The CRCL is composed of around 20 teams, organized into three scientific departments, with a total of around 400 researchers, including 118 permanent researchers. The CRCL has made good progress since its inception in 2011, for example with the hosting of four new teams (two ATIP-AVENIR laureates and two laureates of the international and emergences calls in 2013). The CRCL teams benefit from direct access to rapidly developing state-of-the-art core facilities (cell sorting and cytometry platform, imaging facilities, drug discovery laboratory, animal services, and others).

Within the review period (January 2011 -August 2014), the CRCL productivity was excellent, including large numbers of publications, with 126 of these articles in journals with Impact Factors >10. CRCL researchers also filed 45 patents, of which 6 have been licensed to industry. CRCL scientists have contributed to the local environment in Lyon, including via participation in the DEVweCAN LabEx (Laboratoire d'Excellence, director: Mr Patrick MEHLEN) and the LYRIC (LYon integrated Research Institute in Cancer, director: Mr Jean-Yves BLAY, deputies: Mr Alain PUISIEUX, Mr Charles DUMONTET).

To increase its international recognition, the 1st CRCL symposium in February 2013 centred on the fundamental aspects of the biology of cancer, while linking basic, clinical and translational research. The CRCL aspires to enhance its international reputation further in the coming years. In addition, the CRCL launched a new Master in oncology. Together with international student exchange programmes, this provides clear evidence of significant contribution to training of the future generation of cancer researchers.

The CRCL is located on a unique site in Lyon which benefits from all the necessary facilities required to develop interactions between basic cancer researchers, clinical practice, education and training. Indeed, it is colocated with, or in close proximity to, the Centre Léon Bérard hospital, the Édouard Herriot hospital (HCL), the Faculties of Medicine and Pharmacology and the International Agency for Research on Cancer (IARC, a WHO organization). The 20 CRCL teams are all located within a relatively small area in Lyon, with 16 of the teams based within the Cheney A and D buildings on the Centre Léon Bérard site, 2 teams located in the Inserm building Cours Albert Thomas and two teams located at the Rockefeller and Laennec medical schools. Moreover, a new research building is under construction within the CLB site (expected delivery date mid 2014). This new building will host additional research teams from basic research in the CRCL and translational/applied clinical research.

Management team

The CRCL has been Directed by Mr Alain PUISIEUX since 2011. Mr Alain PUISIEUX is assisted by two deputy directors, Mr Patrick MEHLEN and Mr Charles DUMONTET. All three are excellent and experienced internationally renowned researchers in their own right and direct teams within the CRCL in addition to their management duties. 2  Overall assessment of the unit

HCERES

Global assessment of the unit

The cancer research centre of Lyon (CRCL) was formed in 2011 with the remit of bringing together scientists, teachers and administrators to create a centre of excellence in tumour biology, form close functional links with the local cancer treatment (hospital) centres, primarily the Léon Bérard Centre and the Hospices Civils de Lyon, so promoting clinical translation of CRCL research. The CRCL participates in teaching in both research and clinical disciplines. It is the view of the review panel that a huge amount of progress has been made on the journey to creating a comprehensive cancer centre in Lyon, and the director and his senior colleagues should be congratulated on progress to date. The environment is dynamic, with some 400 researchers, which includes 108 permanent researchers and 20 physicians, also with introduction of new groups and some excellent early career researchers during the review period. These researchers benefit from state-of-the-art facilities which are being developed rapidly in the CRCL, together with excellent scientific equipment and administrative services that create an environment persimissive for science at the very top level. Overall, the director (Mr Alain PUISIEUX) and his deputy directors (Mr Patrick MEHLEN and Mr Charles DUMONTET) should be congratulated for their vision and progress. There are some outstanding scientific groups in the CRCL; as always with review of organisations like the CRCL, there are also some groups that are less strong and require monitoring and mentoring by the director and his senior colleagues.

There are three main scientific themes in the CRCL organised into departments, in the review period these were: 1) Tumoral escape, 2) Information flow in the cancer cell, and 3) Immunity, micro-environment, virus. The high impact research outputs of each department in terms of publications and patents were considered to be excellent, and the panel noted a very large volume of papers to which CRCL researchers had contributed. Going forward, some reorganisation and team reassignment is proposed -giving rise now to three departments for the next contract period: 1) Tumour escape signalling (7 teams), 2) Cancer cell plasticity (7 teams) and 3) Immunity, virus and inflammation (9 teams). These themes are extremely relevant and important in modern cancer research, and the panel considered the proposed new organisation to be appropriate. It was noted, and considered important, that there was significant collaboration and exchange between teams within departments and between departments, and future joint publications were expected to reflect excellent team science that provided added value in the future. It was welcomed that the departments were provided with some resources to promote meetings, seminar series and facilitate inter-team interactions. The CRCL management team, committees, working groups and dedicated heads of core facilities all generate a professional environment for optimising science and the smooth running of the CRCL.

The panel commends: 1) the contribution of CRCL scientists to the award and success of the LabEx (DEVweCAN; dir: Mr Patrick MEHLEN) programme, which is to study developmental processes in oncogenesis and which involves several CRCL teams, and 2) the contribution of senior members of CRCL staff to the formation of LYRIC (dir: Mr Jean-Yves BLAY) which brings together lab-and hospital-based researchers from around Lyon so as to integrate basic science with clinical/translational opportunities. The panel considers that both of these 'structures' are very important to the ambition of creating a comprehensive cancer centre that will ultimately integrate cancer research and treatment in Lyon. The CRCL involvement in both the LabEx programme and LYRIC appear to be successful. Due consideration needs to be given to how the funding associated with these, in particular DEVweCAN, may provide sustainable longterm value to the overall comprehensive cancer centre ambition once the particular tranche of funding ends.

The ambition to be world class requires that the international reputation and visibility of the CRCL teams is consolidated, and enhanced in the longer term. Multiple approaches to ensure this are wise, and the Director and deputy directors are aware of these. More EU, ERC, H2020 etc. funding applications should be encouraged, and endeavour and funding dedicated to travel to increase invited speaker invitations at key international meetings should be considered a high priority. However, the panel did note that several international scientists had been recruited during the review period. Those who had been recruited via rigorous external assessments were generally considered to be excellent, especially the early career researchers. However, the panel urged that such rigorous Principal Investigator (PI) appointment criteria and assessment was carried out for all appointments, including internal promotions to PI/team leader, to ensure that the future research leaders within the CRCL will all be of the highest quality. The panel was very positive about the Scientific Advisory Board (SAB) and urged the director to ensure that they were fully engaged in providing crucial advice, particularly in making new appointments and internal PI promotions.

The overall perception of the review panel was that outstanding science and excellent clinical/translation was being performed by more established ('senior PI') groups, and that there had been an influx of outstanding talent amongst the externally recruited 'younger' groups; however, the standard of some 'mid-career' and internally promoted PIs was not universally as high. This is something the director and his deputy directors need to focus on going forward and perhaps introduce some mentoring and review with respect to their scientific strategy, productivity and presentations of those groups.

The researchers in the CRCL are extremely commercially-aware; it was noted that very many patents had been filed across the CRCL -although these varied in quality as regards likely future commercial value. Nevertheless there were a few spin out companies and there was evidence of increasing industrial partnerships. This will help to promote clinical translation and future impact emerging from the CRCL's cancer research.

Overall, the CRCL is on the right track along its journey to become an effective comprehensive cancer centre in the future -linking excellent cancer biology with clinical translation, while training and mentoring the next generation of basic research leaders and clinician scientists. The panel commends the fact that non-clinical scientists and clinical scientists are working side by side to address some of the fundamental problems in cancer research, and importantly, are aware of opportunities to make a difference to the lives of patients where this is feasible. Moreover, the CRCL staff are actively engaged in teaching and training at all levels. The staff, when met by panel members, seemed collegiate and generally pleased with the organisation, and this is testament to the work of the Director and his senior colleagues in developing the CRCL.

Strengths and opportunities in relation to the context

A real strength is in the outstanding leadership of the CRCL, and especially in the area of the links between the basic science and the clinic. Experienced staff in both basic and clincial research are working side by side to optimise the potential for clinical translation, which is excellent. The co-localisation of laboratory science beside, or near, the two treatment hospitals is ideal, and provides superb opportunities. The LYRIC structure is a great asset if it continues to work well for the researchers in Lyon. The 'buy in' at the top of all the organisations involved was rather impressive and provides an outstanding opportunity for integration and success.

