Research units

In the name of HCERES,1

Didier HOUSSIN, president

In the name of the experts committee, 2 Alberto BRAMATI, chairman of the committee The french community of High Power-High Energy Lasers and Plasmas is structured around the "Institut Lasers et Plasmas" (ILP), which is in charge of defining a coherent scientific policy in this field. ILP is constituted by two operative structures: the « Fédération Laser et Plasmas » (FLP), created in 2003 and the "Association Laser et Plasmas" (APL). FLP has the aim to coordinate and promote the scientific exchanges among the french laboratories working in the field of high energy, high power lasers and plasmas generated by these lasers. On the other hand APL is in charge of the management of the CEA laser facilities (LMJ and PETAL).

The three structures are strongly interacting and they work coherently in a fruitful collaborative way, facilitated by the fact that ILP and FLP have the same director and that the co-director of ILP is also the president of APL.

FLP presents an internal organization, divided in two poles: the "HDE" focused on the activities dealing with high energy lasers (relatively long pulses of hundreds of picoseconds, nanoseconds), and the "UHI", devoted to the high intensity laser, with ultra short pulses (femtoseconds up to tens of picoseconds).

The FLP regroups teams from nineteen different departments with a large spectrum of research activities, both experimental and theoretical. The number of researchers associated to the federation, with a variable degree of involvement, ranges from 250 to 300 people.

Management team

The FPL is headed by Mr Patrick MORA (CPHT, École Polytechnique), assisted by Mr Dimitri BATANI (CELIA, Université de Bordeaux), responsible of HDE pole and by Mr Philippe MARTIN (IRAMIS/LIDyL, CEA), responsible of UHI pole.

Personnel

None.

 Assessment of the federation

Global assessment

The FLP plays a central role in the coordination, scientific animation and support of the research activities of the french community in the field of intense lasers and plasmas.

The main activity of the federation consists in the organization of a regular conference (the Forum ILP) every 18 months (on one week), attended by a large number of members of the federation (typically one third of them). These meetings, in which the main french actors in the field are represented, constitute a precious opportunity to boost the scientific exchanges and to highlight the recent relevant achievements inside the french community. It is worth to note that during these meetings a significant number of talks (about 40%) are given by PhD students and post-docs; this is certainly an important contribution to the training of young researchers and to the improvement of their communication skills.

The FLP also organises thematic workshops (on average three per year) and provides financial support for conferences co-organised by members of the federation and for visits and short stays in laboratories of the federation or even abroad.

Another important instrument for the scientific communication inside the FLP is the publication, quarterly, of an information letter containing all the relevant news concerning the domain of activities covered by the federation.

The FLP organises the calls for the access to the CEA/CESTA facilities and is in charge of the selection process, insured by a specifically nominated scientific advisory committee.

Finally the FLP plays a central role of expertise at the national level, with delivery of (i) scientific documents guiding the future users of the new french laser facilities and (ii) prospective reports defining the long-term requirements of experimental developments for the communities of intense lasers and plasmas physics.

In summary FLP is a dynamic light structure, with an efficient management, performing important federative activities for the scientific community involved in laser and plasmas physics. This task of expertise, melting and communication deserves to be supported and encouraged.

Strengths and opportunities

The variety of the topics addressed by the laboratories of the federation is extremely wide and its coordination action is of great importance to insure a global vision and coherence among the different activities.

The interactions and collaborative works between members are facilitated in the framework of the federation.

This management appears also useful to define the strategic axes for the future development in the field.

The links and collaborations with the international community are well established and contribute to further increase the visibility of the french activities, which is of major importance in this very competitive field.

Weaknesses and threats

The federation carries out its activities with an annual budget that is quite low (40 k€), mainly provided by CNRS (75%) and École Polytechnique (25%). Note that it will suffer of a reduction of about 30% for the next year. With these limited resources it could become a very challenging task to maintain and reinforce the role of animation and organisation of the scientific community, especially taking into account the strong involvement that the federation is expected to play in the new facilities (LMJ, PETAL, APOLLON) that will be operative in a near future.

