deal with metabolic and inflamatory diseases and are focused on the metabolic function of mitochondria, the pharmacology of polyphenols, the role of microparticles in endothelial dysfunction and angiogenesis. The project includes the development of new therapeutic strategies in these diseases. As a consequence, the different aspects of the project associate basic fundamental research and clinical studies

• Management team :

Ramaroson ANDRIANTSITOHAINA, Director

• Staff members (on the basis of the application file submitted to the AERES) The group is very active and publishes extensively, mainly in mid-ranking journals, some articles being published in the best journals in their specialty (Blood, Diabetes, Am J Respir Crit Care Med, Faseb J, Chest, Am J Pathol., STKE). There is also an excellent technology transfer policy (5 patents, a start-up "in preparation", one INSERM contract of interface, one ANR, two PHRC). The originality of thematics, the crosscutting approaches associating clinical trials, appropriate animal models and basic research are important factors to ascertain the likelihood of the project's success, and should allow the group to succeed at a national and international recognition, and at an outstanding level of publications.

• Strenghts and opportunities

The committee wishes to emphasize:

-The originality of the scientific project -The strong interaction and complementarity between researchers and clinicians -The diversification of financial resources -The attractiveness of the group (arrival of two full-time EPST researchers in the team, presence of many PhD students)

-The efforts of valorisation and translation into clinical studies.

• Weaknesses and threats

The number of themes developed is important for the size of the team, with some potential risks of dispersion. An effort in the prioritization of themes could be done to make clearer the originality and the feasibility of each project (see below specific comments). The presence of experts in mitochondrial function/biogenesis is a great opportunity for working across disciplines, but the management of their integration needs to be clarified. It is not clear how section 3 (environmental toxins) integrates with work on MP and Polyphenols.

The team has a good publications record. Most 'primary' author papers are in mid ranking journals (33% with I.F between 2-4 and 40% with I.F 4-10).

• Recommendations

In view of the large number of themes, it is suggested to prioritize the projects and to focus on the most successful subjects, with regard to international competition. It would be worthwhile to publish fewer but more thoroughly constructed studies integrating in vitro, in vivo and patient studies since the team has now set the tools to do so. It is also suggested to submit to the very top outstanding journals. 3  Specific comments

• Appreciation on the results

Relevance and originality of the research, quality and impact of the results

The group has developed several original themes on oxidative stress and the mitochondrial function. An important part of the work and of the project is focused on the role of microparticles (MPs) in cardiovascular dysfunction occurring during the metabolic syndrome (MS) or in inflammatory diseases such as the "obstructive sleep apnea/hypopnea syndrome" (OSAHS) and intermittent hypoxia. The hypothesis is that Mps may behave as vectors of biological molecules and information between cells, with consequences on mitochondrial respiration, oxidative stress and endothelium function. The team recently reported a correlation between the circulating level of procoagulant Mps and endothelial dysfunction, vascular hyporeactivity and inflammation occurring during MS. Original and innovative therapeutic strategies are developped using engineered MPs carrying either Sonic Hedgehog to ameliorate endothelial function, or PPAR α to promote angiogenesis. The expertise of the team in this field is a strength of the application Another important research topic is the pharmacology of polyphenols and of their molecular targets, particularly the estrogen receptor ER α which could mediate, in part, the cardiovascular protective effect of these agents. The team leader is a recognized expert in this field.

Besides these projects, the team has a wide expertise in studying the mitochondrial metabolic function, in the presence of environmental toxicants and in pathophysiological conditions such as MS and in cell proliferative processes.

Quality and number of publications, scientific communications, thesis and other outputs

The scientific production of the team is very important (over 170 publications in the period 2006-2010, 60 % internal to the team), mainly in mid-ranking journals (33% with an I.F between 2-4 and 40 % between 4-10), with some articles being published in the best specialty journals (Blood, Diabetes, Am J Respir Crit Care Med, Cancer Res., J. Immunol., Faseb J, Chest, Am J Pathol, STKE). The team also produced 13 book chapters, 23 invited conferences, scientific communications with proceedings in international (18), and national (43) meetings, 6 communications without proceedings, 10 posters and 17 PhD thesis defended between 2006 and 2010.

Quality and stability of partnerships

The team has a strong ability to get regular funding regional (contracts Region and Canceropole Grand Ouest), national (participation in 3 ANR) or international (participation in two European contracts, DIOGENES, DEISA, contract France / FRSQ with Canada), funding from the charity sector (Fondation de France, National League against Cancer), or private sources (LVMH).

