Evaluation report

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

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

Unit name:

The Laboratory of Molecular Biology of the cell The Gerland site includes the École Normale Supérieure de Lyon (ENS), University Claude Bernard Lyon 1 (UCBL) and public research laboratories. These are multi trustee laboratories including the LBMC, IGFL (Institute of Functional Genomics), IBCP (Institute of Biology and Protein Chemistry), RDP (Laboratory of Plant Reproduction and Development), CIRI (International Center for Infectiology Research) for Biology. The Gerland site also comprises labs or departments in Maths, Physics, Chemistry, the complex systems institute as well as the humanities/social studies campus (Descartes).

The LBMC was founded in 1987 at the opening of the ENS de Lyon with the aim to cover most of life science disciplines in order to have within this institution the competences necessary for its two core missions: research and teaching. Since its creation, the LBMC has been administered as a "Unité Mixte de Recherche"(UMR), supported by the ENS de Lyon and the CNRS. The UCBL and the Lyon Hospices (HCL) also supported the laboratory, in particular through the presence of two joint-appointments within the LBMC and several transversal projects.

Management team

Mr Laurent SCHAEFFER heads LBMC since 2008 and Mr Pierre JALINOT acts as deputy director in charge of the preparation of the future contract since 2014. In 2016-2020, Mr Pierre JALINOT will lead LBMC supported by the deputy director Mr Didier AUBOEUF.

HCERES nomenclature

Principal: SVE1_LS3 Secondary: SVE2_LS8, SVE1_LS1 2  Overall assessment of the unit

Global assessment of the unit

The LBMC investigates basic questions of molecular cell biology. The thirteen research teams of the LBMC work along three main research axes: i) genome dynamics, maintenance and expression (team 2, 3, 4, 6, 8, 9, 10, 12) ii) cellular and molecular pathological processes (team 1, 4, 5, 7, 9, 12 interested by Stress, cell death & cellular reprogramming) and iii) developmental cellular processes (team 3, 7, 10, 11, 13 interested by multiscale integration of biological processes & single cell stochasticity). A common theme is the establishment and use of quantitative systems biology approaches to understanding the physiopathology processes such as Cancer, aging & neurodegenerative diseases. Team leaders have already obtained highly competitive grants (ANR -Chaire d'Excellence, ATIP, ERC). Team leaders at LBMC have national and international recognition (national and international highly competitive grants, memberships, invited conferences, chair of meetings or member of organization committee, CNRS Bronze medal). The LBMC can also benefit from the state-of-the art facilities and the broad panel of technologies and platforms provided by the Federation of the Technical platform on the side of Lyon Gerland (SFR UMS3444 BioSciences Gerland-Lyon Sud). While the LBMC benefits from access to genomics and proteomics facilities, they have established a state-of-the-art BioImaging Core Facility, which was funded by ANRequipex and offers cutting edge technologies for live and super-resolution microscopy together with the necessary expertise for technical support and maintenance.

The LBMC continues their successful emphasis on experimental approaches in molecular, cellular and developmental biology and now complements this work with quantitative systems biology methods. This combined strategy is reflected in the shared leadership by Mr Pierre JALINOT and Mr Didier AUBOEUF.

Strengths and opportunities in relation to the context

The new scientific focus and direction of the LBMC is promising as well as timely and is supported by the recent recruitment of several promising young scientists. The new scientific direction places the LBMC at the cutting edge of modern cell biology with the opportunity for significant scientific contributions with high impact in the scientific community. This should improve the international visibility and attractivity for fruitful collaborations and help the recruitment of excellent students and scientists. This new direction should also open new opportunities for new grants, translational research and collaborations with national and international companies. A "bio-informatic" open space will be created, in which 20 bio-informaticians (permanent and non-permanent staffs from several teams) will be working together. The LBMC has the ambition to be a leading research unit with strong development in computational methods applied to biological questions.

Weaknesses and threats related to the context

The major challenge is the international competition with better funded groups. The modern cell biology planned by the LBMC for the next five years is ambitious and expensive. The LBMC has several excellent and promising groups that are, however, rather small and have limited resources. The success will depend on the ability of the LBMC teams to secure additional funding, establish fruitful collaborations and synergise with other institutes in Lyon.

Another challenge is the establishment of a new open space for computational and system biology projects which will not be associated with a bioinformatics research lab.

Almost half the number of the current staff will be renewed in the next contract.

Recommendations

The experts committee recommends that the bioinformatics open space be further strengthened by the recruitment of expert scientists that do not only use computational methods but also actively develop new algorithms. Teams contributing to the bioinformatics open-space must participate in its scientific emulation through regular scientific meetings involving bio-informaticians team leaders and other team members.

Also, care should be taken to avoid that young team leaders spread out too thin in countless collaborations potentially delaying or preventing the establishment of their own research profile/reputation. Given the limited resources available, the number of experimental systems and research topics should be limited accordingly to foster synergies and to allow effective and sustained support of promising and successful research teams.

Continue development and structuration of the system biology axis including multidisciplinary approaches around interfaces with Mathematics, Physics and Chemistry from close by institutes.

Several research groups have found their niche but need to be reinforced to reach a more mature level and increase their international visibility. The LBMC needs to improve their international visibility by co-organizing and attending international scientific meetings and by joining forces to obtain more publications in high impact journals.

Mentoring group leaders who are less sucessful in getting competitive grants and provide sufficient support to the young groups (redeployment of permanent staff should be considered).

Continue developing platforms within the SFR Biosciences Gerland frame, specifically reinforcing the genomic/transcriptomic facility.

  , Technische Universität Darmstadt, Germany Ms Claire FRANCASTEL, CNRS, University Paris 7 (representative of the CSS INSERM) Mr Vincent GALY, Institut de biologie Paris-Seine, Paris Ms Ines HELLMANN, Ludwig-Maximilians University Munich, Germany Mr Bernard MIGNOTTE, Laboratoire de Génétique et Biologie Cellulaire Université de Versailles (representative of the CNU) Mr Cosmin SAVEANU, Institut Pasteur, Paris Mr Pascal THEROND, Institut de Biologie Valrose, Centre de Biochimie, Université de Nice Sophia Antipolis (representative of the CoNRS) Ms Julie THOMPSON, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie, Faculté de Médecine Strasbourg Mr Albrecht vON BRUNN, Max von Pettenkofer Institute, Germany Scientific delegate representing the HCERES: Ms Maryam MEHRPOUR Representatives of the unit's supervising institutions and bodies: Ms Bénédicte DURAND (representative of the Doctoral School n° 340) Ms Germain GILLET, University of Lyon 1 Mr Laurent KODJABACHIAN, CNRS Mr Jean François PINTON, ENS Ms Pascaline TOUTOIS, CNRS, Rhône Auvergne 1  Introduction History and geographical location of the unit The Laboratory of Molecular Biology of the cell (LBMC) is part of the Charles Mérieux Gerland site of the new University campus of Lyon located on a main road linking the Pasteur bridge to the south of the Lyon metropolitan area.

Unit workforce Unit workforce Number as at 30/06/2014 Number as at 01/01/2016 N1: Permanent

	professors and similar positions	29	5
	N2: Permanent researchers from Institutions and similar positions	30	22
	N3: Other permanent staff (without research duties)	30	22
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	N5: Other researchers (Emeritus Research Director, Postdoctoral students, visitors, etc.)	41	22
	N6: Other contractual staff (without research duties)	8	2
	TOTAL N1 to N6	138	73

Unit workforce Number as at 30/06/2014 Number as at 01/01/2016

	Doctoral students	28
	Theses defended	47
	Postdoctoral students having spent at least 12 months in the unit	47
	Number of Research Supervisor Qualifications (HDR) taken	11
	Qualified research supervisors (with an HDR) or similar positions	29	23


Evaluation report

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

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

Unit name:

Institut de génomique fonctionnelle de Lyon The Gerland site includes ENS de Lyon, Université Lyon 1 and public research laboratories. These are multi trustee laboratories including the IGFL, IBCP (Institute of Biology and Protein Chemistry), LBMC (Laboratory of Molecular and Cellular Biology), RDP (Laboratory of Plant Reproduction and Development), CIRI (International Center for Infectiology Research) for Biology. The Gerland site also comprises labs or departments in Maths, Physics, Chemistry, the complex systems institute as well as the humanities / social studies campus (Descartes).