Recommendations

It is important to pursue and reinforce the present effort of coordination and organization of the laser and plasmas scientific community.

A further increase of the collaborations and interactions between the different laboratories would be beneficial to the whole community. This could be obtained incrementing the support provided by the federation to the circulation of researchers among the different associated laboratories.

To reinforce the international links, it would be helpful to promote the participation of foreign scientist to the ILP Forum, for example by inviting some eminent scientist who could deliver invited talks highlighting the major results obtained worldwide.

The committee must finally stress the importance of preserving and possibly increasing the budget to maintain the key-role of FLP at its present level. To strengthen its federative role in a complex financial context, a viable strategy could be to gather (modest) contributions from each FLP partner to support collaborative projects between teams of different departments.

  Under the decree No.2014-1365 dated 14 november 2014, Federation Name of the federation: Fédération de Recherche Lasers et Plasmas Acronym of the federation: , Université Pierre et Marie Curie Scientific delegate representing the HCERES: Ms Sylvie MAGNIER Representative of the unit supervising institutions and bodies: Ms Pascale ROUBIN, CNRS 1  Introduction History and geographical location of the unit

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)


president Michel Cosnard

Guillaume Pinna

Federation

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.

Federation name:

Biologie, Santé et Innovation, Technologique  High-throughput core facilities: Health genomics, Expert annotation of gene and genome -Amadeus, Imaging for cell content analysis -ImPACcell.



Protected areas experiment core facilities: Animal housing facility A1, A2, A3 -ARCHE, and L3 cell culture facility.

The majority of the scientific equipment has recently been purchased, ensuring state-of-the-art analytical capabilities.

BIOSIT pursues a triple mission consisting in the federation of the research teams, the management and development of high-tech core facilities and the establishment of partnerships with the local economic network. To realize this mission, BIOSIT actions are: These missions and actions are carried out for the benefit, in priority, of the research units and teams that contribute to the federative structure, and are aimed to promote excellence in research and provide national and international visibility to Rennes laboratories.

Most of the facilities are developing R&D programs in their field of competence to expand their know-how and provide innovative services to their collaborators. Several of these developments have been patented (notably by the MRic, NLMRP & H 2 P 2 facilities).

Altogether, BIOSIT is a comprehensive structure providing mutualised scientific technologies and services, with locally and, for some platforms, nationally & internationally recognized know-how.

BIOSIT was evaluated by a committee of three experts. Each was a member of the visiting committees of three unit members of the SFR. The selected research units were 1) the Chemistry Oncogenesis, Stress, Signaling laboratory (COSS, Inserm), 2) the Institute of Genetics and Development of Rennes (IGDR, CNRS and the University Rennes 1) and 3) the Research Institute for Environmental and Occupational Health (IRSET, Inserm, EHESP, University Rennes 1, University of Angers).

Management team

Since 2012, Mr Thierry GUILLAUDEUX is the director of the BIOSIT SFR. He is assisted by an executive board composed of Mr Michel SAMSON (DR2, IRSET), Ms Christelle CHAPRON (executive secretary, UMS/US BIOSIT) and Mr Alain FAUTREL (Engineer Staff Representative, INSERM UMR 991). For the next 5-year period, Ms Nathalie DEJUCQ-RAINSFORD (IRSET) will be proposed as vice-director in replacement of Mr Michel SAMSON who will become co-director of ISRSET in 2017 Specific workforce allocated to the federative structure

The managerial, administrative, scientific and technical staff represents 30 people, mainly from the Rennes 1 University. Sixteen people benefit from a permanent position (1 permanent lecturer, 1 permanent researcher, 18 engineers, technicians and supporting staff) and 14 are employed with limited duration contracts. Additionally, member units provide BIOSIT with 38 people.

2  Overall assessment of the federative structure Global assessment of the federative structure

The BIOSIT SFR has emerged as a highly performing scientific and technical pole, providing a broad range of techniques to a large community of researchers. It initiated successful scientific and technical interactions between the member units, and plays a key role in connecting platforms and academic laboratories with industrial partners. As such, BIOSIT strongly contributes to promote excellence in research, and confers national and international visibility to the Rennes laboratories.