• Appreciation on the impact, the attractiveness of the research unit and the quality of its links with international, national and local partners

Number and reputation of the awards obtained by staff members, including invitations to international conferences and symposia

The visibility of the group and of the project leader is evidenced by the number of invited conferences at national and international meetings, as well as by the number of oral communications presented by the team members in international (28) or national (49) meetings over the last 4 years. The project leader also coorganized the Congress "New Frontiers in Cardiovascular Research" in Poland, 2008.

The team leader is board member of GRRC, and member of the scientific advisory board of Paris Est. The team members have international visibility in the field of metabolic diseases and mitochondrial regulation and in endocrinology (a team member is president of the French Endocrinology society).

Ability to recruit high levels scientists, post-docs and students, more particularly from abroad

The group has been reinforced by the arrival of two academic INSERM researchers (1 DR2 and 1 CR2). The attractiveness of the team for students is assessed by the presence of 3 post-doc and 7 PhD students, while 17 PhD thesis have been carried out during the period 2006-2010. International scientific exchanges exist with Canada (France/FRSQ Quebec), Italy and Spain.

Ability to raise funds, to successfully apply for competitive funding, and to participate to scientific and industrial clusters

The team has got a strong ability to obtain regular funding, from region (contracts Region Canceropole Grand Ouest), and national (participation in 3 ANR) or international contracts (participation in two European contracts, DIOGENES, DEISA, contract with FRSQ, Canada), as well as grants from Fundations (Fondation de France, National League against Cancer) or from private companies (LVMH).

Participation to international or national scientific networks, existence of stable collaborations with foreign partners

The team participates in two European contracts, DIOGENES, DEISA, and has a contract with FRSQ in Canada.

The concrete results of the research activity and socio-economic partnerships

The group is involved in the development of platforms (SNP Biogenouest, CIMATH). There is an excellent technology transfer policy, with 5 patents, a start-up currently under finalization, a contract of interface INSERM with the CHU (RA), 2 PHRC, 3 ANR.

• Appreciation on the management and life of the research unit

Relevance of the research unit organization, quality of the management and of the communication policy

The organization of the team is efficient in terms of translational research. Clinical researchers are present in the group and strong interactions exist between clinic and fundamental basic researchers. The techniques are controlled and the access to the various platforms is well-organized.

The organization set up seems appropriate, with the existence of a Managing Team Council including the director/project manager, researchers and teacher-researchers, as well as 2 members representing PhD students or post-doc. The council meets once a month.

Relevance of the initiatives aiming at the scientific animation and at the emergence of cutting edge projects

There is a scientific animation organized through meeting 'projects' and a weekly journal club.

Contribution of the research unit staff members to teaching and to the structuration of the research at the local level

Several teacher-researchers of the team are teaching in various disciplines within the Faculties of Medicine, Pharmacy, Sciences, PCEM1, PCEM2, Masters 1 and 2. The group is part of the Faculty of Medicine and the IFR 132 (the team leader is co-director of IFR132) at the University of Angers, and is also part of the CHU (several members of the team have clinical responsibilities).

• Appreciation on the scientific strategy and the project

The existence, relevance and feasability of a long term (4 years) scientific project

The project is the continuation of the previous work, and is subdivided into 4 independent sub-sections. It is planned to evaluate the role of MPs in the triad "Inflammation, cardio-vascular dysfunction and adipocytes" in metabolic syndrome (section 1), and in the obstructive sleep apnea/hypopnea syndrome" (OSAHS) (section 2). These sections include the hypothesis that plasma borne MPs can interact and modify the signalling and functional capacity of cells in the extravascular environment. The team is very skilled in the characterisation of MP origin, their content and their correlation with disease states.

The team expertise in this field is a strength for the application and its feasibility.

The section 3, focused on the consequences of environmental toxicants on mitochondrial function and metabolic diseases, needs justification, as it is not clear how this section integrates with work on MPs and Polyphenols.

In section 4, the applicants plan to develop new therapeutical strategies for metabolic diseases, including engineered MPs and polyphenols. This section is directly linked to the pathophysiological aspects of sections 1 and 2 since it represents a translational aspect. This section is original, well-balanced, and relevant particularly the part 4.3 on polyphenols which will use in vitro models (to determine the effects of polyphenols on adipogenesis and inflammation), mouse models of obesity and diabetes for studying the systemic effects of polyphenols and dietary trials in patients with OSAHS.