The IGFL is a young institute and moved to a new modern research building in August 2012. The IGFL is a 3200m 2 building including 1500 host labs core facilities, offices and services. This new building is well equipped, displaying the most recent genomic technologies.

Management team

Mr Vincent LAUDET, supported by the deputy director Ms Françoise BLEICHER, heads IGFL since 2008. In 2016-2020, Ms Florence RUGGIERO will lead the IGFL, supported by the deputy director Mr Frédéric FLAMANT. To ensure a smooth transition between the present and future direction, she has been nominated in September 2014 deputy director of IGFL.

HCERES nomenclature

Principal: SVE1_LS3 Secondaire: SVE2_LS8, SVE1_LS1

Global assessment of the unit

The IGFL is an outstanding research institution in the European landscape with unique profile. The striking feature of the IGFL is the thematic coherence which enables both strong collaboration and intellectual exchanges on fundamental questions in evolution, development and integrative physiology. The IGFL's research in functional genomics aims to elucidate how the whole genome controls the development, function and evolution of animal species. The teams that currently constitute the IGFL are interested by 3 research axes: I) genomics of adaptation and evolution (teams 5, 6, 12,13); II) development and regeneration (teams 1, 5, 8, 9); III) Integrative physiology and physiopathology (teams 3, 6, 7, 8, 9, 11).

It was composed of 12 teams when created in 2006. The strong leadership, capacity of the managing directors together with the help of a carefully selected and high profile SAB in recruiting outstanding scientists to the IGFL for the next 5 years includes the emergence of 4 new teams (12 teams in total for the next 5 years (numbered 1-13 with skip). Among these 12 teams, 1 is led by a women.

Most of new external team Leaders (national and international) whose have recently established their group at the IGFL have already obtained highly competitive grants (ANR-Chaire d'Excellence, ATIP-ERC). This IGFL recruitment policy has enhanced diversity of the research topics, technology and model organisms. Several teams develop research programs on mineralized tissues, molecular endocrinology, embryonic development and the genomics of adaptation, physiopathology and oncogenesis. The successes of these new-recruited team leaders have also contributed to increasing their international visibility and have led to hiring a significant number of non-French post-docs. Most of the team leaders at IGFL have national and international recognition (national and international highly competitive grants, memberships, numerous invited conferences, chair of meetings or member of organization committee, CNRS Bronze medal).

The IGFL has substantially developed large-scale and global transcriptomic and genomic approaches through the development of an in-house Next Generation Sequencing (NGS) platform. IGFL also facilitated the diversification of species (non-model organism) used in the institute, by the establishment and expansion of in-house animal facilities including that for aquatic and semi-aquatic animals, drosophila, zebrafish and rodents. The IGFL can also benefit from the state-of-the art facilities and the broad panel of technologies and platforms provided by the Federation of the Technical platform on the side of Lyon Gerland (SFR BioScience-Gerland).

The IGFL receives strong support from the university and the ENS of Lyon that has allowed developing a strong and convincing program for training young biologists. Among the IGFL research staff 15 professors and assistant professors are from the ENS of Lyon and the Université Claude Bernard Lyon 1. This strong link between research and teaching promotes national visibility and helps to attract talented students to the IGFL. The Institute is nicely organized. The spirit in the "IGFL" is characterized by enthusiasm and a strong community feeling to which all members from all academic levels, including PhD students, postdocs, scientists, technicians and the team leaders, equally contribute. All the needed committees have been set up, and they appear to be nicely organized and very efficient.

Strengths and opportunities

The IGFL has a panel of excellent to outstanding teams with complimentary expertise and is housed in a brand new modern research building offering state-of-the art facilities.

There is impressive dynamics in recruiting excellent junior scientist at a regular basis in combination with diversity of experimental systems at the IGFL.

The international nature of the PhD student, post doc and team leader recruitments.

The reputation of team leaders and a strong track record of publications in journals with high to very high impact factors.

High diversity of the conventional and unconventional model.

Weaknesses and threats related to the context

A challenge for the future will be to keep up with the spirit and vision of the founder generation of the IGFL in times of constantly decreasing funding for basic research. It also will be important to stabilize the limited size of the unit (12 teams). Moreover, the limited number of permanent positions (lab manager, researcher) can fragilize young teams. The presence of a state-of-the art equipped seminar room or lecture theatre would certainly support scientific communication within the new building.

Recommendations

The IGFL currently benefits from a unique and internationally recognized identity. The recommendation, therefore, is to maintain by all means the unique features offered by the IGFL in the context of the planned association with the with UMR 5242 (plant reproduction & development, PRD directed by Mr Teva VERNOUX) and UMR 5239 (Laboratory of Molecular Biology of the cell, LBMC directed by Mr Pierre JALINOT), within a new ICB (Integrative Cell Biology) center.

  -CUIF, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette (representative of the CoNRS) Mr Jean François BRUNET, IBENS, Paris M Thierry DARRIBERE, Université Pierre et Marie Curie (representative of CNU) Mr Tomislav DOMAZET-LOŠO, Ruđer Bošković Institute, Zagreb, Croatia Mr Michel GOLDBERG, Université Paris Descartes Mr Krzysztof JAGLA, Université de Clermont-Ferrand Mr Jean-Stéphane JOLY, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette (representative of INRA) Mr Stefan SCHULTE-MERKER, Hubrecht Institute, The Netherlands Scientific delegate representing the HCERES: Ms Maryam MEHRPOUR Representatives of the unit's supervising institutions and bodies: Ms Germain GILLET, Université Lyon 1 Mr Laurent KODJABACHIAN, CNRS Ms Françoise MONEGER (representative of ED n°340 « Biologie Moléculaire Intégrative et Cellulaire ») Mr Jean-François PINTON, ENS Lyon Ms Pascaline TOUTOIS, CNRS 1  Introduction History and geographical location of the unit The Institute of Functional Genomics (IGFL) is part of the Charles Mérieux Gerland site of the new university campus of Lyon located on a main road linking the Pasteur bridge to the south of the Lyon metropolitan area.

  Unit workforce

	Unit workforce	Number as at 30/06/2014	Number as at 01/01/2016
	N1: Permanent professors and similar positions	15	13
	N2: Permanent researchers from Institutions and similar positions	18	14
	N3: Other permanent staff (without research duties)	21	22
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	N5: Other researchers (Emeritus Research Director, Postdoctoral students, visitors, etc.) Includes contract personnel with research duties (not post docs)	15	14
	N6: Other contractual staff (without research duties)	12	8
	TOTAL N1 to N6	81	71
	Unit workforce	Number as at 30/06/2014	Number as at 01/01/2016
	Doctoral students	16
	Theses defended	37
	Postdoctoral students having spent at least 12 months in the unit	7
	Number of Research Supervisor Qualifications (HDR) taken	5
	Qualified research supervisors (with an HDR) or similar positions	21-
	2

 Overall assessment of the unit


Evaluation report

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

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

Unit name:

Management team

The governance of the Institute is organized as follows: the director, assisted by the deputy director, designed by vote of the general assembly (all members of the staff) implements the strategy defined both from a scientific and organizational point of view. The steering committee (director, deputy director and team leaders) proposes the general scientific strategy and discusses it with the laboratory council. This laboratory council is chaired by the director, and composed of the steering committee, plus elected members representing each staff categories within the institute. The laboratory council also includes Health and Safety representatives and core facility representatives. The laboratory council defines organizational strategy and discusses the scientific strategy proposed by the steering committee. Experts within relevant fields of research could be invited (no right to vote). A Scientific Advisory Board will be constituted at the creation of the Institute and will provide advices both on scientific and organisational outputs. The governance and rules are detailed in a "IRSD Rules of Procedure" document. 2  Overall assessment of the unit

HCERES nomenclature

Global assessment of the unit

This is a very relevant proposal of restructuration to favor interactions of researchers with complementary backgrounds, who share a common vision of promoting digestive health. All research activities focus on a better comprehension of key pathological events related to digestive diseases. The diversity of competences of the IRSD allows to addressing key questions in the fields of both human and veterinary medicine in the context of digestive health.