BIOSIT is remarkably well funded, allowing maintenance and renewal of the scientific equipment. It has a federative role for private and academic research groups, but also with other partners involved in the Health & Biology sector. BIOSIT's positive impact on research has been demonstrated by the quality of the scientific output of the contributors that benefited for the structure's support.

The training of students and research personnel is satisfactory and guarantees a facilitated access to the proposed techniques and services. Seminars on topics of general interest are regularly organised throughout the year to present the impact of BIOSIT -or to introduce emerging technologies to the scientific community.

Yet, BIOSIT is today at a critical step in its development. Despite most of the equipment being state-of-the art, some specific facilities have aging machines, and show difficulties in stabilizing their technical staff. The Committee feels that, at mid-term, these issues could challenge the continuity of BIOSIT development.

Strengths and opportunities in the context

BIOSIT has grown as a scientific and technical pole of excellence that answers a broad range of regional and national technological needs in biology. It also has very strong interdisciplinary interactions with the academic and private sectors in the French west region. As an illustration, during the last 5-year period, BIOSIT is behind the creation of a joint Laboratory between a private company (Biotrial Pharmacology) and a research laboratory funded by ANR (LabCom). Also, BIOSIT offers facilities for emerging start-ups and innovative companies.

BIOSIT's facilities have highly skilled and specialized scientific and technical staff, who are involved in the daily running of the platforms, but also in research and innovative technological developments in their field. These are attractive assets to interact with the local & national private sector, and establish long-term partnerships that would help sustain the structure's funding. Also, many research teams in biology, and notably in cancer research, are located in Rennes, and the existence of a shared federative structure of core facilities could be an additional mean to consolidate the scientific exchanges between these various groups.

A sustainable financial and strategic support from the involved partners should provide to BIOSIT a proper environment to thrive and maintain a technological offer of the highest standards, given that a critical mass of permanent personnel is achieved in a near future.

Weaknesses and threats in to the context

The impressive size of BIOSIT may lead to inadequate decisions with regard to the scientific needs of local teams. Also, sustainment of an appropriate funding for all the platforms is highly dependent on external partners and on the economical context. Therefore, the directing board should be able to secure funds to anticipate any potential budgetary failure in the short and medium run.

A major threat, already identified by the BIOSIT board, concerns the human resources of the facilities: most of the technical personnel are recruited on short-term contracts, and few permanent people are fully affected to the facilities. At very short term, the high turnover level of the technical staff (as attested by the amount of departures & arrivals in the past 5 years) could impact the viability of the affected facilities, or, at least, their capability to maintain a high degree of specialization and/or answer to ambitious projects. Additionally, the BIOSIT total staff comprises 68 personnel with 38 persons who are provided by member units: although it's an essential contribution, this can lead to a human resources management major problem.

Two other main threats may be the disengagement of trustees (INSERM, CNRS) and the obsolescence of expensive equipments with the need to renew them.

Another concern relates to bioinformatics needs: BIOSIT concentrates a significant amount of high-throughput and imaging platforms that probably generate heavy weighted files and/or large datasets as outputs. As most of these platforms expect an increase in their activity in the 5-year plan, either by acquiring new equipment or by broadening their service offer, important data storage and analysis needs may arise in the near future. Some platforms have dedicated bioinformaticians, but not all of them (e.g. ImPACcell), which may pose a threat to the efficient running of these facilities.

The valorisation of the scientific and technical results obtained by the platforms could be enhanced. As such, one concern of Thierry Guillaudeux is to raise member units' awareness of the importance for BIOSIT members / platforms to be cited in publications (co-authors, acknowledgments).

Recommendations

The BIOSIT SFR has succeeded in the structuring and the development of 14 high-level platforms by mutualising human resources and equipments with the support of member units. The excellence of BIOSIT core facilities and their profound impact on the research programs of the partner laboratories, the adequacy of the offer with the team's needs, the (so far) sustained funding and BIOSIT staff mobilization justify to support this federative structure in every way possible for the years to come. This support should be both financial and strategic, to conduct a sustainable and active policy in order to ensure BIOSIT development in three main areas: recruitment and perpetuation of its own staff, infrastructure development and investment in state-of-the-art equipments.