More generally, the feasibility looks good, each section appears well suited as a programme of research (except section 3 which needs further justification).

The project presents very original research topics, with high recovery potential. The numbers of themes being important with a risk of dispersion, it is necessary to better define the priorities and the connections between the different sub-projects.

Existence and relevance of a policy for the allocation of ressources

The team has shown a strong ability to obtain regular regional, national and international fundings, from Fundations and from the private sector. A majority of PhD students have research funding from the MESR.

Originality and existence of cutting edge projects

The development of engineered MPs carrying sonic Hedgehog or PPAR as new therapeutical tools for improving endothelial function and angiogenesis, is particularly original and should allow the group to access at an outstanding level of publications. Studies on the mechanism of action of reservatol and plant polyphenols and the role of the estrogen receptor are novel, and offer the possibility to develop new therapeutic agents. -la priorisation des pro3ets au re9ard de la compétition internationale : Mal9ré un effort de recentra9e réalisé sur la fusion de deuC é>uipes aAant deuC t?émati>ues différentes et complémentaires, nous sommes conscients de la difficulté >ui persiste et notamment les notions d#?omo9énéité t?émati>ue et l#imbrication entre la partie concernant les toCi>ues environnementauC et les travauC menés sur les microparticules et les polAp?énols7 Det effort >ui s#est poursuivi au sein de l#unité depuis le dép@t du dossier conver9e avec les recommandations du comité de visite7 Hinsi, nous allons prioriser nos t?émati>ues de rec?erc?es en développant principalement les points forts du pro3et concernant le r@le des microparticules dans la triade I inflammation, dAsfonction cardio-vasculaire et adipocAtes dans le sAndrome métaboli>ue, et au cours du sAndrome d#apnées du sommeil7 ,n intér:t particulier portera sur le r@le et la participation de la mitoc?ondrie dans ces pat?olo9ies en tenant compte l#eCpertise des membres de l#unité sur le su3et7 Il sera é9alement mis en avant les rec?erc?es sur les straté9ies t?érapeuti>ues pour lutter contres les effets délét=res de ces pat?olo9ies au travers du développement des microparticules en tant >ue vecteurs molécules protectrices et de nos connaissances sur les polAp?énols vé9étauC7 Hu travers de ces rec?erc?es, le but est de proposer des pistes de dia9nosti>ues et t?érapeuti>ues par une double approc?e mettant en 3eu les nutriments et les médicaments7 Doncernant l#impact de petites molécules contaminantes de l#environnement sur les fonctions mitoc?ondriales et les consé>uences induites sur les ré9ulations métaboli>ues cellulaires, le but est de vérifier l#?Apot?=se selon la>uelle les perturbations métaboli>ues peuvent eCpli>uer en partie les pat?olo9ies de stocKa9e7 Il s#a9it ici d#un pari scientifi>ue et le développement de cette t?émati>ue dépendra de l#évolution des résultats tr=s intéressants obtenus récemment et de la capacité de l#é>uipe E s#étoffer au cours du proc?ain contrat en potentiel ?umain7 "#ensemble de ces crit=res nous emm=ne E concentrer principalement nos efforts sur les points forts mentionnés par le comité de visite7 -Mal9ré un 9rand nombre de publication dans les meilleurs 3ournauC de spécialités et des 3ournauC de visibilité moAenne, il est recommandé d#au9menter le nombre de publications dans des 3ournauC E tr=s ?aut facteur d#impact et de 3ournauC 9énéralistes : 8ous avons maintenant mis en place les protocoles de rec?erc?e translationnelle et de rec?erc?e clini>ue avec des co?ortes bien établies et des approc?es fondamentales pluridisciplinaires >ui abordent l#ensemble des éc?elles du vivant du moléculaire E l#animal entier7 "a mise en commun de ces compétences au9mentera le potentiel de l#,nité E publier dans des I top outsandin9 3ournals L7 8ous allons concentrer notre effort pour arriver E ce but au cours du >uin>uennal E venir7