Strengths and opportunities in relation to the context

-This is a unique research structure on digestive health, that has the strong support of all governing/funding bodies (Inserm, ENVT, Inra, University Toulouse 3); -all the members of the future institute have been involved in the decisions related to the project of creation of the unit;

the new constellation will provide multidisciplinary and complementary research disciplines within the field of the digestive tract physiology and pathology, and will reinforce the translational research in the field of digestive health;

the objective to attract and recruit several people with key novel expertises has been reached; -all members of the unit have a good policy in obtaining funding from different sources (national, international, industrial); -very strong scientific recognition at the international level, with adequate scientific proposals for the future, encouraging the independency of young and promising researchers;

strong leadership of the director and management skills that promote the motivation and create a positive atmosphere.

Weaknesses and threats related to the context -Two options have been proposed concerning the expected location in 2020, that should be clarified as soon as possible to keep the visibility;

the facilities (personal, material, facilities) that could be kept from the previous research center might be clarified.

Recommendations

-There is a need to reinforce the means to promote the translational research in each group; -if space is available, it would be nice to attract new groups with complementary expertise;

future recruitment might take into account the generation turnover.

  , Inserm, Clermont-Ferrand Mr Pascal DE SANTA BARBARA, Inserm, Montpellier (representative of the CSS Inserm) Ms Teresa FRISAN, Karolinska Institut, Stockholm, Sweden Mr Hervé PUY, Centre de recherche sur l'inflammation, Inserm, Paris Scientific delegate representing the HCERES: Mr Jean GIRARD Representatives of the unit's supervising institutions and bodies: Ms Emmanuelle MAGUIN, INRA, MICA department, Paris Mr Alain MILON, ENVT -École Nationale Vétérinaire de Toulouse Ms Anne ROCHAT, Inserm, Paris Mr Philippe VALET (representative of the Doctoral School ED n°151 "Biologie Santé Biotechnologie") Mr Alexis VALENTIN, Paul Sabatier University, Toulouse

  location of the unit The proposal consists in a restructuration of the CPTP (Centre de Pathophysiologie de Toulouse Purpan -Inserm laboratories located at the Hospital site of Toulouse Purpan), a center created in 2002 and renewed in 2007 and 2011. This center mostly focuses its research activities on immunology and to a lesser extent on infectious diseases. The proposal is to create a new entity (2016-2020): the digestive health research institute (IRSD: Institut de Recherche en Santé Digestive), that will be located for the next term in the same place (Toulouse Purpan). The unit was previously organized in 3 research teams: team "Mediators of Inflammation and Pain", headed by Ms Nathalie VERGNOLLE; team "Molecular and Cellular Pathogenesis of E. coli infections" headed by Mr Eric OSWALD and team "Genetics and Iron Metabolism" headed by Ms Marie-Paule ROTH and Ms Hélène COPPIN. Those three founding teams have a common vision of the scientific strategy that leads to the demand of creation of the IRSD institute. They will focus their research program (and have renamed their teams) in order to offer a strong research task force in their respective field: intestinal pathophysiology (Ms Nathalie VERGNOLLE's team), host-microbe interaction (Mr Eric OSWALD's team) and iron metabolism (Ms Marie-Paule ROTH/Ms Hélène COPPIN's team) and will also integrate two new research groups: one on "intestinal neuro-immune interactions (Mr Gilles DIETRICH) and one on "intestinal barrier function: initiation and regulation" (Mr Fréderik BARREAU's team -ATIP-AVENIR request). A research laboratory space has been requested in the next CPER (Contrat de Projets Etat Région) to move onto the Langlade site, to have access to Langlade core facilities, and to gain visibility and accessibility.

Unit workforce Number as at 30/06/2014 Number as at 01/01/2016

	Doctoral students	11
	Theses defended	13
	Postdoctoral students having spent at least 12 months in the unit	22
	Number of Research Supervisor Qualifications (HDR) taken	6
	Qualified research supervisors (with an HDR) or similar positions	17	19
	SVE1_LS6 Immunologie, microbiologie, virologie, parasitology
	SVE1_LS4 Physiologie, physiopathologie, biologie systémique médicale
	Unit workforce
	Unit workforce	Number as at 30/06/2014	Number as at 01/01/2016
	N1: Permanent professors and similar positions	8 (3.2 FTE)	12 (5.4 FTE)
	N2: Permanent researchers from Institutions and similar positions	14	16
	N3: Other permanent staff (without research duties)	15 (10.8 FTE)	16 (11 FTE)
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	N5: Other researchers (Emeritus Research Director, Postdoctoral students, visitors, etc.)	11	7
	N6: Other contractual staff (without research duties)	7 (6.8 FTE)	6
	TOTAL N1 to N6	55 (45.8 FTE)	57 (45.4 FTE)

The president of HCERES "countersigns the evaluation reports set up by the experts committees and signed by their chairman." (Article 8, paragraph 5)

The evaluation reports "are signed by the chairman of the expert committee". (Article 11, paragraph 2)


Evaluation report

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

The assessments contained herein are the expression of an independent and collegial deliberation of the committee. IPAG results from the merging on January 1 st , 2011 of two research units: LAOG (Laboratoire d'Astrophysique de l'Observatoire de Grenoble), and LPG (Laboratoire de Planétologie de Grenoble). LAOG and LPG were created 30 years and 10 years respectively before the merging, both from very small initial groups. IPAG is located on the UJF campus, hosted in three buildings separated by approximately 200 m. They are next to the IRAM (Institut de Radioastronomie Millimétrique) building which hosts the French-German-Spanish institute operating two international major facilities located in "Plateau de Bure" and in Spain, and which is the other astronomical institute in Grenoble (albeit with a specific, international status).

Unit name:

Management team

Director: Mr Jean-Louis MONIN; Deputy directors: Mr Jérôme BOUVIER and Mr Sylvain DOUTÉ.

Technical director: Mr Étienne Le COARER. 2  Overall assessment of the unit Global assessment of the unit IPAG is a top-level laboratory for astrophysics and planetary sciences in France. Impressive scientific results have been obtained since the last AERES visit, thanks in particular to the exploitation of major space and groundbased facilities such as ALMA, IRAM, Planck, Herschel, VLT, HESS, Fermi, etc., and to the development of theoretical models to interpret these data. The laboratory also had major contributions in instrumental developments such as SPHERE, PIONIER, Rosetta/Consert, etc. which are now providing exciting data and are promises for great scientific achievements in the next few years. These successes are due both to an adequate strategy developed in the past and to the excellence of many individual staff members, both from the research teams and from the technical group. IPAG visibility at national and international levels is very good; there is however, given the excellence of the scientific results, room for some improvement in a few areas, in particular with respect to the U.S. community.

HCERES nomenclature

ST3 (Earth and Universe sciences)

Unit workforce

Unit workforce

A new director for IPAG will be appointed in 2015, and the nomination process had just started before the visiting committee; the committee had the opportunity to interview the prospective director. This move should not affect the future scientific strategy, which the committee found to be sound, but will certainly have an effect on the general organization of the unit. The committee was able to assess the general philosophy of the proposed management scheme and found it appropriate, but did not consider the details of the reorganization that are likely to change.

Strengths and opportunities in relation to the context

The strength of IPAG relies first on the high quality of the staff, on the quality of the scientific results, and on the technical achievements. The number of publications in refereed journals is large (more than 1000 over the reference period, i.e. more than 3 publications per permanent researcher per year), and their quality is high as well. The arrival of Rosetta on the comet, the first light of SPHERE were major events for the international scientific community in which IPAG played a key role. The strength of the technical group relies in part on long-term R&D activities that enabled the proposal, approval and realization of cutting edge instruments.

IPAG also benefits from a high quality scientific environment in Grenoble. The current reorganization of the universities, the creation of a research pole PAGE (Physique des Particules, Astrophysique, Géosciences, Environnement) will help developing and strengthening relations in the high energy and astroparticle domain. The creation of a "student spatial centre" in Grenoble is another opportunity that IPAG must grasp, with a careful monitoring of human resources devoted to this project, though. The successes of two LabEx projects (OSUG@2020 and FOCUS) guarantee some resources on the long term, which partly alleviate the reduced funding via ANR. The age distribution of IPAG staff is also wealthy, and retirements should not be a major problem in the medium term, even if some departures will occur and may have significant effects. In addition, the FOCUS LabEx is a tool for strengthening the coherence of the R&D activity, and will certainly enable stronger links with the Service d'Astrophysique of CEA in Saclay and with CEA/LETI in Grenoble.