A further strength is in the experience and expertise in the biology and clinical treatment of a variety of cancer types and related cancer processes. This includes good preclinical models in many cases.

The organisation within CRCL is excellent, including an excellent management team and three complementary themed departments, together with good administration support and forums for researchers from all staff categories to have input. Communication is excellent. See recommendation 1 below.

There is an excellent cohort of new PIs via external recruitments (mainy from joint ATIP-AVENIR INSERM-CNRS programmes), which makes for a dynamic research environment and staff 'refreshment'; new blood remains vital to all research organisation and this bodes well for the future of CRCL.

The SAB is a real strength and consists of well-respected cancer researchers with abundant experience and good opinions. It may need to be expanded to ensure this as the SAB members are very busy people. See recommendation 2 below.

The first CRCL symposium was a very good start to increasing visibility on the international stage. See recommendation 3 below.

State-of-the-art facilities (eg. animal facilities, genomics, associated bioinformatics, flow cytometry and cell sorting, drug screening, etc.) have grown very rapidly, and provide excellent opportunities for top level science. These needs to be developed further, and made cost-effective and sustainable, particularly animal services and other facilities which need carefully managed. See recommendation 4 below.

Finally, the development of a drug discovery programme is bold, but it is a worthy ambition. However, the goal of taking drugs all the way to the clinic may be over-ambitious for an academic unit. See recommendation 5 below.

Weaknesses and threats related to the context

In the same vein, and as mentioned above, there needs to be turnover amongst teams to refresh, given that space is likely to be limiting either now or in the future, so as to keep recruiting and refreshing -although the panel appreciates this is complex to achieve and challenging, and is tied up with French employment law. See recommendation 6 below.

The panel felt strongly that whilst much of the research was truly outstanding or excellent (at the senior team leader level and some new recruits), there was also some groups who were not performing at the same very high standards. This will be evident from the report on individual teams. It was noted that during the review presentations some of the less strong groups changed the projects from those that were described in the paperwork, which suggested to the panel there may have been a lack of clear research vision and focus in some of these teams. See recommendation 6 below.

There were limited funds to attract post docs -often the life blood of the groups -and PhD students. See recommendation 7 below.

As mentioned above, the international profile of the CRCL is not yet optimised, and should be developed further through multiple mechanisms. The international reputation and visibility of the CRCL teams should be a priority. See recommendation 8 below.

As regards the development of facilities -the panel would caution against too rapid an expansion and ensure that good decisions are made with respect to sustainability plans via internal (or occasional external) facility reviews. With regard to animal useage and the undertaking of expensive projects, it is important that researchers are not tempted to do experiments "because they can", but rather they need to be able to justify the expense on the grounds of scientific value and priority. See recommendation 9 below.

The lack of a few high-end capabilities, such as high-resolution or cellular imaging, and single cell analysis, may be a little constraining for some groups, but the panel is confident this will be put right in due course. All facilities cannot be made perfect at once, and the CRCL is doing well with setting up facilities.

Finally, as mentioned above the development of a drug discovery programme a worthy ambition for CRCL. However, go/no go decision processes need to be very carefully monitored and tightly controlled if resources are not to be wasted. See recommendation 5 below.

Recommendations

The panel recommends (with great enthusiasm) that the director and deputy directors continue on their current path of building towards an effective comprehensive cancer centre in Lyon. The facilities, opportunities and environment are excellent, especially for translational cancer research. The panel is confident the structures and organisation are now in place for the science and impact to go to the next level, and commends the Directorate for their hard work and vision in developing CRCL to this point. In the long term, the panel believes that Lyon will have a cancer centre -linking research and treatment with training and career opportunities -which will be recognised as one of the best in France and internationally. Some specific recommendations are suggested below:

In regard of the points made above two sections:

1. It is important that the good communication existing between management and staff is maintained, and perhaps increased, to ensure that all staff remain engaged and content.

2. The SAB is a real strength, comprising of respected scientists; the panel urges the Director to ensure that the SAB remains fully engaged in key decisions and appointments. It may need to be expanded to ensure this as the SAB members are very busy people. The panel notes from experience of its members, that occasionally SABs can disengage with time.

3. The development of further symposia, interactions, collaborations, educational programmes and dissemination of findings at international meetings is to be encouraged -helping to further build local team spirit, and national and international profile of CRCL researchers and overall CRCL attractiveness to PhD students, post-docs and new PIs.

4. State-of-the-art facilities (eg. animal facilities, genomics, associated bioinformatics, flow cytometry and cell sorting, drug screening; etc.) have grown very rapidly in CRCL, and provide excellent opportunities for top level science. These needs to be developed further, and made cost-effective and sustainable, particularly animal services and facilities which need carefully managed.

5. The drug discovery activities needs to be properly resourced and processes put in place to make go/no go decisions on projects to be pursued and prioritised. With careful development and prioritization, it could lead to valuable output; however, the panel caution that the notion of taking internally CRCL discovered chemical agents into the clinic is perhaps over-ambitious.

6. There is an excellent cohort of new PIs via external recruitments (mainy from joint ATIP-AVENIR INSERM-CNRS programmes), which made for a dynamic research environment and staff 'refreshment'; new blood remains vital to all research organisation and this bodes well for the future of CRCL. Further recruitment, and perhaps some 'team turnover', is recommended if it is possible. It is vital that similar quality standards for internal appointments match those for external appointments.

7. The panel urge that all possible strategies are considered to promote funding of increased post-doc and student numbers. 8. More EU, ERC, H2020, etc. funding applications should be encouraged pro-actively. In particular, there are some team leaders who would be appropriate for ERC applications at the various stages. 9. Regarding animal facilities in particular, Interpretation and guidance on the planning of experiments, and the handling of data acquired from these experiments, are key, and one concern from the panel was that there may not be enough support or oversight in these areas. The CRCL may wish to consider a focussed oversight committee that would internally review expensive animal experiment proposals to ensure maximum value.

  Scientific delegate representing the HCERES: Mr Jean ROSENBAUM Representatives of the unit's supervising institutions and bodies: Mr Alain EYCHENE, CNRS Mr François-Noël GILLY, Université Claude Bernard Lyon 1 Ms Marie-Josèphe LEROY-ZAHMIA, INSERM Ms Françoise MONEGER (representative of Doctoral School BMIC n°340) Ms Marina ROUSSEAU-TSANGARIS, Centre Léon Bérard 1  Introduction History and geographical location of the unit The Cancer Research Centre of Lyon (CRCL, UMR INSERM 1052 CNRS 5286 -Centre Léon Bérard, director Pr Alain PUISIEUX) was initiated in January 2011 in order to create a centre of excellence in tumour biology and participate in education and training in oncology in Lyon. The CRCL relies on strong links established with clinical departments from the Léon Bérard Centre and the Hospices Civils de Lyon, fostering translational research aiming to improve the lives of patients.

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 (staff with half-time research activities)

	nomenclature SVE1_LS3 Biologie cellulaire, biologie du développement animal SVE1_LS6 Immunologie, microbiologie, virologie, parasitologie SVE1_LS1 Biologie moléculaire et structurale, biochimie N2: Permanent researchers from Institutions and similar positions SVE1_LS4 Physiologie, physiopathologie, 53 55 N3: Other permanent staff (without research duties) +	62 65

CRCL staff members affiliated to common services and technological platforms

		61	73
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.) including PH with part-time research activities	21	33
	N5: Other researchers (Emeritus Research Director, Postdoctoral students, visitors, etc.)	38	38
	N6: Other contractual staff (without research duties)

including CRCL staff members affiliated to common services and technological platforms 27 33 TOTAL N1 to N6 255 304 Unit workforce Number as at 30/06/2014 Number as at 01/01/2016

	Doctoral students	65
	Theses defended (in the 2009-2014 period)	112
	Postdoctoral students having spent at least 12 months in the unit (in the 2009-2014 period)	52
	Number of Research Supervisor Qualifications (HDR) taken (in the 2009-2014 period)	11
	Qualified research supervisors (with an HDR) or similar positions	77	90


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:

 Introduction

This unit proposes a complete reorganisation for the next contract and will be renamed "Viral infections and comparative pathology". From three teams, the unit will be remodeled in one team concerned by four scientific projects. Therefore this report will take this essential modification into account and the assessment will be made on four teams: the three first teams (Teams 1-3) refer to the current unit for the past contract; the fourth (Team 4) assessed team represents the new organisation of the unit in one single team.