•

  Date and execution of the visit

  SummaryThe scientific project of this Unit is the logical continuation of the work developed by teams from INSERM U694 and UMR CNRS 6214-INSERM U771. The group comprises 4 full-time researchers EPST (2 DR2 INSERM, 1 DR2 CNRS and 1 CR2 INSERM), teacher-researchers and doctoral students. The project proposes a wide range of in vivo, ex vivo and in vitro studies to investigate the links between metabolic syndrome, microparticle formation/dissemination and inflammation. In vivo studies will include patients in two well controlled cohorts suffering from either metabolic syndrom or obstructive sleep apnea, as well as murine models of disease. In vitro studies will use diverse cell culture systems as well as advanced proteomic/genomic analysis systems to probe the research questions. Two aspects related one to the other, with strong valorisation potential are emphasized, on one hand the biological role of microparticles and polyphenols in metabolic and inflammatory diseases, and on the other hand their use as new therapeutical tools for improving the endothelium function and inflammation (newly engineered microparticles, polyphenols as dietary vasculoprotective agents).

•

  Production results cf. http://www.aeres-evaluation.fr/IMG/pdf/Criteres_Identification_Ensgts-Chercheurs.pdf A1: Number of permanent researchers with teaching duties (recorded in N1) who are active in research 7 A2: Number of permanent researchers without teaching duties (recorded in N2) who are active in research 2 A3: Ratio of members who are active in research among staff members [(A1 + A2)/(N1 + N2)] 0.9 A4: Number of HDR granted during the past 4 years 3 A5: Number of PhD granted during the past 4 years 17

Sciences du Vivant et Environnement

			Statistiques de notes globales par domaines scientifiques
					(État au 06/05/2011)
	Note globale	SVE1_LS1_LS2	SVE1_LS3	SVE1_LS4	SVE1_LS5	SVE1_LS6	SVE1_LS7	SVE2 _LS3 *	SVE2_LS8 *	SVE2_LS9 *	Total
	A+	7	3	1	4	7	6		2		30
	A	27	1	13	20	21	26	2	12	23	145
	B	6	1	6	2	8	23	3	3	6	58
	C	1					4				5
	Non noté	1									1
	Total	42	5	20	26	36	59	5	17	29	239
	A+	16,7%	60,0%	5,0%	15,4%	19,4%	10,2%		11,8%		12,6%
	A	64,3%	20,0%	65,0%	76,9%	58,3%	44,1%	40,0%	70,6%	79,3%	60,7%
	B	14,3%	20,0%	30,0%	7,7%	22,2%	39,0%	60,0%	17,6%	20,7%	24,3%
	C	2,4%					6,8%				2,1%
	Non noté	2,4%									0,4%
	Total	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%	100,0%
	*
	Intitulé UR / équipe	C1	C2	C3	C4	Note globale
	STRESS OXYDANT ET PATHOLOGIES MÉTABOLIQUES (SOPAM)	A	A	A	A	A
	C1 Qualité scientifique et production
	C2 Rayonnement et attractivité, intégration dans l'environnement
	C3 Gouvernance et vie du laboratoire
	C4 Stratégie et projet scientifique

les résultats SVE2 ne sont pas définitifs au 06/05/2011. Intitulés des domaines scientifiques Sciences du Vivant et Environnement • SVE1 Biologie, santé SVE1_LS1 Biologie moléculaire, Biologie structurale, Biochimie SVE1_LS2 Génétique, Génomique, Bioinformatique, Biologie des systèmes SVE1_LS3 Biologie cellulaire, Biologie du développement animal SVE1_LS4 Physiologie, Physiopathologie, Endocrinologie SVE1_LS5 Neurosciences SVE1_LS6 Immunologie, Infectiologie SVE1_LS7 Recherche clinique, Santé publique • SVE2 Ecologie, environnement SVE2_LS8 Evolution, Ecologie, Biologie de l'environnement SVE2_LS9 Sciences et technologies du vivant, Biotechnologie SVE2_LS3 Biologie cellulaire, Biologie du développement végétal