The merging of LPG and LAOG occurred 4 years ago and can be viewed as a success, despite the difficulties inherent to this major evolution. The committee noted significant scientific interactions between the planetology group and other teams at IPAG, and the creation of a technical group has had positive effects for all teams.

Weaknesses and threats related to the context

The rapid growth of the two laboratories whose merging gave birth to IPAG seems to be over now. The management team (present and prospective) is well aware of this, but opportunities for new developments should not be neglected, however. This will require a delicate balance of ambition and realism.

The organization and management structure had to be adapted shortly after the creation of IPAG to the new size of the unit, and there is still a need to check that the present organization is well adapted to the scientific objectives and size of the unit. The committee agreed upon the scheme proposed for evolution, but this will need an active support of the IPAG staff to be implemented in a successful way, and it is not unusual that changes generate tensions. Convincing the staff of the need for such changes and their adequacy with IPAG needs will clearly be an immediate, important task of the future IPAG director.

Despite the growth of IPAG, some projects rely on very few individuals having a crucial expertise, making them quite sensitive to e.g. departures. Recruitments would solve this problem, but it is not clear that they can possibly cover all the needs.

Recommendations

-

IPAG management and staff must be ambitious, given the high scientific quality of the unit. Reinforcing the international visibility should be a priority. Several teams have the capacity to host an ERC at senior level, and applications should be encouraged;

the next major step for instrumentation for exoplanet imaging will be the planet finder for the ELT (PCS). A roadmap should be developed for attaining this long-term goal, which will include contributions to the first light ELT instruments and a careful planning of long term R&D activities;

the creation of a technical group 5 years ago, together with the creation of an instrumental team (CRISTAL) was a good move which should go further with the transformation of CRISTAL into a transverse axis, in support to scientific teams;

links with IRAM have been strengthened in the recent past, in particular with the signature of an agreement between UJF and IRAM, but they must be much more developed; all but one of the 10 researchers recently recruited at IPAG defended their PhD thesis in Grenoble. Opening the recruitments by attracting excellent external candidates would certainly be desirable, and would also help to improve the international visibility of IPAG;

the number of PhD students is still low, and the IPAG management should do its best efforts to attract them (and find the corresponding funding).

  , Observatoire de Paris (representative of CNAP) Ms Carine BRIAND, Observatoire de Paris (representative of CoNRS) Mr André CHARDIN, Université Paris-Sud Mr David CLARY, Oxford University, United Kingdom Mr John Kirk, Max-Planck-Institut für Kernphysik, Germany Mr Marc OLLIVIER, Université Paris-Sud Mr Francesco PALLA, Osservatorio Astrofisico di Arcetri, Italy Mr Cyril SZOPA, Université Pierre-et-Marie-Curie (representative of CNU) Scientific delegate representing the HCERES: Mr Michel BLANC Representative(s) of the unit's supervising institutions and bodies: Mr Jean BRAUN (Director of Doctoral School n°105, ED TUE) Mr Alain CARTELIER, UJF Mr Johann COLLOT (Director of Doctoral School n°47, ED Physique) Mr Christian COMMAULT (Director of Doctoral School n°220, ED EEATS) Mr Olivier LAMARLE, CNES Mr Denis MOURARD, CNRS/INSU Mr Francis ROCARD, CNES Mr Jérôme VITRE, CNRS/DR11 1  Introduction History and geographical location of the unit

Unit workforce Number as at 30/06/2014 Number as at 01/01/2016

	Doctoral students	29
	Theses defended	25
	Postdoctoral students having spent at least 12 months in the unit	2
	Number of Research Supervisor Qualifications (HDR) taken	6
	Qualified research supervisors (with an HDR) or similar positions	38	35
		Number as at	Number as at
		30/06/2014	01/01/2016
	N1: Permanent professors and similar positions	34	32
	N2: Permanent researchers from Institutions and similar positions	24	23
	N3: Other permanent staff (without research duties)	36	34
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)	2	2
	N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.)	15	4
	N6: Other contractual staff (without research duties)	8
	TOTAL N1 to N6	119	95


president Michel Cosnard

Stéphane Robin

3

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:

Unité Sensométrie et Chimiométrie

Unit acronym: USC

Label requested:

Current number: The "Unité de Sensométrie et Chimiométrie (USC)" has been working for more than 20 years in conceiving, developing and promoting statistical methods applied to sensometrics ans chemometrics. It is situated on the ONIRIS campus de la Géraudière mostly involved in food and food processing.

Management team

The unit has been led by Mr El Mostafa QANNARI up to the end of 2015. Since January 1 st , 2016, the management is overtaken by Ms Évelyne VIGNEAU.

HCERES nomenclature

ST1-Mathématiques

Scientific domains

Statistical methods applied to sensometrics and chemometrics.

Unit workforce

Global assessment of the unit

The unit's scientific production is very coherent and focused on its two applications fields, which is consistent with both its institutional position and its size. The members of the unit have a very good notoriety in their field, both at the national and international level. Due to the nature of its research, the unit also has strong interactions with various international partners. The scientific production is important with respect to size of the unit, mostly in journals of interface (senso-and chemometrics).

To summarize, the unit fits very well in its academic and industrial environment. The evaluation criteria which would be those of a unit of mathematics or statistics are to be modulated accordingly.

Strengths and opportunities in the context

Thanks to the coherence of the scientific activity and its long-term experience in sensometrics and chemometrics, the unit is one of the best statistical groups involved in this application field at the national level, and highly competitive at the international level. It also responds perfectly to the training needs.

Openings to new areas, such as -omics (more specifically metabolomics) and high-throughput phenotyping are considered by the unit and constitute good opportunities for the unit as they respond to a real need at the present time and because the adaptation of the methodologies developed by the unit to this new kind of data seem feasible with a reasonable effort. In the same vein, the analysis of preference and rank data is also a speciality of the unit, which has become very popular again in the recent years. The network of interactions and collaborations at the national and international level both with academic and industrial partners that has been developed by the unit along time make it in a good position to contribute significantly.

Weaknesses and threats in the context

The scientific production of the unit mainly borrows techniques from exploratory multivariate data analysis (PCA, LDA, PLS, multi-table analyses, etc.). From a mathematical point-of-view, this mostly relies on a strong expertise in linear algebra, with few random ingredients, as opposed to a vast part of statistical techniques. This makes the production very coherent, but may also contribute to a scientific isolation with respect to the rest of the statistical community. Even modest openings to more general techniques from classical statistics (e.g. model based clustering, mentioned in the unit's report) or machine learning (CART, Lasso, also mentioned) would be more than welcome. Parallel to this, research interactions with the university seem a bit weak.

The main risk for the unit within the next contract will be the renewal of its members in view of the preservation of its scientific activity. In the next 5-10 years, several of its members will get retired within a short period of time. The expertise of the unit obviously responds to a need, which could get lost then. This point needs to be addressed pretty soon, both by the unit and by the institutions it depends on.

Recommendations

strengthen its scientific position at the interface between statistics and senso-and chemo-metrics. Reinforce its scientific investment in a series of new scientific tracks such as high-throughput phenotyping, -omics data and subjects having a second youth such as preference data analysis. The development of one main package dedicated to senso-and chemo-metrics gathering a series of methods developed by the unit could also help to comfort this position;

broaden the scope of the statistical techniques mastered by the unit. Increase the number of publications in regular statistical and/or mathematical journals and increase interactions with the university. The last two points will help to increase the notoriety of the unit in the French academic community and can make it more attractive for future recruitment;

address the question of the renewal of the unit. This has to be considered in close connexion with the institutions in charge (ONIRIS and INRA).

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

	professors and similar positions	5	5
	N7: PhD students	2
	TOTAL N1 to N7	9

N2: Permanent researchers from Institutions and similar positions N3: Other permanent staff (technicians and administrative personnel) 2 2 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)

Qualified research supervisors (HDR) or similar positions Unit record From 01/01/2010 to 30/06/2015

  USC is a small statistical unit involved in the development of statistical methodology in sensometrics and chemometrics, with a special emphasize in applications to food science.

	PhD theses defended	10
	Postdoctoral scientists having spent at least 12 months in the unit
	Number of Research Supervisor Qualifications (HDR) obtained during the period
	2  Overall assessment of the unit
	Introduction


 Introduction History and geographical location of the unit

The CMIE Laboratory is a "one-team unit" jointly affiliated with the Nantes University (Faculty of Medicine) and Oniris (Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering, EA 4644). The CMIE Laboratory is also an INRA "under-contract" unit (Animal health department, USC 1383).