History and geographical location of the unit

The UMR 754 "Retrovirus and Comparative Pathology" is located on the Gerland Campus of the University Claude Bernard Lyon 1 (UCBL1). The unit has been created in 2003; it has been renewed in 2007 then in 2011. The unit belongs to the UCBL1 and the Institut National de la Recherche Agronomique (INRA, Animal Health Division). The unit is associated to the École Pratique des Hautes Études (EPHE), VetAgroSup and Hospices Civils de Lyon (HCL).

Management team

Director: Mr Jean-François MORNEX Deputy Director: Mr Christophe TERZIAN Project Leader: Mr Christophe TERZIAN Pr Jean-François MORNEX is the director of the unit since its creation and Pr Christophe TERZIAN the deputy director since January 2013 and is going to take the lead of the unit for the next contract. 2  Overall assessment of the unit

HCERES nomenclature

SVE1-LS3, SVE1-LS6 and SVE1-LS7

Unit workforce

Unit workforce

Global assessment of the unit

The UMR Retrovirus and Comparative Pathology (RPC) is a medium-sized unit of 22 permanent staff, organized in 3 research teams during the evaluation period. The unit focuses on pathogens and host-pathogen interactions and includes the "One health" concept in its strategy. Historically, the unit is dedicated to retrovirology, and has a recognized expertise in the field of animal retroviruses JSRV (Jaagsiekte sheep retrovirus) and EIAV (Equine infectious anemia virus). Globally, the unit is recognized in the field of pulmonary tumor diseases in animals and humans. Since its creation in 2003, the missions of the unit have evolved from pathogenesis of animal retrovirus infections (in sheep and horses) to basic and applied research on retroviruses, on arboviruses (namely bluetongue virus) and vectorology based on adenoviruses. A number of striking results have been obtained in the different topics addressed. For instance, the unit demonstrated that Wolbachia infection of flies reduces the vertical transmission of the endogenous retrovirus Gypsy, or evidenced the presence of ovine bronchioloalveolar progenitors, thus providing new tools to study lung regeneration. In parallel, diagnostic tools have been developed and proofs of concept have been provided regarding the use of viral vectors or other therapeutic tools (leading to 4 patents). The unit is well involved in teaching and training by research. In addition, the unit is strongly integrated in the SFR BioScience Gerland Lyon 1. The overall assessment of the unit is excellent.

Strengths and opportunities in relation to the context

An effort is being made to reorganize the unit and to make it attractive when facing the current scientific challenges (grant applications, biotechnologies, international competition). The unit has technical skills regarding 3D cell culture, what allows analyses on the cell response to viral infections. The unit has developed a Bio-safety level 3 (BSL3) insect facility allowing research on arboviruses.

The unit has a strategic position with an animal health specialty in Rhône-Alpes. The unit demonstrates a good insertion in Lyon university life (strong involvement in teaching, medical care, SFR functioning and management, opportunity with the Institut de Recherches Technologiques (IRT) Bioaster.

The doctorate students are happy to work in the unit because of a good follow-up of their work by the tutors, of their involvement in the writing of scientific articles and an enough granting of their research.

The unit is well supported by its management bodies: the project is on line with the strategy of INRA, close to Anses (Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail) and complementary to Lyon "International Research Center for Infectious Diseases" (CIRI, established in 2013, has over 20 multidisciplinary teams addressing the control of infectious diseases) in terms of animal health; the "animal health" component is of upmost importance for the university UCBL; for EPHE, the unit, despite a modest size, is an important partner in Lyon and its only location for the subject virology-infectiology.

Weaknesses and threats related to the context

A rather diversified number of research topics considering the size of the unit.

Moderate funding in respect to the four research projects proposed in the new contract.

An insufficient level of collaboration with VetAgroSup is noticed, despite the "animal health" and the "One health" dimension of the unit.

The scientific animation is not developed enough and there is a need for enhanced exchanges within the unit.

Recommendations

The "One health" dimension of the unit must and will be continued and should be strengthened. The retrovirus research remains the foundations of the unit and should be maintained; the interplay between animal and human health should be reinforced (i.e. the increased incidence of lepidic tumours in lung cancer patients in contact with goats) together with the collaboration between scientists and clinicians.

Taking into account the size of the unit and the level of granting, it is recommended to lower the diversity of the scientific subjects and the unit should prioritize the subjects. The effort of remodelling the unit should be pointed out as a proof of its dynamism although the number of topics proposed in the new contract is still high.

Concerning the scientific life, the scientific animation (journal club, team meeting,…), the attraction of foreign doctoral students and post-docs should be improved.

  Mr Olivier SANCHEZ, Université Paris Descartes (representative of the CNU) Ms Anne-Nathalie VOLKOFF, INRA, Montpellier Scientific delegate representing the HCERES: Ms Sophie EZINE Representatives of the unit's supervising institutions and bodies: Ms Sylvie DEMIGNOT, EPHE Mr Germain GILLET, University Claude Bernard Lyon 1 Mr Thierry PINEAU, INRA Ms Sylvie REVERCHON (director of the Doctoral School N°341 -E2M2 " Évolution Écosystèmes Microbiologie Modélisation ")

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

	and similar positions	6 (4)	5 (2.8)
	N2: Permanent researchers from Institutions and similar positions	5 (4.8)	6 (5.8)
	N3: Other permanent staff (without research duties)	13 (11.8)	12 (10.8)
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)	2 (1.5)
	N5: Other researchers
	(Emeritus Research Director, Postdoctoral students, visitors, etc.)
	N6: Other contractual staff (without research duties)	1 (1)
	TOTAL N1 to N6	27 (23,1)	23 (19,4)

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

	Doctoral students	7
	defended Theses	10
	Postdoctoral students having spent at least 12 months in the unit
	Number of Research Supervisor Qualifications (HDR) taken	3
	Qualified research supervisors (with an HDR) or similar positions	13	11


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:

Centre for Cognitive Neuroscience

Management team

Seven independent teams compose the Centre for Cognitive Neuroscience. The CNC is now under the directorship of Mr Jean-René DUHAMEL and will be directed by Ms Angela SIRIGU for the next term. 2  Overall assessment of the unit

HCERES nomenclature

Global assessment of the unit

The Centre for Cognitive Neuroscience has the competitive strength in neuroscience in the international domain essential for the understanding of the behavioural and neural basis of complex behaviours and the treatment of neurological disorders. The common interest of the five teams converge upon the study of the behavioural dimension and the neural basis of spatial perception, motor control, attention, decision making, reward structure and social cognition.

Strengths and opportunities in relation to the context

It was apparent to the experts committee that the unit is open to exploring new themes for inter-and transdisciplinary research and investigating new areas in a creative fashion. Examples of this are social cognition in human and non-human species, rewards and neuroeconomics, schizophrenia and quite a few others. Mutiple methods were in use and new ones are being devised such as linking PET and fMRI measurements, monkey modelling of Parkinson Desease, and the notion of two different reward systems. Other equally groundbreaking developments are under consideration such as remote wireless recording of some brain structures, for example the amygdalae. The experts committee observed the deliberate objective to combine non-human and human approaches when feasible, often resulting in integrated methods. Development is underway this year to integrate fMRI and PET, a process that will have huge payoff in interaction and efficiencies and likely present unique possibilities.

The breadth of themes in the work is considered appropriate for the size of the teams and the number of researchers.

Weaknesses and threats related to the context.

No major weaknesses of the governance and the staff were noted. The experts committee did observe that the training period for technical people was long and feel that more engineers are called for. There also appeared to be a lack of long-term perspective for technical support personnel. The housing for monkeys seemed rather limited even at the current number of scientists and especially if the number of projects increases in the future.

There is a possible threat that the new fMRI facility may not be funded for non-human primate research although the University representative informed the experts committee that this funding was now assured. The experts committee feels that the funding could be extended by selective collaborations inside EU grants.

The panel believes that more could be done to integrate the clinical staff that have full-time positions. They may have different priorities but their contributions could facilitate the work of the researchers.