	INSERMUMRU.694
	Universitéd'Angers
	BâtimentIHURIS
	RuedesCapucins
	49100-ANGERSCedex
	RamarosonANDRIANTSITOHAINA
	DirecteurdeRechercheINSERM
	PorteurduProjet«SOPAM»
	SOPAM«StressOxydantetPathologiesMétaboliques»
	Observationsdeportéegénéralesurlerapportdévaluation
	"#ensemble des membres de l#,nité et le porteur du pro3et remercient le comité de visite pour leur travail et
	leur rapport7
	8ous avons noté avec 9rand intér:t et satisfaction les commentaires positifs rapportés dans cette évaluation,
	et tout particuli=rement l#ori9inalité du pro3et scientifi>ue, les relations étroites et complémentaires entre
	les c?erc?eurs et les cliniciens, la diversification des ressources financi=res, l#attractivité du 9roupe ainsi >ue
	les efforts de valorisations et le caract=re translationnel de la rec?erc?e >ui est mené7 8ous avons é9alement
	noté les évaluations positives sur la 9ouvernance7
	8ous avons apprécié les commentaires du comité sur les points forts de nos rec?erc?es concernant
	l#évaluation du r@le des microparticules en tant >ue mar>ueurs et vecteurs d#informations biolo9i>ues dans
	les pat?olo9ies comme le sAndrome métaboli>ue et le sAndrome d#apnée du sommeil et les straté9ies
	développées pour lutter contre celles-ci par l#in9énierie des microparticules elles-m:mes et par les
	polAp?énols vé9étauC7
	Doncernant les points E améliorer :


president Michel Cosnard

 Introduction History and geographical location of the unit

The unit has been created in 1994 and has been always under the direction of Mr Paul CALÈS. It is located in the University of Angers campus, in a recent building.

Management team

The laboratory is under the direction of Mr Paul CALÈS HCERES nomenclature SVE1_LS7 Épidémiologie, santé publique, recherche clinique, biomédicales

Scientific domains

Non-invasive markers of liver fibrosis, viral hepatitis, non-alcoholic fatty liver disease, portal hypertension, digestive oncology. The main focus of the unit has already been for some time research on the non-invasive assessment of fibrosis. Whereas this research was mainly focused on HCV-induced liver disease, it has recently shifted to the study of Non-Alcoholic Fatty Liver Disease (NAFLD). However, the unit also works on several topics within the field of hepatology and gastroenterology.

Unit workforce

Global assessment of the unit

The most extensive research output comes from the development and validation of non-invasive diagnostic tests for the assessment of liver fibrosis and more recently NAFLD. Some of these data have been published in highly ranked journals, are well recognized and are clinically useful. The unit is also involved in a large number of other topics for which their production and reputation are less strong. A strong point is the involvement in technology transfer with many patents (with licenses and royalties), a first start-up company already transferred in 2012 to Echosens and a second one planned to be launched.

The involvement in training is low with few PhD students and, more important, no post-doctoral fellows. The willingness to reduce the number of themes should be accompanied by a better-defined strategy in order to reach this aim and should make room for mechanistic studies.

Strengths and opportunities in the context

Strong involvement in patenting and technology transfer.

Very good recognition in the field of non-invasive diagnosis and prognosis of liver disease.

Loyal and committed staff.

Multidisciplinary staff.

Weaknesses and threats in the context

The unit is very dependent on its leader and the switch in the direction is a challenge that must be well prepared.

There are too many research programs.

The lab is missing PhD students and post-doctoral fellows. Some parts of the program (viral hepatitis) might not be sustainable in a competitive environment.

Recommendations

Decrease the number of themes in order to concentrate on promising topics.

Address not only clinical issues but also mechanisms.

Try to build a core of basic science by recruiting PhD students and experimented post-docs with a scientific background (not only medical doctors).

Unit workforce Number on 30/06/2015 Number on 01/01/2017 N1: Permanent

	professors and similar positions N2: Permanent researchers from Institutions and similar positions N3: Other permanent staff (technicians and administrative personnel) N4: Other professors (Emeritus Professor, on-contract Professor, etc.) N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.) N6: Other contractual staff (technicians and administrative personnel) N7: PhD students TOTAL N1 to N7 Qualified research supervisors (HDR) or similar positions Unit record PhD theses defended Postdoctoral scientists having spent at least 12 months in the unit Number of Research Supervisor Qualifications (HDR) obtained during the period 2	11 16 7 11 45 8 From 01/01/2010 to 13 16 30/06/2015 6 4

 Overall assessment of the unit Introduction

Evaluation report

This report is the sole result of evaluation by the expert committee, the composition of which is specified below.

The assessments contained herein are the expression of an independent and collegial reviewing by the committee.