Initially created for the study of type 1 diabetes (T1D) pathogenesis, prevention and treatment (possibly by beta-cell replacement), the unit -under the direction of Mr Jean-Marie BACH -kept the T1D autoimmunity expertise and developed other fields such as: 1) the renewal of destroyed beta cells using hematopoietic or hepatic progenitors; 2) a translational research program on the use of spontaneous canine tumors for human cancer research, which led to the creation of a separate unit; 3) graft immune protection; 4) immune therapeutic approaches; and 5) identification of biomarkers for T1D.

The unit research activities are currently centered on three recent themes on T1D:

1) the role of the autonomous nervous system in the control of the autoimmune reaction;

2) the role of beta-cell-derived microRNAs in the autoimmune process and research of new biomarkers of the disease;

3) development of bio-artificial pancreas and xenogenic cell therapy (with the creation of the start-up Xenothera).

Management team

The head of the unit is Mr Jean-Marie BACH. He is assisted by a coordination committee composed of Mr Jean-Marie BACH, Ms Steffi BÖSCH, Ms Lucy CHAILLOUS, Ms Julie HERVÉ, Ms Blandine LIEUBEAU, Ms Mathilde MOSSER, Mr Grégoire MIGNOT.

HCERES nomenclature

SVE1_LS4 Physiologie, physiopathologie, biologie systémique médicale

Scientific domains

The unit research activities are centered on three recent research programs on type 1 diabetes. They range from preclinical research using spontaneous/transgenic mouse models of diabetes or pigs to human research. The current axes were initiated at the time of the previous evaluation and one new recent project:

1. role of the autonomous nervous system in the control of the auto-immune reaction, including a new project emerged in 2014 on the role of stress in the control of immune responses in pig; 2. beta-cell-derived exosome-associated microRNAs: role in the autoimmune process and potential significance as new biomarkers of diabetes (human, dog); 3. development of a bio-artificial pancreas (macroencapsulated islets from piglet or human).

Unit workforce

Introduction

The CMIE lab is a "one-team unit" jointly affiliated with the Nantes University (Faculty of Medicine) and Oniris (Nantes Atlantic College of Veterinary Medicine, Food Science and Engineering) (EA 4644), and is an INRA "undercontract" unit (Animal health department, USC 1383).

From 2004 to 2011, under the direction of Mr Jean-Marie BACH, the CMIE unit (single-team unit) studied diagnostic and therapeutic approaches for type 1 diabetes (T1D) and strategies for beta-cell replacement. During this period, the CMIE unit also initiated a translational research program on the use of spontaneous canine tumors for human cancer research that ended in 2012 with the creation of a new ONIRIS research unit (AMaRoc).

The unit research activities are now centered on three recent research programs on T1D. They range from preclinical research, using spontaneous/transgenic mouse models of diabetes or pigs, to human research. The current axes were initiated at the time of the previous evaluation and there is one new recent project:

1. role of the autonomous nervous system (ANS) in the control of the autoimmune reaction, including a new project emerged in 2014 on the role of stress in the control of immune responses in pig; 2. beta-cell-derived exosome-associated microRNAs: role in the autoimmune process and potential significance as new biomarkers of diabetes (human, dog); 3. development of a bio-artificial pancreas for T1D patients (macroencapsulated islets from pigglet or human). This project also led to the creation of the start-up Xenothera (www.xenothera.com).

While these projects emerged during the previous evaluation period (2010)(2011)(2012)(2013)(2014)(2015), they have led to a refocusing of the unit research on better-selected topics with the highest potential impact. In particular, previous projects on autoreactive CD8+ T cells, myeloid-derived suppressor cells, role of heme oxygenase and carbon monoxide, implication of Cxcr1 in T1D and beta-cell replacement using hematopoietic or hepatic progenitors are not further pursued. This seems a wise decision in the current landscape of increasing research competition and may increase the scientific yield of the team in the long term. For all the themes presented, this refocusing effort should be further pursued to fully dissect the ambitious hypotheses put forward and improve the publication targets. Despite major improvements in this sense, all themes still suffer from an excessive dispersion of scientific questions and models.

The past production on these subjects is of moderate impact. The future programs are of heterogeneous impact. Despite the remaining weaknesses, the unit seems to have evolved in a promising direction as compared to the previous evaluation. In particular, the integration into the ECTIS IHU is a major improvement towards increased visibility, with ongoing collaborations that have already produced one high-impact publication (J Clin Invest 2015).

Global assessment of the unit

The CMIE lab is a "one-team" unit, with a strong pre-clinical expertise in T1D, highly integrated in the Oniris Veterinary Medicine College, the INRA Animal Health Department and the Nantes Faculty of Medicine. This allows unit members to propose a research program with good translational potential and in line with the "One health, One Medicine" concept, i.e. integrating scientific questions addressed to both human and animal health with productive exchanges between the two. The research staff has a mixed educational profile (veterinary, pharmacist, medical doctor and scientific), providing diversified expertises, and a good ratio of Researchers/Engineers-Technicians. The unit features strong collaborations at the regional level, while national and international collaborations and visibility are more limited at present. The unit seems well managed by a dynamic director and has an important involvement in teaching duties. The past programs on HO-1 and T1D have led to some good impact publications. If the total number of publications compared to the previous evaluation period is roughly similar, publications in leader positions are more limited (10 out of 23 in the last 5.5 years), but this decrease is somehow offset by a few excellent publications. These last years, the unit has consolidated its expertise in T1D, and the refocusing of efforts on more selected topics may improve the publication performance in the future. They have contributed to the creation of one start-up. They have had limited success in fund raising and personnel recruitment, of Post-docs in particular. They had to face the departure of a key young staff, but, fortunately, benefit from the recruitment of two young assistant professors and the future arrival of two senior professors among which one has clinical veterinary duties, which opens new possibilities for studying diabetes and obesity phenotypes in outbred dogs. One technical staff member is retiring this year but will be replaced. The unit presents a project well balanced in terms of task force repartition and ranging from fundamental research to therapeutic approaches. However, future themes are of heterogeneous impact and robustness, and the justification of some WPs in the 3 research themes proposed is debatable.

Strengths and opportunities in the context

There is an integrated "One Health, One Medicine" approach to research, with a good cross-talk between human and animal investigations and translational profiles.

There is a broad complementarity of education and expertise of the staff (veterinary, pharmacist, medical doctor and scientific).

There is a dynamic management and team life.

The proximity of the Veterinary School favours the development of animal models of veterinary and/or medical importance.

The unit is excellently integrated into a local network of collaborations (notably with the IHU ECTIS).

There are good collaborations with non-academic partners (themes 1 and 3).

Additional permanent staff has been recruited (2 assistant professors, themes 1 and 3).

There is expertise in preclinical T1D (murine models, human), and opportunities are offered with the relevant and less competitive pig and dog models.

The unit hosts a biocollection of T1D PBMC samples within the GOFEDI network.

The unit has created a niche in the miRNA domain (and particularly in exosome-associated miRNAs) in T1D.

Another niche is represented by pig and pet experimental models.

The unit has gained expertise in ANS-immune system crosstalk.

There is a synergy with the Xenothera start-up, which offers funding opportunities for the unit (contract, Cifre).

There is good technology transfer potential, with 2 patents already filed.

An "Animal Immunomonitoring" platform has been created, which may attract additional academic and industrial partnerships.

There is an excellent involvement in teaching at the master and doctoral levels, including in summer schools.

The level of publications is improving.

Weaknesses and threats in the context

National and international collaborations and visibility are limited.

There has been limited success in fundraising, and no funding from international agencies.

Theme 2 has no funding at present. Participation to international meetings is poor.

There are difficulties in recruiting non-permanent staff at the postdoctoral level.

The number of PhD students over the past years (and associated publications) has been limited.

Scientific animation on-site is limited.

A talented assistant professor strongly involved in theme 1 has left the unit.

There is strong competition on theme 1.

The staff members display a heterogeneous level and impact of publications, with a limited number of articles in key authorship positions.

The rationale for some WPs in the research themes does not rely on solid preliminary data and/or hypotheses.