Recommendations

Based on its reading of the reports and its site visit the experts committee is in a position to formulate a few recommendations. One is to facilitate more organized inter-team consultations between the members of the different teams, including at the level of the technical support staff. For example, regular contacts that include the technical staff might allow not only exchange of methodological insights but also the joint development of new solutions and developments. It may also be important to promote increased awareness of novel solutions to the methodological and technological challenges, some of which are to be expected and others sometimes unexpected.

A second recommendation is to continue to provide more integration between the clinical and the research staffs. Ideally there should be continuous two-way traffic between the two. This would allow the group to maximize the unique signature of this unit where both theoretical and clinical approaches are uniquely represented.

Finally, the experts committee would like to encourage more informal scientific meetings amongst the different teams to stimulate interactions. This interaction might reveal novel and rich solutions to the different questions addressed by each of the teams.

  , Université de Tours Mr Pascal MAMMASSIAN, École Normale Supérieure, Paris (representative of the CoNRS) Mr Pierrick POISBEAU, Université de Strasbourg (representative of the CNU) Ms Eleni SAVAKI, University of Crete, Grece Mr Wolfram SCHUTZ, Cambridge University, UK Scientific delegate representing the HCERES: Mr Jacques NOEL, Scientific Delegate Representatives of the unit's supervising institutions and bodies: Mr Denis FOUQUE, University Claude Bernard Lyon 1 Mr Remi GERVAIS (director of Doctoral School n° 476) Mr Jean Louis VERCHER, CNRS 1  Introduction History and geographical location of the unit Created in 2007 as an "Unite Mixte de Recherche", the Cognitive Neuroscience Centre (CNC) is located in the University campus in Bron near Lyon within the "Institut des Sciences Cognitives" (ISC). It is dedicated to research on the neural mechanisms of cognition and its disorders and is situated in close vicinity to several hopsitals (the Neurology Hospital, Hôpital Edouard Herriot, Vinatier psychiatric Hospital). For the next contract the lab will claim the label "Institut de Science Cognitive Marc Jeannerod".

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)


François-Loïc Mr

Cosset

Jean-Marc Mr

Reichhart

Ms Sophie Caillat-Zucman

Cecil Mr

Nice Czerkinsky

Dominique Mr

Garcin

Yves Mr

Gaudin

Roger Mr

Hewson

Mr Sylvain

Philippe Mr

Pierre

Ms Ana Sousa

Mr Joost

Van Meerwijk

As for now, 18 teams of the CIRI have been relocated on the Lyon Gerland Campus, however not yet in the same building, while one team is still located at the La Doua Campus, another at Campus Laennec and a third partly at Campus Lyon-Sud.

Management team

The CIRI was created in 2013 for a two-year period with Mr François-Loïc COSSET as head. For the new five-year contract, Mr François-Loïc COSSET will be the director, assisted by Mr François VANDENESCH as deputy director, an executive Board (the director, the deputy director, the general administrator who assists the director in administrative duties, and four delegate directors, Mr Andrea CIMARELLI, Mr Mathias FAURE, Mr Renaud MAHIEUX, and Ms Jacqueline MARVEL, elected from the team leaders) and a board of team leaders (23 team leaders total in the new geometry of the CIRI) for the strategic decisions. 2  Overall assessment of the unit

HCERES nomenclature

SVE1_LS6 Immunology, microbiology, virology, parasitology

Unit workforce

Unit workforce

Global assessment of the unit

The International Centre for Research on Infectious diseases (Centre International de Recherche en Infectiologie) or CIRI, created in 2013 under the supervision of INSERM, CNRS, ENS Lyon, UCBL, the Pasteur Institute and the Hospices Civils de Lyon, gathers 20 teams from the Lyon area working on infectious diseases. The committee felt that the grouping of these teams in a single unit was a very pertinent initiative, giving rise to a highly productive centre where the respective competences of the different founding teams are fully integrated into a cross-fertilized research on infectious diseases. By many aspects, the CIRI is a high-achieving centre, fully integrated in the industrial and clinical landscape of the Lyon area, which publishes in high quality journals and has secured impressive founding from private, national or international agencies (e.g. four ERCs). A guarantee for the future and the positive development of the CIRI is that the founding teams have been able to attract and/or develop quite an impressive number of high profile junior researchers, three of which have developed their own group and are proposed to integrate the CIRI for the next period.

Strengths and opportunities in relation to the context

The publication record of the founding teams has been excellent and, since its creation, the collaborative intra-CIRI publications have improved in terms of quality and impact.

The close and very effective collaboration between the immunology and microbiology or virology teams, which was central in the creation of the CIRI, is an added value.

Given the attractiveness of the research environment, the centre has been able to attract and/or develop very promising young researchers as assessed by the fact that their projects have been supported by competitive funding sources (such as two ERC "starting grants"). These young PI's have integrated or will now integrate the CIRI as new teams for the next period.

The rich environment of the Lyon region in terms of common facilities, public (SFR Biosciences, the BioSafety Level 4 (BSL4) facility, which is unique in France) or private (BioAster Technology Research Institute (TRI)), guarantees the development of the proposed research and projects.

The close interaction with the clinical centres in the hospitals is a major strength in terms of development of clinical translational programs. The committee has noticed a well-balanced development of the research between fundamental and translational.

The strong interaction with the Lyon academic life (Master-programs and PhD schools), providing a reservoir of young students and researchers to the CIRI. Almost all the teams have secured an impressive amount of funds for the next period, again guarantee for the development of the proposed projects.

Weaknesses and threats related to the context

The main weakness that the committee has noticed is the still dispersed localisation of some of the CIRI teams, which is a threat to the scientific life of the centre.

Whereas research of some of the CIRI-teams depends heavily on the BSL4 laboratory, the local access to this facility appears difficult.

The committee has also seen a weakness in the possible future inequality of funding between different teams, which are competing for the same, more and more limited, resources.

Recommendations

The committee recommends that the direction of the CIRI put major efforts in securing as quickly as possible the funds and the space in order to relocate as many teams as possible on the same site in Lyon Gerland.

The access to the BSL4 laboratory, which is essential for the research of the CIRI, should be optimised and secured and a priority access should even be negotiated if possible.

Since its creation, the quality of the work conducted in the CIRI continues to grow in terms of basic and translational research, academic reputation and teaching. The unit organisation and life is excellent as judged by the satisfaction of the staff and students to work at CIRI and the final recommendation of the committee is to keep going and growing.

  Representatives of the unit's supervising institutions and bodies: Mr Fabrice CORDEY (representative of the Doctoral school 341) Mr Hubert ENDTZ, Fondation Mérieux Mr Germain GILLET, University Claude Bernard Lyon 1 Mr Frank LAFFONT, CNRS Ms Monique LAFON, Institut Pasteur Ms Françoise MONEGER (representative of the Doctoral school 340) Ms Stéphanie POMMIER, INSERM Mr Yanick RICARD, ENS Lyon Mr François TEILLARD, Lyon Hospitals (HCL) 1  Introduction History and geographical location of the unit The International Center for Research on Infectious diseases (Centre International de Recherche en Infectiologie) or CIRI was created in 2013, with the goal of regrouping the teams working on infectious diseases from the Lyon area. The fairies that leaned over the crib were INSERM, CNRS, ENS Lyon and University Claude Bernard Lyon 1 (UCBL) together with the Pasteur Institute, and the Hospices Civils de Lyon. The CIRI, which is a joint research unit (U1111 INSERM-UMR CNRS 5308-ENS Lyon-UCBL) merged from two core-founding bodies: the former Human Virology (U758 INSERM-ENS Lyon, director Mr François-Loïc COSSET) and Immunity, Infection, Vaccination (I2V; U851 INSERM-UCBL, director Ms Jacqueline MARVEL) units. Three other teams, the "Legionella pathogenesis" (from CNRS), the "Biology of Emerging viral Infections" (UBIVE from Pasteur Institute) and the "Emerging Pathogen Laboratory (Fondation Mérieux) joined this core of 17 teams and the CIRI represents now 20 teams and more than 300 researchers, technicians and graduate students.