Unit name:

Hemodynamics


 Introduction History and geographical location of the unit

The "unité d'épidémiologie animale" (UR 0346 INRA, "EPIA") belongs to the animal health division of INRA ("département de santé animale"). As of June 2015, the unit encompasses altogether 31 members including 22 permanent positions. The unit is located on two main sites, one at Theix, near and another one at Marcy l'Étoile in the VetAgro Sup veterinary campus near Lyon (6 members). In addition, one research engineer is located at the University Lyon 1 campus at La Doua. The unit ("laboratoire d'écopathologie") was created in 1978 to surpass the paradigm "one microbe -one disease" that did not explain many of the health problems in farming. In 1999, the unit was renamed "animal epidemiology" to promote the epidemiology discipline.

Management team

Scientific domains

The unit focuses on the analyses and modelling of infectious diseases, including the diversity and the effect of global change on emergence and transmission. Introduction This is a small but very dynamic unit working on the analyses and modelling of infectious diseases, including the diversity and the effect of global change on emergence and transmission. The unit members work at the interface between human, farm, and wild animal health (one health concept).

The unit has succeeded in meeting the previous recommendations, in terms of improving international visibility and publishing in better quality journals. They also formalized their collaboration with VetAgro Sup by formulating a proposal to become a joint research unit (INRA, VetAgro Sup).

Global assessment of the unit

The group is very strong in those research areas where they combine diversity with dynamics and evolution of pathogens. The scientific quality is excellent with many papers in good journals (given the size of the unit). The research of the unit has important societal implications, such as change in the perception of infection risk from alternative hosts, and transfer of knowledge to risk managers and policy makers.

Strengths and opportunities in the context

The strength of the unit is now in the analysis of pathogens with multiple hosts. This surpasses the traditional view that prevailed in animal epidemiology based on the one pathogen -one host concept.

From there, they have moved to pathogen interactions within hosts and they plan to include the nonpathogenic microbes i.e. the microbiota. This seems a natural extension to the existing research building on current strengths and using new technologies. Even though the study of the microbiota is now very timely, taking into account how microbiota diversity affects transmission represents a novel approach in animal epidemiology.

They have been involved in the study of zoonotic diseases (e.g. Lyme, Q-fever), which are topics in tight connection with societal demands (one health).

They are able to be multidisciplinarity in that they have all in their own hands: fieldwork, molecular biology, statistical and mathematical modelling. Given the small size of the unit, this represents a remarkable effort.

From the interviews, it seems that the management is successful despite the fact that unit members are located in two distant sites.

Weaknesses and threats in the context

There is definitely a need to attract more external funding, in particular European grants (H2020).

The unit seems to depend too much on the subjects on which funding is available even when these may not fit in the research strategy of the unit.

In the future the unit will have to adapt to a reduction of the technical help, as this is the policy within INRA and this will be a threat for the unit.

Even though the international visibility and profile has been improved, the unit still has a relatively modest international visibility, one issue being the accessibility for non-French speaking researchers.

Recommendations

The unit should focus on new original projects with societal relevance for which the expertise of the unit is useful. Strong examples of current approaches in this line are Lyme disease and Q fever. This involves extending these approaches to include humans as one of the hosts through cooperation with human medical doctors.

The unit should be more proactive to attract high profile young researchers as postdocs or junior INRA scientists.

There are opportunities, given the societal interest for the "one health" concept, to get more external funding.

The unit could increase its international profile by attracting postdocs and visiting scientists from abroad.

The unit should reconsider its strategy to have all the computing facilities (hardware and personnel) in house. A more effective alternative may be to share them with other units with similar requirements.

The methodology theme plays a very important role in providing tools that are used by the whole unit. This deserves to be better acknowledged.

 Detailed assessments Assessment of scientific quality and outputs

The unit has three missions: "detection of infectious diseases and associated risk factors", "dynamics (called circulation in some instances) and evolution of pathogens and their interaction with host", and "method development". In the past, there have been three research themes: "diversity", "global change", and "method development". The output is documented based on these latter themes. The strong points are the study of multi-host systems (including vectors as alternate host), and looking at the diversity of the pathogens in these hosts and the implications for population dynamics.

The unit has produced some important contributions on the circulation of tick-borne pathogens in mutli-host systems. In particular they found that the spirochete Borrelia burgdorferi, the agent of the Lyme disease, has a better transmission rate when infecting an introduced rodent species (the Siberian chipmunk) compared to native rodents. This result links the epidemiological risk of a human disease to the ecological concerns related to invasive species. A population genomic approach on B. burgdorferi also showed that distinct genetic clusters have different epidemiological and transmission dynamics.