There are technical hurdles associated with some themes.

Research efforts are somehow dispersed on several challenging questions, making the overall project overambitious.

Scientific crosstalk among themes is limited.

Recommendations

-develop a national and international network of collaboration ; -increase funding, including international agencies ; -iImprove recruitment of postdoctoral researchers ; -improve scientific animation onsite by more regular scientific meetings within the unit and by organizing seminars by invited speakers ;

-capitalize on the opportunities offered by Oniris and local collaborations, e.g. use of pig/dog models and expertise on neonatal pig islets ;

-refine some WPs of the research themes by refocusing theme on the basis of solid preliminary data and funding opportunities.

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

	professors and similar positions	3	6
	N2: Permanent researchers from Institutions and similar positions	3	3
	N3: Other permanent staff (technicians and administrative personnel)	6	6
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)	1
	N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.)	1
	N6: Other contractual staff (technicians and administrative personnel)
	N7: PhD students	1
	TOTAL N1 to N7	15
	Qualified research supervisors (HDR) or similar positions	2
	Unit record	From 01/01/2010 to 30/06/2015
	PhD theses defended	2

Postdoctoral scientists having spent at least 12 months in the unit 1

Number of Research Supervisor Qualifications (HDR) obtained during the period


Jean-Marie Bach

M Peter

Van Endert

M Jerome Alexandre

Ms Nathalie Chaput

Aeres Scientific

Ms Ana-Maria Lennon-Dumesnil

M Alain Chauvin

The site visit took place on February 15, 2011 between 3 pm and 6 pm. The unit was presented in a room of a biomedical center of the University hospital Nantes, thus the premises of the unit were not inspected by the commission. The presentation was organized in an initial presentation of the history, environment, structure and project of the unit by its director, followed by presentations of the two main projects (type 1 diabetes and autonomous nervous system, miRNAs in beta cells and type 1 diabetes. After a discussion, the jury split in three parts and met permanent staff scientists, technicians and students in parallel. The visit ended with a short closed discussion among jury members.

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

This unit is the successor to a research unit founded in 1979 at the Faculty of Medicine of the University of Nantes.

The unit obtained co-accreditation by INRA in 1992 and become -after having moved to the Veterinary College of Nantes in 1994 -an UMR INRA/University/Veterinary College (UMR_A) in 1998. Recently, the Veterinary College merged to an agricultural engineering school to become the ONIRIS entity. The principal activity of the unit has always been related to diagnostic and therapeutic approaches for type 1 diabetes, including an interest in strategies for beta cell replacement. Next to this, the unit has had a strong and consistent implication in teaching for students of the Veterinary school. Following previous reviews organized by INRA in 2005 and2007, the unit undertook a restructuring and refocusing in 2006, under the directorship of its present director. In the application presented, the unit undertakes an additional round of refocusing, shedding on the occasion the majority of its researchers with teaching duties while retaining most technical staff and all other researchers. The unit also will change affiliation and be affiliated as UMR_MA with the University of Nantes and the recent created ONIRIS entity (formed by a merger of the Veterinary school with an agricultural engineering school) associated with an USC INRA.

 Management team

The unit is directed by M. Jean-Marie BACH (ONIRIS). Unit governance involves a number of committees in charge of quality control, hygiene and security, scientific animation, rodent facilities, metrology, and an immunomonitoring platform. An executive committee (5 members) and a unit council (all unit members) decide on various matters. Globally this is a well-managed unit using efficient local networking that continues a thematic and personnel restructuring started 5 years ago. The results obtained during the previous mandate were of heterogeneous quality. Projects related to CD8+ T cell epitope discovery in type 1 diabetes showed a good productivity resulting in publications with good impact and citation rates, while 3 other projects produced limited results of low impact. "Incubation" of a now independent group dedicated to establishing pet models for human cancer is an additional notable result. The project lists three lines of research two of which appear well structured while the third is still "under construction" and lacks adequate funding and staff to be arranged in collaboration with the local IHU initiative. The first project aims to produce tolerogenic antigen-presenting cels using ß2-adrenergic stimulants. While some data suggesting an effect of these reagents on Antigen Presenting Cells (APCs) are presented, data showing that these reagents protect from diabetes are not yet available. It will be important to focus on obtaining this evidence to confirm the relevance of this potentially important project as a therapeutic approach for type 1 diabetes. The second project will examine micro RNAs as immunostimulatory and gene-silencing reagents in diabetes. This project is supported by some interesting preliminary data and has the potential to develop into a cutting-edge program. The programmed experimentation is highly ambitious and represents significant risks with respect to competition, technical challenges, funding, and staff expertise.

 Staff members

 Strengths and opportunities

-Efficient unit management ;

-Expertise in research using the Non Obese Diabetes (NOD) model and lymphocytes from type 1 diabetes patients ;

-High potential specifically of project 2 ;

-Adaptation of project 3 to specific environment and specifc expertise ;

-Interesting local collboration in project 3.

 Weaknesses and threats

-Technical and scientific challenges for staff due to recent re-orientiation ;

-Limited availablity of most scientists due to teaching duties, with imbalance scientists vs. technicians and engineers ;

-Dearth of post-docs and tenured researchers without teaching duties ;

-Uncertainty with respect to clinical relevance of project 1 ;

-Strong competition in project 2 ;

-Uncertainty with respect to manpower and funding for project 3 ;

-Globally limited success in fund raising.

 Recommendations to the head of the research unit -In project 1, focus on rapidly confirming therapeutic and/or prophylactic efficacy of ß2-stimulants in the NOD model ;

-Seek collaboration with teams with confirmed expertise relevant for project 2, which could also be helpful for fundraising ;

-Benefit from specific strengths, opportunities and environment in developing project 3 ;

-Enhance efforts to obtain funding and recruit postdocs and tenured researchers without teaching duties. 3  Specific comments

 Production results

A1

 Appreciation on the results

During the last 4 years, unit researchers have been involved in 5 projects. The results with the greatest impact were obtained in project 1, autoreactive CD8+ T cells and their controls. Efforts to discover CD8+ T cell epitopes were quite successful and allowed for publication of several papers with good impact and citation rates. In addition, there is an ongoing project in which CD8+ cells from pancreas graft recipients are monitored for phenotype and function, but few or no results seem to be available yet. Moreover, inital results concerning miRNAs were obtained in this context (see below). A second project dealt with reagents rendering dendritic cells tolerogenic. A number of results were obtained with heme oxygenase 1, however this research was apparently abandoned for reasons that are not spelled out, and the investigators switched to using ß2-adrenergic stimulation for DC « conditioning ». Two more long-standing projects related to myeloid-derived suppressors and to transduction of hepatocytes with the aim to generate insulin-producing cells were continued but seem to have produced little remarkable results in the period. A fifth project, thematically set apart from all other projects, had the aim to set up pet animal models for human mammary cancers and B cell lymphomas. The unit is obviously well placed to develop this project which has been able to attract good funding.

Having been « incubated » by the unit for several years, the pet cancer project carried by several unit researchers has given rise to an independent group that will not be part of the unit in the future. In summary, the unit has studied a large number of projects, however the main impact and originality of the research concerned discovery of epitopes derived from type 1-diabetes autoantigens, while other projects were either little productive or produced preliminary results that are the foundation for the project (see below). Incubation of a promising pet cancer group is another significant result.

Unit scientists have published a total of 13 publications in the first or last author positions over the last four years.

Another 10 publications are co-authored. Consistent with what is said above, the highest (good) impact was obtained for epitope discovery studies, while other publications tended to have low impact (less than 5 citations). All but one of the researchers are publishing according to AERES criteria. Unit scientists made 11 oral or poster presentations at international meetings and some more at national ones. According to the application, publication activity has increased by 40% relative to the previous 4-year period. Six students defended their thesis during the period.

The unit is very well integrated in a local network of partnerships. These include the entity produced by the fusion of the veterinary and engineering schools (ONIRIS), the University of Nantes and three local INSERM units. The unit is also part of a local IHU (Institut Hospitalo-Universitaire) project focusing on transplantation in which it will focus on development of pigs as organ donors.

 Appreciation on the impact, the attractiveness of the research unit and of the quality of its links with international, national and local partners Units scientists did not receive awards in the period concerned. There were no invitations to speak at international conferences. One unit member was invited to chair a session at the EASD meeting 2005 in Athens.