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

	and similar positions	35	45
	N2: Permanent researchers from Institutions and similar positions	39	37
	N3: Other permanent staff (without research duties)	65	75
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)	9	6
	N5: Other researchers (Emeritus Research Director, Postdoctoral students, visitors, etc.)	24	18
	N6: Other contractual staff (without research duties)	34	21
	TOTAL N1 to N6	206	202

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

	Doctoral students	55
	Theses defended	75
	Postdoctoral students having spent at least 12 months in the unit	17*
	Number of Research Supervisor Qualifications (HDR) taken	7
	Qualified research supervisors (with an HDR) or similar positions	42	47
	* As defined by INSERM up to 3 years after the PhD. Three years after their PhD, they are categorized as
	"researcher on non permanent position"


 Introduction History and geographical location of the unit

The Stem Cell and Brain Research Institute (SBRI) is located in Lyon and was created in 2007 by Mr Henry KENNEDY and in 2011, renewed under the directorship of Ms Colette DEHAY, with Mr Henry KENNEDY as deputy director. SBRI is affiliated to Inserm and University de Lyon 1 Claude Bernard with strong links to INRA and CNRS. SBRI research is multidisciplinary with interests ranging from stem cells biology, developmental neurobiology, integrative and cognitive neuroscience, chronobiology disorders and robotics.

Management team

Since 2011 the SBRI is under the directorship of Ms Colette DEHAY, with Mr Henry KENNEDY as deputy director.

HCERES nomenclature SVE, LS5 Neurobiologie, LS3 Biologie cellulaire, biologie du développement animal. 2  Overall assessment of the unit

Unit workforce

Global assessment of the unit

The SBRI unit is a unique research institution in that it unites under the same roof seven, and in the future 9 self-sustaining groups that are active in different fields of research ranging from stem cell research all the way up to cognitive psychology and robotics. The common denominator is the shared interest in the development, structure and function of the brain. This assures strong cohesion among the groups, reflected by an impressive number of shared publications and joint utilization of a broad spectrum of methodological and disciplinary competences. This added value of interdisciplinarity is further enhanced by the availability of a rich and well managed technical infrastructure that provides state of the art equipment and competent service to all groups of the institute. In addition to its interdisciplinary nature the institute is distinguished by several other remarkable features:

1) the focus on comparative research in rodents and non human primates, the latter having become a deplorable rarity in Europe;

2) the efforts of all research groups to invest in translational research with respect to both clinical and industrial applications;

3) the strong and very productive engagement in both national and international research networks, which assures access to complementary know how and infrastructure not available in the institute; 4) the remarkable success in attracting third party funding with the surprising effect that 87% of the recurring budged is secured by non-institutional funding.

Strengths and opportunities in relation to the context

Quality of science: the major strength of the height teams assembled in the SBRI is the outstanding quality of their scientific leaders, some of which are among the world leaders in their fields. For this very reason the research topics pursued by the various groups are at the forefront of the world wide attempts to understand the brain in health and disease and the quality of the pursued research is at the highest international level. Due to the strong and well managed infrastructure, the applied methods are cutting edge and comply with world standards. Accordingly the quality of the publications of the various groups is excellent as documented by the large number of papers that got accepted in high ranking journals and the impressive amount of peer reviewed funding from external sources. This very successful recruitment of extramural funding by both local and international agencies also testifies that not only the track records of the applicants but also their visions for future projects are judged as highly competitive. These markers of quality are complemented by the high international visibility of the institute and its scientists. These are invited to participate in prestigious conferences, to give talks at universities with high standing and to publish reviews on their work in high impact journals with peer review. While all research lines pursued in the institute are addressing the most challenging questions in contemporary brain research, the combination under the same roof of stem cell research with investigations in non-human primates is extremely rare if not unique. It has the great potential to lay the grounds for stem cell therapy in human subjects and the development of transgenic monkeys. Both are among the most challenging but also promising endeavors of contemporary brain research. Remarkable is also the complementation of biological research with cutting edge computational modeling and robotics. These fields have not only become essential for progress in the neurosciences but have considerable translational potential for the design of intelligent artifacts. The review committee unanimously subscribes to this appreciation of the science performed by the scientists of SBRI.

Institutional dynamics: there is a high turnover of scientists at the level of students and postdocs. Many PhD students move after their exam to excellent institutes in other countries and are replaced by recruitment of highly qualified postdocs, mainly from Europe. Often these have been formed in the institute and now attempt to return after their postdoc and apply for positions at Inserm, CNRS and INRA. Others join as postdocs on time limited contracts. The continuity is assured in addition to the PIs by 22 researchers with permanent contracts, three of which possess HDRs, the qualification to supervise PhD students. The high dynamics of the institute is also reflected in the recent recruitment of two further teams which are complementing the already strong focus in stem cell research. Thus, the institute is engaged in a very valuable and constant renewal process. The concomitant expansion of methodological expertise and research activities is coped with by recent important investments in common service structures and additional labs. Due to national regulations there is, however, a continuous drain of expertise caused by highly trained PhD students who have to leave the institute 6 months after their exam. Usually publications based on the thesis work are not accomplished at that time and the students have little chance to participate in training of their successors.

Governance: a particularly noteworthy and highly appreciated feature of this institute is its lean and cooperative management structure (a double headed directorate, a pilot committee consisting of the directorate and the time leaders and the "conseil de laboratoire"). This rather horizontal structure allows for short paths, fast responses and a high degree of flexibility. Although the various units are independent with regard to their budget and scientific goals and the institute comprises numerous and heterogeneous personnel (students, postdocs, tenured senior scientists, technicians, animal keepers and engineers), all parties are well represented in the respective governance bodies and are invited to participate in the deliberations on matters of concern on a regular schedule. An appreciated aspect of this cooperative structure is the shared use of high-end technical infrastructure. This allows pooling of resources, recruitment of highly competent service personnel and implementation of expensive high performing instrumentation. Well adapted to the "democratic" governance structure of the SBRI is the fact that it is headed by a director and a co director, two personalities that ideally complement one another with respect to seniority and scientific competences. Their joint expertise covers a large part of the institute´s research agenda.

Teaching: there is no formal obligation for the institute's scientific staff to engage in teaching. The initiative to engage in teaching is left essentially to the individual scientists. Some of them take this opportunity, offer lectures and courses and use these contacts to recruit master and PhD students for their teams. The institute is also engaged in two graduate schools in cooperation with the University of Lyon, from which a small number of PhD students is recruited. The number of successfully supervised master and PhD theses is appropriate given the number of scientists possessing HDRs.

Outreach: the staff of the institute is to be felicitated for the remarkably intense efforts to communicate the goals and results of their research to the public at large in public talks and the media, to engage in discussions on animal rights as well as on the general ethical aspects and societal consequences of their research.

Translation: the tight connections of certain groups to clinical departments in Lyon and Grenoble and the cooperation with industrial partners have the highly appreciated consequence that each of the groups devotes some of its resources to translational research. These initiatives are remarkably successful as testified by patents and formal cooperation treaties.

Economic efficiency: the relation between budget and productivity is excellent and matches that of other renowned research institutions, even though the institutional funding is considerably lower than in comparable institutes abroad. This is remarkable as it indicates that the scientists at the institute maintain high output despite the fact that they must invest much of their time to writing grants and applying for extramural funding. Just as the time limits for PhD students lead to a continuous drain of expertise, the legal limits for renewal of contracts of the technical staff make it very difficult to cultivate and preserve the know how needed for the management of the technically very challenging infrastructure. The institute is to be felicitated to keep up with world standards despite these severe constraints.

Cooperation: to maintain the high degree of interdisciplinarity and to assure access to methods not available in the institute, the teams have entered into cooperation with other institutions both in Lyon and abroad for deep sequencing, bioinformatics, flow cytometry, MRI imaging in humans and non human primates, computational modeling, development of transgenic monkeys. These initiatives have led to the foundation of remarkably diverse and high quality multi-user platforms in the Lyon region. Moreover, all groups participate in various constellations in both local clusters of excellence (e.g. LabEx CORTEX) and international research consortia. These cooperations permit pursuit of challenging projects that would not be realizable by only relying on the institute´s infrastructure and greatly enrich through regular meetings and seminars the curricula of students and staff and consolidate the embedding of the institute in the scientific community of Lyon.