The development of molecular biology techniques to identify several pathogens in the same sample is an important progress for this line of research. It allows moving from one pathogen and multiple hosts to more pathogens per host and to how these pathogen communities are transmitted between different hosts (species).

The original work of the group on communities of pathogens within a host can also be extended to work on beneficial or non-pathogenic microbes i.e. to the different microbiota of the host.

Overall the unit has published 117 papers in international peer-reviewed journals. These include high profile journals within the field of parasitology and infectious diseases, such as PLoS Pathogens (2), Trends in parasitology (1), emerging infectious diseases (1), eurosurveillance (2), Critical Reviews in Microbiology (1), ISME Journal (1), Frontiers in Microbiology (1). Seventy one percent of these papers have been published in journals that are classified as excellent (54%) or exceptional (17%) by the NORIA classification system. Members of the unit were first or senior authors in 60% of them, and 35% involved an international collaboration.

Short appreciation on this criterion

The study of differences among pathogens and how those are associated with different hosts/host species seem an important strength, also because of the combination of field data collection, molecular biological techniques and modelling. The scientific quality and outputs are excellent, given the size of the unit.

Assessment of the unit academic reputation and appeal

The unit participates in two European projects (EMIDA-VICE and EDENEXT) and the French LabEx ECOFECT, but they do not lead any of these. The unit has also been involved in three other national projects (ANR). Moreover, the members of the unit have organized three European workshops on the joint risk score in Paris.

A member of the unit has set up the R2A2 network on the use of antibiotics and the risk of resistance to antimicrobials in farm animals.

In other respects, the international profile of the unit is not very strong: PhD students and postdocs are essentially from France. Also, there are no visiting scientists from abroad e.g. for sabbatical leave.

A member of the unit is in the editorial board of Infection, ecology and epidemiology.

The quality and number of the other scientific contacts (invitation to 9 international conferences and 10 national ones) seem good for a group of this size. Given the quality of the research this implies that improvement is possible.

Short appreciation on this criterion

The academic reputation and appeal of the unit are very good.

Assessment of the unit interaction with the social, economic and cultural environment

The unit has partnership with public and private stakeholders. The collaboration with MERIAL is noteworthy: it results in the production of a weekly updated estimate of spatial explicit risks of tick abundance. This product has veterinarian practitioners as their main users. Members of the unit also participate to the development and use of the diagnostic tests on Q fever with the IDvet and Adiagen companies, and a collaboration with the fédération nationale des chasseurs to assess the seroprevalence of Q fever in wildlife (roe deer and wild boar).

One member of the unit is the chair of an interdisciplinary research network on the use of antibiotics in farm animals (R2A2).

The unit has produced 8 software applications for implementing different analyses (for instance the R package GraphScan).

Due to their expertise, researchers from the unit have been involved in more than one hundred expertise opinions for the European Food Safety Authority and ANSES.

The research results produced by the unit have been communicated through professional and technical meetings and publications and direct interaction with decision-makers (29 articles in professional journals and 11 invited talks in professional conferences).

Short appreciation on this criterion

The unit has excellent interactions with the social, economic and cultural environment.

Assessment of the unit organisation and life

A difficulty is the necessity to manage several distant sites: Theix with 21 members, Marcy l'Étoile with 6 members and Lyon 1 University (1 member). A scientific committee was created in 2014 with 4 persons: 2 directors, a chargé de recherche and an ingénieur de recherche. The committee was impressed by the organization of several meetings giving a dynamic life inside the unit in spite of this geographical spread: A general assembly meeting every month, a scientific meeting every month, a PhD day per year and a 2-day seminar. Moreover, three working groups "statmathinfo", "laboratory activity group", "genomic group" manage the unit's global strategy on topics covering various multidisciplinary themes. The unit's budget (without wages) has increased from 2011 to 2014 with a total today of about 400 kEuros. Moreover, the contribution from contracts to the budget has become larger than the contribution from INRA. Thus, the composition of the budget demonstrates the increased success of the unit in obtaining external funding. However, compared to other groups in INRA, this is still insufficient.

Each scientist is responsible for the budget of its own project. However, for large projects (over 60,000 euros), 10% are provided to the unit to fund projects having no -or insufficient -external support. This organised solidarity is praiseworthy as it allows, in particular, the promotion of innovative projects.