The unit has not been able to recruit high level scientists or postdocs in the period under consideration. One energetic young scientist with teaching duties employed by ONIRIS was recruited to the unit. This scientist will take a leading role in one of the two principal projects in the future, making this a successful recruitment.

Unit leaders have been moderately successful in fund raising over the last years. Next to recurrent lump sum fuding of 70 k€ per year, the unit has obtained a total of about 500 k€, of which 200 k€ were given from industry, University and INRA for the pet cancer project. However, the unit is fairly well equiped due to successful fund raising from regional sources. For example, a FACS Aria state-of-the-art cytometer has been purchased.

The unit coordinates a regional network for recruitment of type 1-diabetes patients and also recruits and monitors recipients of pancreas grafts. Its participation in the local IHU project implies participation in an emerging European network dedicated to developing pigs as organ donors (« European pig for medical use network »). However, this network apparently has not yet obtained funding. Collaborations with European groups in Louvain (Belgium) and Padua (Italy) are part of this network under construction.

The unit runs an immunomonitoring platform which is offered as a service to local academic and industry partners.

 Appreciation on the strategy, management and life of the research unit

This unit appears to be very well managed. The unit disposes of a variety of committees ensuring consensual planning and scientific development that involves and motivates all members. Critical tasks and reglementation requirements are taken care of by assigned members. Hygiene and safety is taken serious and a folder with rules and procedures is available to unit members. Regular scientific meetings are held. Separate discussions of jury members with the different staff categories (scientists, engineers and technicians, students) revealed a high degree of satisfaction of all members, with complete absence of dissenting voices. Even scientists who recently had to change subject, or students lacking publication, confirm being entirely satisfied by unit management.

The unit director has instaured a policy for identification and choice of scientific topics and projects. There are regular unit meetings, including journal clubs, meetings devoted to team projects, and meeetings devoted to general unit matters (twice yearly full-day).

Unit scientists are strongly involved in teaching veterinary students. Next to teaching of Molecular Physiology, they co-organize a master 2 program. Moreover, 6 PhD students and another 12 master 1 or master 2 students were trained betwen 2006 and 2010.

 Appreciation on the project

The unit proposes three main projects. Remarkably, none of these is identical to one of the five projects pursued in the previous period. Thus, the unit proposes a fairly radical scientific re-orientiation. All projects are clearly designed with a long-term perspective.

The first project follows on previous efforts to obtain tolerogenic DCs using heme-oxygenase and proposes to use ß2adrenergic stimulation to this end. Preliminary data obtained in the OT-I system are shown suggesting that these reagents modify APC function and downregulate uptake, degradation and presentation of ovalbumin. ß2-stimulants do not protect NOD mice from diabetes, however chemical sympathectomy increases disease incidence. The project is structured in three parts and proposes a number of straightforward projects aiming to assess the effect of ß2 stimulation on antigen presentation to CD8+ cells and CD4+ cells in the ovalbumin model, and on autoimmunity in the NOD model and in patient PBMC. Experiments are fairly descriptive, and truly mechanistic studies are not proposed. Tools required for the project are available (pharmacological, surgical, electrical intervention). This project is risky as no strong preliminary evidence for protection from diabetes is available. It would seem advisable to start with NOD protection experiments since the project will be of less clinical interest if such an effect cannot be shown. There is also a concern as to the practical impact of the approach, as long-term ß2-stimulation would not be without side effects in the clinic.

The second project concerns micro-RNAs in type 1 diabetes. These miRNAs are known to have both immunostimulatory and gene silencing effects. A preliminary screening revealed that two miRNAs (503 and 877) were reduced in serum from NOD mice. On the other hand, miRNA 29b induced secretion of type I interferon from DCs in vitro and in vivo, and protected mice from diabetes upon transfer of CD8+ T cells recognizing beta cell-expressed hemagglutinin in a transgenic model. Thus, the underlying hypothesis here is that miRNAs might be of interest both as diagnostic and as therapeutic tools in diabetes. An ambitious program is proposed that aims to 1) determine a diabetes-associated miRNA fingerprint (both in the NOD model and in patients), 2) identify the cellular source of miRNAs with altered expression in T1D, 3) evaluate immunomodulatory effects of miRNAs. Here a particularly ambitious program is formulated that includes analyzing effects on APC subtypes by various methods, studying effects of miRNAs released by apoptotic cells, examining mice with a global deficiency of miRNAs (Dicer k.o.), and identify targets of miRNAs of interest. This project is potentially of high interest and certainly innovative, however it is associated with a number of risks that include strong competition in the field, technical challenges, possibly insufficient funding, and an overly ambitious wide-ranging program.

The third project is to be developped in collaboration with the IHU project team at the University of Nantes.



  Date and execution of the visit:

  : Number of permanent researchers with teaching duties (recorded in N1) who are active in research 6 A2: Number of permanent researchers without teaching duties (recorded in N2) who are active in research 1 A3: Ratio of members who are active in research among staff members [(A1 + A2)/(N1 + N2)] 0.875 A4: Number of HDR granted during the past 4 years 2 A5: Number of PhD granted during the past 4 years 6

Sciences du Vivant et Environnement

	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%
	*

Aim 1 concerns development of immuno-protected (encapsulated) pig islets. The strategy employed is apparently already being developped commercially by a New Zealand-based company, and it would have been good to spell out what specific aspects, competitive advantages or industry perspectives relative to that company are present in Nantes that justify this project. A second aim concerns development of the « European pig for medical use », a project under construction, as discussed above. Overall the third project seems to be in its planning stage as funding is not yet

Statistiques de notes globales par domaines scientifiques

(État au 06/05/2011)

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

available and staff is not clearly assigned. This project is evidently particularly consistent with the specific environment of a research unit at a veterinary school.

The unit has a policy for assigning staff to projects. Staff assigned to each of the two main projects is clearly identified (3.5 full-time equivalents for project 1, 3.2 for project 2).

All projects of the unit are fairly original and explore recent fields and therefore have the potential to be « cutting edge ».


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:

Unité

 Introduction

The "Unité de Recherche Translationnelle sur le Cancer en Normandie" is a multi-team project that is proposing to regroup several existing units around a new project. The project is truly multi-disciplinary with epidemiology and biostatistics, imaging, animal models, preclinical biology, chemistry and radiochemistry. Efforts will be centered on 2 main axes: cognitive function in the context of cancer treatment and advanced ovarian cancer treatment.

History and geographical location of the unit

The future center comprises four teams: two are affiliated with University of Caen and Inserm and are located in the Cancer Center François Baclesse (UMR1086 headed by Mr Guy LAUNOY, and the more recent UMR1199 "Bioticla" headed by Mr Laurent POULAIN); two originated from UMR6301, headed by Ms Myriam BERNAUDIN, affiliated with CEA, CNRS and University of Caen and located about 1km apart in the Cyceron environment.

Management team

The center will be headed by Mr Guy LAUNOY and the deputy director is Ms Myriam BERNAUDIN.

HCERES nomenclature

Principal: SVE1_LS7 Secondary: SVE_LS4 SVE_LS5 ST4

Scientific domains

The project includes epidemiology and biostatistics, imaging, animal models, preclinical biology, chemistry and radiochemistry. 2  Overall assessment of the interdisciplinary unit

Unit workforce

Introduction

The 4 existing units are merging around a new project. The project is truly multi-disciplinary with epidemiology and biostatistics, imaging, animal models, preclinical biology, chemistry and radiochemistry.

The team "Cancers & Preventions" UMR1086 Inserm-UNICAEN covers a large domain of cancer epidemiology, from public health to clinical research. In order to investigate cancer risk factors, and in particular those associated to agriculture and to asbestos exposure, it sets and follows cohorts, including the largest cohort of farmers in the world (AGRICAN). The follow-up of AGRICAN, via the MSA ("Mutuelle Sociale Agricole"), a complementary health insurance dedicated to farmers, guarantees an almost exhaustive long-term follow-up of this large cohort. This cohort is included in the very structured international collaborative network AGRICOH, which is an additional guaranty for future results of high quality standards. Other cohorts allowed demonstration that asbestos environmental exposure is associated with several digestive cancers and further exploration will be possible through the international network on mesothelioma under the team coordination. In secondary prevention, the demonstration, during the previous contract, that the immunochemical faecal occult blood test is best suited for screening for colorectal cancer has been very innovative, and is now nationally implemented in France. Unit members have recently conducted further work to identify the best immunological test, and further collaborations are ongoing to develop screening procedures for lung cancer in persons at risk. A new area of research, concerning tertiary prevention, is survivorship, and in particular the decrease of cognition associated with brain cancer treatment. Interestingly, some clues for a role of angiogenesis have generated the first collaboration with team 3 (LDM-TEP).