Weaknesses and threats related to the context

Identified weaknesses and potential threats are mainly due to external factors that can be influenced only little by directorate and the staff. One problem is the low level of intramural funding which makes it difficult to plan long-term investments for future developments. At present, a large part of the shared services is financed by the overheads of extramural funds acquired by the PIs. This may preclude acquisition of expensive equipment that cannot be justified by individual grants. Intramural funding is used mainly for the maintenance of the status quo, the modest extension of lab space and the salaries of permanent non scientific staff. The admirably lean infrastructure at the administrative level is problematic as the extensive funding through third parties and the need for local networking with shared infrastructures causes heavy administrative load that cannot be coped with on the long run by the present secretarial staff. Already now, a substantial part of administrative duties are taken on by the scientists. Following the recruitment of two new teams, the institute is now also at the limit of possible expansion and further implementation of new lines of research or extension of projects will require investment in the building. Another problem is the limited duration of contracts with technicians and engineers working in the service departments (Sauvadet Law). Such positions are difficult to finance through grants and if intramural funds permit only temporary employment, it is virtually impossible to obtain and maintain a high level of competence and continuity in these domains. As high tech support becomes increasingly important for cutting edge science this jeopardizes the quality of the institute´s research. A further weakness imposed by the system is the limitation of contract duration for postdocs. It leads to the drain of competences mentioned above and often makes it impossible for the best of the young researchers to obtain grants (ERC, Marie Curie, etc.) for the consolidation of their own research career. These grants are given for periods of usually five years and are meant to pave the way into an independent research career. In other European countries these grants are often the basis for later promotion to tenure positions. Postdocs at the institute cannot stay for the duration of such grants. Their only option for staying at the institute is recruitment by Inserm, CNRS, INRA or UCBL, which greatly restricts early independence and mobility and deprives the institute of the most competitive young researchers. Finally there is the danger that the institute will lose its outstanding profile in the domains of informatics, simulation and robotics. These disciplines become increasingly important for biology and particularly for brain research. The reason is that biological systems, and above all the complex brains of mammals, exhibit exceedingly complex, non linear dynamics which require for analysis sophisticated mathematical algorithms and massive computing. At the moment the institute lacks high level engineers in this field, again a consequence of the imposed employment policy and this lack cannot be compensated by outsourcing.

A minor but noteworthy threat is a certain difficulty in the recruitment of students (master and PhD) which is reflected in the number of supervised theses. Here intensification of teaching activities, organisation of schools and an increase of positions made available by the two graduate schools might be helpful. In this context it is worth mentioning that non French speaking scientists have difficulties to profit from courses required to obtain licenses, e.g. for animal experimentation, because most of these courses are offered only in French.

Recommendations

The major threats for the institute's future (legal constraints for the employment of scientists and technicians, low recurrent funding, space limitations) cannot be countered by the institute. To somewhat mitigate the recruitment problem of students, engagement in teaching and qualification for HDRs should be encouraged. Efforts need to be made to recruit more secretarial help, to maintain the high level of expertise in the domain of high tech infrastructure and to recruit additional engineering competence for informatics and supercomputing. It might also be considered to change the affiliation of the institute with the university and to switch from the life sciences to the sciences as this might alleviate some of the recruitment problems.


It was planned that a new building of 5600 m 2 will be constructed on the East-Lyon Hospital site and that the teams that are currently at remote places in Lyon would be hosted in this building to allow most of the CRNL teams being located on the same campus (Neurocampus). The opening of the building was originally scheduled for 2013 but completion of this estates project has been delayed and only a first part of the building (3700 m 2 ) is foreseen to be available in 2017. Funding for the second phase with further 2000 m 2 hasn't been secured yet. As a consequence of this, the various teams and platforms are still scattered on different sites across the City.

The CRNL staff is currently made of 374 persons, 135 of them permanent researchers (84 FTE), 67 technical staff and 172 students (Masters and PhD). There are 9 CRNL-internal technical platforms and an independent multimodal neuroimaging facility for animals and humans that the CRNL uses on a fees-for-service basis.

Management team

The CRNL is composed of an Executive Team (director and deputy-director), the Executive Bureau (Executive team & 4 CRNL members), the Board of Team leaders and a Center Council consisting of 15 CRNL members who meet 2-3 times a year). Director and deputy-director are also both leaders of a CRNL team.

A General Assembly is organized once a year.

A Scientific Advisory Board has been instated, consisting of ten international experts. The Board made a site visit in 2014 and provided advice on existing projects and the creation of new teams.

The CRNL has established nine research platforms that are operated by CRNL members and are accessible for all teams. The platforms provide technical infrastructure and expertise for neurochemical quantification, optogenetics, microscopy and electrophysiology for animal experimentation, as well as facilities for immersive reality, EEG, neurostimulation (TMS and tDCS), 3D assessment of motor behavior and intracranial recordings in humans. There is also a CRNL-internal IT support platform.

The CRNL makes extensive use on a fees-for-service basis of the Life Imaging Center (CERMEP) located on the East-Lyon Hospital Campus. Some of the facilities are coordinated or headed by senior members of CRNL from the BIORAN and DYCOG teams. The imaging Center includes an animal imaging platform with micro-PET, 7T MRI and human imaging platforms including PET with a cyclotron facility, 3T MRI, MEG/EEG, and since summer 2014 an MRI-PET system.

The CRNL has particularly strong connections to clinical groups and this facilitates access to clinical resources and patient cohorts for clinical research. A new Epilepsy Institute (IDEE) with a 1500 m 2 purpose-built facility is predicted to be available in late 2015. IDEE will be coordinated by the TIGER team, while the research space (500 m 2 ) will belong to the Neurocampus and will be managed by the CRNL. 2  Overall assessment of the interdisciplinary unit

HCERES nomenclature

Global assessment of the unit

The Center strongly promotes translational research with a multi-scale and multi-level approach that spans from molecular/cellular research in animal models to the study of large-scale brain networks and of human behavior. The strong integration with clinical groups allows direct translation of research findings to diagnostic, therapeutic and prognostic applications in clinical settings and access to patient recruitment to research studies aimed at understanding pathophysiological mechanisms of neurological diseases. The Center is organized around 3 thematic axes with several teams contributing to more than one theme. The 3 axes are embedded in 2 main research directions: from gene to behavior, and from bench to patients. Axis 1 (Perception, Attention, Action) investigates mechanisms of olfaction, nociception, auditory processing and sensorimotor integration in humans using a wide range of experimental methods as well as animal models. Axis 2 (Memory, Emotion, Social Cognition) looks at learning, plasticity and social interactions in healthy and clinical populations. Axis 3 (Sleep, Waking, States of consciousness) studies sleep and wakefulness regulation in animal models and in humans. During the first 3 years of the Center two new axes have emerged and ultimately led to the creation of new teams for the proposed second 5 year term: Axis 4 (Genetics and Phenotypic Flexibility) that studies neurodevelopment and neuroprotection and Axis 5 (Blood-Brain Interfaces) that looks at development of the blood-brain interfaces and searches for biomarkers of neurodegenerative diseases.

Strengths and opportunities in relation to the context

One of the main strength of the Center is the close link and the collaboration with clinical units; this is a critical element for a successful translation of the research findings to clinical applications. Likewise, the ease of access to clinical populations and cohorts allows to study brain dysfunctions directly in humans and exploring new therapeutic strategies. Due to this strong historical connection to the clinical environment, the impressive distinctiveness of the Center is the genuine translational research, of which the development of biochemical PET biomarkers for neurodegenerative disease, the improvement of pain diagnosis, the discovery of a cascade of events that precede cardiac failure in SUDEP, or the improved treatment of hemi neglect are just some examples.

A second important strength is the outstanding work of the director of the center. He accomplished the formation of an impressive research center of high national and international recognition despite all political and administrative complications that one has to face to put such a center together. Without his personal dedication and enthusiasm this center would not exist in it's current form.

Overall, Center researchers use a variety of sophisticated methodological approaches and analyses methods in both humans and animal studies. The available platforms and technological resources are of exceptional standard and allow multidisciplinary research at all levels. Most of the teams make significant use of these opportunities and approach their research questions on different scales and with different methodologies. Many teams study their research topic in animal models, in vitro and in vivo, and in humans and try to integrate the findings in a global understanding of brain functions. As a result, research produced by members of the Center is published in journals with a multidisciplinary audience.