Finally, several transverse activities like "prevention", "quality", "skill-building", "computer management", "technical and scientific information", "laboratory analyses" and "fieldwork" are also organised collectively, showing again the positive atmosphere and attitude in the unit. Note that these transversal activities are managed by different persons of EPIA, leading to a wide sharing of responsibilities.

Short appreciation on this criterion

The unit has a very good to excellent management in spite of the difficulties coming from the geographical dispersion. It is remarkable that members have numerous exchanges and have all the opportunity to discuss with the management if necessary. Finally, the quality of atmosphere and wellbeing within the unit are noticeable. The regular and important improvement of budget shows a good management of the unit, but further improvement is needed to reach the level of other units in INRA. A challenge is to deal with less technical support and more researchers.

Assessment of the unit involvement in training through research

Unit members taught 60h per year at (1) the masters of University Joseph Fourier Grenoble in the field of modelling in biology and medicine, more precisely on dynamic modelling for pharmacokinetics and for epidemiology (22 h per year) (master 1 « ingénierie pour la santé et le médicament », master 2 « modèle, innovation technologique, imagerie », at (2) École des Hautes Études de Santé Publique (12h/year 2010-2012) (international master of public health) on zoonosis, and at (3) the doctoral school of university of Lyon ("évolution écosystèmes microbiologie modélisation" E2M2) (9h per year). The unit members also give lectures (about 9h per year) at "École Nationale des Services Vétérinaires", a post graduated school.

Twelve PhD theses were defended, 8 PhD theses are still in progress and 10 Master 2 are supervised. In 6 veterinary in equine medicine interns are supervised for their research report. The unit belongs to the "école doctorale des sciences de la vie, santé, agronomie, environnement" (ED 65).

Short appreciation on this criterion

The unit is involved in various national and international courses. The number of hours per year is reasonable but the unit could profit from doing more teaching at the international level. The number of PhD theses (defended or in progress) has considerably increased since the last period, which reveals an increasing commitment to the PhD training. Overall, the unit has a very good involvement in training.

Assessment of the strategy and the five-year plan

The general objective of the research unit is to study the epidemiology of infectious diseases in relation to ecological and evolutionary processes. The research program is structured in three main research themes: detection of infectious diseases and identification of risk factors, ecological and evolutionary processes that shape the transmission processes and development of new methods. The three main research themes fit into the research priorities defined by INRA and VetAgro Sup. The research strategy is a continuation of the strategy followed until now by the unit.

The choice of research topics is timely, as there is a demand from society and policy makers for improved knowledge on the surveillance and management of animal infectious diseases, especially those with a zoonotic component.

The different themes include research on a wide range of pathogens, which is not a problem as the nature of disease outbreaks often modifies the research agenda of this type of institutes, and the comparison of a range of pathogens with different characteristics may be an added value. However, how the interactions and synergies between themes will occur is not always clear. A good integration of the three research themes through better exchanges would confer an added value to such a small unit The SWOT analysis may benefit from a better identification of potential new stakeholders for the research of the unit especially at the international level. Cooperation with human medicine is important for the study of zoonotic diseases.

Given the current expertise of the unit members, the planned work seems certainly feasible.

Short appreciation on this criterion

The strategy for the next five years is excellent.

N7

  Other professors (Emeritus Professor, on-contract Professor, etc.) N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.) 1 N6: Other contractual staff (technicians and administrative personnel) 1

Postdoctoral scientists having spent at least 12 months in the unit 2

Number of Research Supervisor Qualifications (HDR) obtained during the period 2  Overall assessment of the unit

The visit started at 8:30 a.m. with a short presentation of the HCERES missions by the scientific delegate. The head of the unit presented then the past research activity and achievements. The deputy head presented the future plan for the up-coming five years, followed by the presentation of the three scientific themes of the unit (global change, biodiversity, methods). The panel then had meetings with the faculty and technical staff. After lunch, the panel met the PhD students and post-docs, the representatives of INRA and VetAgro Sup, the representative of the doctoral school, and finally the head and the deputy head of the unit. The closed door meeting of the panel started at 3:30 p.m. and finished at 6:00p.m. We have received the evaluation report of the HCERES committee. We are thankful for the constructive analysis and recommendations. We thank you again for the quality of the discussions we had during the visit of the committee on January 13 th . Sincerely, Gwenaël Vourc'h Karine Chalvet--Monfray Directrice Directrice adjointe