The team CERVOxy "Hypoxia, cerebrovascular and tumor pathophysiology" (constitutive team of UMR 6301-CNRS-CEA-ISTCT UNICAEN), has an expertise in the field of hypoxia and cerebral pathologies, and particularly ischemia and brain tumors. As a general matter, the objective of this team is to develop new preclinical models pertinent for the clinic, to develop a new therapeutic strategy focusing on hypoxia, and to propose and develop new biomarkers using MRI and TEM imaging (MRI, TEP), permitting to better target and to short term evaluate treatments of cerebral pathologies. It investigates the impact of hypoxia in the treatment of brain tumors, in particular the role of erythropoietin in the growth of glioma and its resistance to treatments. The work done is clearly highly original and often inter-disciplinary in nature. The team has established a niche with nice models for research concerning imaging of the brain in small live mammals and patients, as well as the emerging use of a novel animal model based on marmosets that they are beginning to exploit.

The team LDM-TEP "Methodological Developments in Positron Emission Tomography "(team constitutive of the UMR 6301 CNRS-CEA-ISTCT-UNICAEN) is centered on the development and evaluation of radiopharmaceuticals for PET imaging, rather than the development of PET technology per se. These developments in radiopharmaceuticals for clinical imaging are focused on Alzheimer's disease, psychiatry, and oncology. The team has established a very specific and desirable expertise in radiochemistry (C11, Fluorine 18, Gallium 68) and in the development of radiotracers (automated radiosynthesis, in vivo evaluation, POC) with an activity of production of radiopharmaceuticals for PET imaging (investigational medicinal products, programmed production, clinical trials). About 20% of the activity is dedicated to service production of radiopharmaceuticals and 80% is dedicated to research. More than 500 patients have been treated with radiopharmaceuticals produced by the team since 2010.

The team BIOTICLA "Biology and Innovative Therapies of Locally Aggressive Cancers", Inserm UMR 1199 UNICAEN, is positioned in the field of ovarian cancers, with two themes: pharmacological modulation of apoptosis and role of miRNAs, in the response to treatment or as biomarkers. This team is conducting world-leading research in evaluating Navitoclax, a BH3 mimetic, in ovarian cancer. This team is the first having shown that Navitoclax has single agent activity in ovarian cancer and collaborates with Abbvie, the pharmaceutical company behind this BH3 mimetic. The team works also on biomarkers to identify patients likely to respond well to Navitoclax, on inhibitors of Mcl-1, which endows resistance to Navitoclax, and on the identification of the intracellular signalling pathways that may be pharmacologically manipulated to inhibit Mcl-1. The team is also conducting novel work to understand how miRNAs and lncRNAs contribute to drug resistance, the goal of these investigations being to identify novel therapeutic targets as miRNAs have the potential to modulate the expression of multiple genes.

During the next 5 years, collaborative research will be centered on 2 main axes: cognitive function after radiation therapy of brain metastases or brain primary cancer, and prognosis factors and treatment of ovarian cancer.

Global assessment of the unit

The unit project is truly multi-disciplinary with epidemiology and biostatistics, imaging, animal models, preclinical biology, chemistry and radiochemistry.

The evaluation committee has been impressed by the multidisciplinary aspect and the quality of the previous works and of the projects for future. As a general matter, the evaluation committee has been convinced by the interest and by the huge potential of the collaborative multi-disciplinary project of Cancer and Cognition platform, in particular given the expertise and achievements available within the various teams, and the geographic presence of France Hadron in Caen. Nevertheless, although marmoset is a nice model, the clinical impact of the research is not totally clear. It may be to the unit's advantage to establish collaboration with medical physicists, neuro-oncologists, and neuro-psychiatrist specialized in the domain.

Strengths and opportunities in the context

the development of a Cancer and Cognition platform is a true opportunity for very productive collaboration between the different teams of the unit on an issue, the cognitive decline after brain irradiation, which is one of the major issues in cancer survivorship;

the structured management of the unit and the attractiveness for academics and PhD students, which has constantly increased during the current period, has proved effective for the team success;

the location of the unit in the Centre François Baclesse, its strong interaction with the clinicians of this cancer treatment Centre, as well as the important support from this Centre, and the facilities it offers in term of team management facilities.

Weaknesses and threats in the context

the difficulty to find resources for post-docs and to attract students from other universities is somewhat a limitation;

there is a risk if preclinical and clinical strategies are not rapidly integrated into the long-term plan;

the strong association of BIOTICLA in the development of Navitoclax could force a significant portion of the team to realign its research if clinical trials are unsuccessful;

most or the publications of the unit are either as non-leading authors in high impact journals (IF>10), or as leading authors in lower-impact journals;

with the exception of the "Cancer and Prevention" team, and to a certain extent the BIOTICLA team, the other teams of the unit have too much focus on local, rather than international collaborations.

Recommendations

the team "Cancer and Prevention" should develop a strategy to make the most benefit of the interaction with other teams in term of sample selection;

patient specification for validation of biomarkers would be an asset to predict successful and optimized transfer from preliminary clinical to clinical population prognosis studies;

considering the already strong expertise of Cervoxy and Bioticla teams in biology, the LDM-TEP team should consider consolidating its expertise in chemistry and biochemistry, in order to maintain a unique edge;

the unit is encouraged to make all attempts to increase its number of post-doctoral positions;

the unit should attempt to publish in more renowned journals than is currently the case;

the unit should increase its collaboration with leading groups in Europe and the other areas of the world.

  de Recherche Translationnelle sur le Cancer en Normandie

		Ms Anne GUESDON, Université de Caen
		Ms Christine GUILLARD, Inserm
		Mr Frédéric MARIE, CHU Caen
		Mr Khaled MEFLAH, Centre Antoine Baclesse, Caen
		Ms Florence NOBLE, CNRS
		Mr Samir OULD ALI, Inserm
	Unit acronym:	URTCN Mr Frédéric SCHMIDT, CNRS
		Mr Pierre SINEUX, Université de Caen
	Label requested:	Inserm
	Current number:
	(2015-2016): Name of Director Heads of Doctoral Schools:	Mr Guy LAUNOY
	Name of Project Leader (2017-2021):	Mr Guy LAUNOY
	Expert committee members
	Chair:	Mr Florent DE VATHAIRE, Inserm
	Experts:	Ms Anne GALY (representative of the Inserm CSS)
		Mr Francis GUILLEMIN (representative of the Inserm CSS)
		Ms Catherine HEURTEAUX, IPMC (representative of the CNRS)
		Mr Lasse JENSEN, Karolinska Institutet, Stockholm, Sweden
		Mr Alan RICHARDSON, Institute for Science & Technology in Medicine, Keele
		University, UK
	Scientific delegate representing the HCERES:
		Mr Emmanuel LAGARDE
	Representatives of supervising institutions and bodies:
		Ms Claire GIRY, CEA
		Mr Vincent GOUJON, CNRS, DR19

Mr Patrick LEROUGE, Doctoral School n°497, EdN BISE, "École Doctorale Normande de Biologie Intégrative, Santé et Environnement" Mr Jacques ROUDEN, Doctoral School n°508, "École Doctorale Normande de Chimie (EDNC)"

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

	professors and similar positions	19 (7,36)	17 (6,7)
	N2: Permanent researchers from Institutions and similar positions	20 (14,3)	19 (14)
	N3: Other permanent staff (technicians and administrative personnel)	27 (23,7)	26 (22,7)
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)	7 (4,66)
	Unit record	From 01/01/2010
		to 30/06/2015
	PhD theses defended		22

N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.) 12 N6: Other contractual staff (technicians and administrative personnel) 26 (24,9) N7: PhD students 29 TOTAL N1 to N7 140 (116) Qualified research supervisors (HDR) or similar positions 35 Postdoctoral scientists having spent at least 12 months in the unit 10 Number of Research Supervisor Qualifications (HDR) obtained during the period 11