With 1150 peer-reviewed articles published in the last 5 years, the Center's production is excellent in terms of quantity. Several publications have been accepted in journals with high international reputation. The citation rate is also generally excellent as seen by the high H-index of some of the team leaders.

Recruitment and training of PhD students is excellent. The neuroscience PhD program is successful and well structured and so is the organization of the Master School.

Weaknesses and threats related to the context

An obvious threat is the continuing dispersion of the Center in different parts of the city despite the planned new location having been forecasted for 2013. The campus will be delayed by more than 4 years and will still be only partly available in 2017. Despite remarkable efforts, this geographic scattering has significantly hindered the collaboration between the different teams. The geographic dispersion also hampered the Center to appear as a real unitary entity.

While the diversity of research themes and approaches is impressive, it also bears potential risks of not having sufficient resources and manpower to be internationally recognized as a Center of excellence in any specific domain. Some teams are small with only very few full-time researchers. The smaller teams may have difficulties in having a global impact and consequently struggle to be seen as attractive to high-quality international researchers. This becomes obvious when looking at the composition of the tenured researchers that are to an overwhelming majority from France.

The Center has been very successful in securing national competitive research grants, particularly with respect to the Labex, PHRC, ANR and Foundation calls. However, the number of international competitive grants is comparatively small, particularly when we look at the number of EU grants.

Concerning publications, the number of published papers that include authors from different teams is still small despite the very obvious overlap of research questions and methodologies. The growing interactions described in the project should help improve this point for the next five-year period.

Recommendations

The site visit and the discussion with the different researchers and representatives led to the following general recommendations:

1. the new buildings for the Neurocampus are absolutely mandatory for the flourishing of the Center. The phase 2 building is crucial not only to bring in the rest of the teams but also and most importantly to be able to develop new research strategies and axes and to attract new researchers to the teams;

  CoNRS) Mr John FOXE, Albert Einstein College of Medicine, New York, USA Ms Anita LUETHI, University Lausanne, Switzerland Mr Pascal MAMASSIAN, École Normale Supérieure, Paris (representative of the CoNRS) Mr Phillippe PEIGNEUX, Université Libre de Bruxelles, Belgium Mr Cyriel PENNARTZ, University of Amsterdam, The Netherlands Mr Mathias PESSIGLIONE, Hôpital Pitié-Salpêtrière, Paris (representative of the CSS INSERM) Mr Michel POHL, Université Paris Descartes, France Mr Jean-Philippe RANJEVA, Aix-Marseille Université (representative of the CNU) Mr Stefano SERI, Birmingham Children's Hospital and Aston University, UK Ms Daniela VIRGINTINO, Bari University, Italy Scientific delegates representing the HCERES: Mr Jacques NOËL Ms Celine SOUCHAY Representatives of the unit's supervising institutions and bodies: Ms Michèle COTTIER, Université Jean Monnet M. Remi GERVAIS (representative of the Doctoral School NsCo -n°476) M. Germain GILLET, UCBL Ms Anne ROCHAT, INSERM M. Jean Louis VERCHER, CNRS 1  Introduction History and geographical location of the unit The CRNL was created in January 2011 with the aim of merging the different research laboratories in the area that already had tight scientific interactions and that shared facilities within the Lyon Neuroscience Federative Institute. The Center was organized in 11 teams coming from Inserm, CNRS, the University Claude Bernard Lyon 1 and the University Jean Monnet Saint-Étienne. These four institutions now form the supervisory authority of the CRNL. The Lyon University Hospitals and the Vinatier Psychiatric Hospital are the clinical partners.


 Introduction

History and geographical location of the unit EMR 3738 was founded in 2003 in Lyon and is a mixed academic unit of Université Claude Bernard de Lyon (UBCL) and Université Jean Monnet St-Étienne. The unit is focused on clinical cancer research and includes three teams with the following specialties:

Team #1: surgery (cytoreductive surgery [CRS] and hyperthermic intraperitoneal chemotherapy [HIPEC]); Team #2: chemotherapy (predictive pharmacology and early clinical trials); Team #3: physical agents (radiotherapy); Team 4 (hadron therapy) was part of EMR 3738 from 2006 to 2014. Since Team 4 leaves the unit at the end of 2014 it is not part of the present research evaluation.

Management team

The head of the unit is Prof. François-Noël GILLY.

Team leaders are Prof. Olivier GLEHEN (Team #1), Prof. Gilles FREYER (Team #2) and Prof. Françoise MORNEX/ Prof. Olivier CHAPET (Team #3). 2  Overall assessment of the unit

HCERES nomenclature

SVE1_LS7 Epidémiologie, santé publique, recherche clinique, technologies biomédicales

Unit workforce

Unit workforce

Global assessment of the unit

There have been a number of practice-changing advances in cancer surgery brought about by a small but active pool of French surgical researchers. EMR 3738 belongs to these researchers, and its national and international reputation is outstanding, in large part because of the lifetime achievement of François-Noël GILLY in peritoneal carcinomatosis and his leadership as the President of the UCBL since 2012.

The integration of a surgical team with complementary approaches (chemotherapy and radiotherapy) in clinical cancer research is a strong asset. Over the last research contract period, EMR 3738 has received major public and industrial research funding, and is rich of expertise and resources. Accordingly, the unit has produced significant knowledge and achievements. However, innovative character of research (paradigm changes, breakthrough research) has been decreasing over time, world-class publications are largely missing in the very last years. With 35 researchers, EMR 3738 has the critical mass (including expertise and financial resources) required for successful research projects in the future.

However, the project presented for the next research contract period has not the quality expected. In order to be successful, the research project for the next contract period (2016-2020) should be re-designed, in particular focused and prioritized. This is true for Teams #1 and #3, and to a lesser degree also for Team #2. An active reflexion on potential synergies within EMR 3738 and with external partners should be initiated in order to generate additional value. Preclinical research programs should be urgently implemented as a precondition for future early-phase clinical studies. Organizational management (in particular coordination between clinical and research tasks) and processes (time management) should be improved. Integration of EMR 3738 into a larger cancer research structure in Lyon South might be a strategic opportunity. Team #3 should be monitored with particular attention.

Strengths and opportunities in relation to the context

Team #1 belongs to the leading groups in peritoneal cancer in France. Examples for this leadership are the National Reference Centre for rare tumors of the peritoneum, the National Reference Centre for trophoblastic tumors and large clinical databases such as the (BIG) RENAPE network for digestive tumors of the peritoneum. Team #2 has demonstrated superior expertise in theranostics based on body fluid biomarkers and mathematical modelization, and receives strong financial support from industry. This team received in 2010 the quality label for early-phase clinical studies (CLIP). Focusing on chemotherapy in the elderly patient is a valid strategic option.

Scientific output of both Teams #1 and #2 is significant; Team #2 has clearly increased this output over the last 2 years. Team #1 is well networked on international level, and has contributed to high-level publications within this framework.

A high number of doctoral students (Team #1, Team #2), training of external teams in France and abroad (Team #1, Team #3), participation to master programs (Team #1, Team #2), participation to collaborative projects between universities demonstrate a clear commitment to teaching. The creation of a patient association (AMARAPE) raising research funding is remarkable.

Weaknesses and threats related to the context

Team #1 is answering important clinical questions but the innovative nature of its research might be questioned. Lack of standards in several parameters such as disease definition, quality of surgery and tumor response assessment are and will remain intrinsic limitations of clinical research in peritoneal cancer. Randomized trials are exceptional in this research area, so that the level of evidence delivered (based mainly on registry studies) is not strong enough to compete with systemic chemotherapy studies. It is not even likely that comparative studies will deliver within the next 5 years the proof that hyperthermic intraperitoneal chemotherapy (HIPEC) has a significant effect on oncological outcome in addition to cytoreductive surgery alone, in particular for cancers with signet-ring histology and ovarian cancer. This represents a major threat for Team #1 in the medium-term and requires an alternative strategy for the next research contract.

Modeling disease evolution and therapy response using body fluid biomarkers is a valid and strong scientific project for Team #2. However, for these biomonitoring studies, Team #2 is essentially depending on sample and data collections provided by others. Against this framework, it appears critical that the number of collaborative publications with external partners is low and even decreasing over time. Team #2 has initiated a number of earlyphase clinical trials since 2010 but these efforts resulted in very few publications so far.

For Team #1 & Team #2: Preclinical research in the lab or in the animal is not developed enough, although such models are obviously available (rabbit; rodent). The need for such experimental research is explicitly recognized by the head of EMR 3738 and the corresponding resources are locally available, but the scientific project 2016-2020 is not prioritizing such preclinical research at all. For such studies, the choice is to collaborate with external partners. This might be explained by time constraints (the routine clinical duties of most of the team members limit the availability for experimental tasks) and missing expertise, but this is not acceptable: generation of preclinical data is considered critical by the committee since toxicity studies in two animal models are a regulatory prerequisite for investigator-initiated early-phase clinical studies Synergies between the 3 teams are claimed to be strong but this is not fact-based: only 8 common publications over the last 5 years (out of over 100 listed on PubMed) have been found by the committee (Team #1 with Team #2: 5; Team #1 with Team #3: 3). These figures (under 10 % joint publications) appear too low in an integrated research unit, with plenty of potential synergies.

Team #3 overall appears weaker in term of scientific output, and the publication focus is unclear for the auditors with over 50 publications "off field of research" during the period under observation. A striking observation is the lack of collaboration of Team #3 with other Teams of EMR 3738, in particular with Team #4, which appears a "natural" partner considering their field of expertise and their interest. The nature of this observation is irreversible as Team #4 will leave the unit EMR 3738 -a missed opportunity. The level of collaborations of Team #3 with external partners also appears to be low.

Recommendations

The committee recognizes the major achievements of EMR 3738 obtained during the last contract period in patient care, research and education.

However, traditional answers should be reevaluated in the light of future challenges and the committee proposes the following comments and recommendations that might help the Chairman to better prepare EMR 3738 for the future:

-to renew his personal spirit and vision as the head of EMR 3738 for the last years of his exceptional career, in order to ensure the sustainability of this research unit. This transition will include scientific, organizational, financial and human resources decisions; -to find ways to integrate EMR 3738 within existing regional cancer research structures, without losing the existing focus in clinical research. In particular, the criteria and process for selection of clinically relevant results from translational research programs should be defined; -against this framework, to reshape and precise the research program 2016-2020, in particular by: -proposing/selecting breakthrough research projects (new questions); -exhausting potential synergies between research teams #1 to #3; -refocusing and simplifying research activity on these projects; -addressing and mastering methodological limitations of research in peritoneal cancer; -to coach the Team leaders during the transition process (in particular Team #3).

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

	Doctoral students	13
	Theses defended	17
	Postdoctoral students having spent at least 12 months in the unit (PHU)	3
	Number of Research Supervisor Qualifications (HDR) taken	2
	Qualified research supervisors (with an HDR) or similar positions	23	20
		Number as at	Number as at
		30/06/2014	01/01/2016
	N1: Permanent professors and similar positions (PU et MCU)	21	18
	N2: Permanent researchers from Institutions and similar positions	1
	N3: Other permanent staff (without research duties)	6	6
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	(PrAss)
	N5: Other researchers (PHU, PH) (Emeritus Research Director, Postdoctoral students, visitors, etc.)	10	9
	N6: Other contractual staff (ARC, Biatss) (without research duties)	7	7
	TOTAL N1 to N6	45	40


3

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:

Pathophysiology of injury-induced immunosuppression Unit acronym: The proposal for the creation of a research unit was presented with research-groups with two different and complementary backgrounds: (i) academic field (clinical immunology and department of anaesthesiology and intensive care medicine, E. Herriot hospital, Hospices Civils de Lyon, HCL) (ii) diagnostic company (Institut Mérieux). Between both research groups a long-lasting collaboration exists since 2002 with the creation of a joint unit ("Laboratoire Commun de Recherche" -LCR). This research unit has been dedicated to the discovery of biomarkers in inflammatory contexts. Since 2008 the group focuses on sepsis induced immunosuppression.

Most of the future team's members come from the team "Haemostasis, inflammation, and sepsis", currently headed by Mr Claude NEGRIER. This team decided to split into three teams as the developed projects diverged. Therefore, team-members involved in research dedicated to sepsis decided to build a new team in collaboration with bioMérieux, the PI 3 .

The LCR is located in the E. Herriot hospital, as are the Clinical Immunology lab and Anaesthesiology and Intensive Care Medicine department of HCL. Thus, the LCR will constitute the core location of the PI 3 lab with 600 m 2 space.

Management team

The PI 3 will be managed by the scientific board which will include the four subgroup leaders (Ms Fabienne VENET, Mr Vincent MALLET, Mr Julien TEXTORIS, and Mr Guillaume MONNERET), Mr Alexandre PACHOT (director of the Medical Diagnostic Discovery department at bioMérieux), and Mr Thomas RIMMELÉ (Head of Anaesthesiology and Intensive Care Medicine department, E. Herriot hospital). This team will be headed by Mr Guillaume MONNERET. The group developed a high level translational research that aimed to decipher the aspects of immunosuppression induced by sepsis, essentially in intensive care units (ICU) patients. This topic has a high impact since septic complications remain the number one cause of death in ICU. This work is original and well recognized. This conclusion is supported by a quite large number of articles published in peer-reviewed journals, including 140 research papers, 10 review articles, as well as 33 invited lectures in international congresses and 5 patents in the last 5 years. The creation of the PI 3 research unit relies on a strong and sustained collaboration between bioMérieux and HCL. This collaboration has already proven successful in terms of patents, publications and grants. Moreover, the research group has been very active in training with 8 PhD students in the last 5 years. Working at the interface between academic and industrial institutions, the group profits financially from both worlds. In this respect, the estimated expenses of the group are covered by the REALISM project (IRT Biosater), which will provide substantial contribution for the next 4 years. Finally the group collaborates with innovative and well-established international research groups.

Strengths and opportunities in relation to the context

The research group has an impressive experience in clinical research with good access to patient samples and clinical data, which represents the basis for translational research. It focused on an original idea (sepsis-induced immunosuppression); its very good translational research allowed it to describe several biological prognosis markers.

The collaboration with an industrial group is very rewarding for both parties.

From a financial standpoint, the group will be able to cover the estimated costs for the next 4 years. The studies cover various areas in the field of sepsis attempting to address mechanisms of immunosuppression following sepsis from different perspectives. The findings of the proposed studies may result in clinical trials giving an opportunity for new therapeutic interventions in septic patients.

The group has established international collaborations.

Weaknesses and threats related to the context

The research focus of the group, immunosuppression and immunomodulation of sepsis and trauma, has been addressed by a number of research groups in the last decades, but did not have much clinical implication yet. In particular, clinical trial-attempts which focused on the modulation of single factors failed after promising results in experimental models.

Nevertheless, the topic is of great clinical interest. As mentioned above the research group addresses potential mechanisms of immunosuppression following sepsis from different approaches. The diversity of research aims within the proposal may represent a weakness but could also be considered as strength since this may result in innovative interacting projects.

  Mr Jean-Daniel LELIÈVRE, University Paris Est Créteil (representative of the CNU) Mr Jean-Louis VINCENT, Université Libre de Bruxelles, Belgium Scientific delegate representing the AERES: Mr Joost VAN MEERWIJK Representatives of the unit's supervising institutions and bodies: Mr Marc BONNEVILLE, Institut Mérieux Mr Denis FOUQUE, Université Lyon 1 Ms Marie-Claire MAZE, Hospices Civils de Lyon Sylvie RICARD-BLUM (represntative of ED n°205 "École Doctorale Inter-Disciplinaire Sciences-Santé" -EDISS) 1  Introduction History and geographical location of the unit

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  Overall assessment of the unitGlobal assessment of the unit

Recommendations

The research should emphasize commonalities between the distinct aspects of sepsis-induced immunosuppression proposed. This may help to enhance the benefit of the collaboration between the sub-groups and find fruitful interactions between the proposed studies.

Immunomonitoring, as suggested in the proposal, should be used as a platform for individualized therapy (personalized medicine) and as a basis for patient inclusion in clinical trials.

Research developed by the team is descriptive and the expert committee feels that it is important in the future to add in vitro mechanistic experiments or animal models. Finally, interaction with clinicians should be increased in order to develop trials initiated by the team. The group should be more directly involved in the conduct of trials rather than having an ancillary role of blood analyses.

Increasing the diversity of the patient populations should also be recommended. The planned study of patients after cardiac arrest is a good example.