Attributing full time permanent positions to the facilities with the highest personnel turnover, and/or anticipating long-term technological developments, should be considered as a priority.



  to share, manage and develop state-of-the-art technological platforms;  to support and develop Research & Development projects on platforms in relation to the research units;  to develop industrial partnerships in relation to the units;  to insure a scientific coordination within the transversal themes;  to promote support for research;  to develop international collaborations.

  IntroductionHistory and geographical location of the federative structure and its member research units and brief description of its activities.Located in Rennes, BIOSIT is a Biology and Health Federative Research Structure (SFR). It is also a joint unit of services recognized by the University Rennes 1, CNRS (UMS 3480) and Inserm (US 018). Managed by Mr Thierry GUILLAUDEUX (Associate Professor, University Rennes 1) since the 1 st of January 2012, BIOSIT brings together 12 research units corresponding to 54 research teams and nearly 750 people. All the BIOSIT member units belong to the University Rennes 1 and/or Inserm, CNRS, INRA, the French School of Public Health (EHESP) and the French Blood service (EFS). Moreover, BIOSIT has other partners such as the Centre de Lutte Contre le Cancer, the Rennes University Hospital and the University Rennes 2.BIOSIT mutualises high-end equipments and staff within 14 technology platforms providing a broad range of scientific and technical expertises. These platforms are grouped in four core facilities:

	Federation acronym: Label requested: Present no: Name of Director (2015-2016): 1   Resources core facilities: Biological Resources Center (CRB)-Health, Zebrafish and Mice transgenesis BIOSIT SFR SF 4206 Mr Thierry GUILLAUDEUX
	Name of Project Leader (2017-2021): platform, EFS National Laboratory of Monoclonal Reactive Production (NLMRP). Mr Thierry GUILLAUDEUX
		Tissular, cellular and molecular analysis core facilities: Microscopy Rennes Imaging Center -MRic, Bio-
		RMN and Bio-SCANs (PRISM), High Precision Histopathology (H²P²), Flow cytometry and cell sorting,
		Spectroscopies.
	Expert committee members
	Chair:	Mr Guillaume PINNA, CEA SACLAY, Gif-sur-Yvette
	Experts:	Mr Vincent DIVE, SIMOPRO, Gif-sur-Yvette
		Mr Benjamin GILLET, IGFL, ENS-Lyon
	Scientific delegate representing the HCERES:
		Mr Pierre COUBLE
	Representative of supervising institutions and bodies:
		Mr Claude LABIT, University Rennes 1


Federation

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.

Federation name:

Interactions Cellulaires et Applications Thérapeutiques History and geographical location of the federative structure and its member research units and brief description of its activities.

The Research Federative Structure (SFR) FED4208 "Interactions Cellulaires et Applications Thérapeutiques" (ICAT) was created in 2012, as a continuation of the federative institute IFR132 which had the same title, had been created in 2004 and renewed in 2008. The SFR ICAT belongs to the University of Angers and has also a partnership with the CHU ("Centre Hospitalier Universitaire") of Angers. The nine other units are geographically located on one single site (Angers). In terms of human resources, all these different research units represent about 300 researchers supported by 70 technicians and administrative staff. All the 10 research units are members of the "pôle de compétitivité atlanpole biothérapies" and 2 of them are integrated in a "Laboratoires d'Excellence" (LabEx).

The research units share scientific equipment, available through 4 technological platforms and 2 common service facilities. These facilities are dedicated to imaging and microscopy (SCIAM, Service Commun d'Imagerie et d'Analyse Microscopique), molecular and cellular analysis (PACEM, "Plateforme d'Analyse Cellulaire Et Moléculaire"), radiobiology and experimental imaging (PRIMEX, "Plateforme de Radiobiologie et d'IMagerie EXpérimentale"), production of lentiviral vectors (lentivec, "plateforme de production de vecteurs lentiviraux"), functional imaging applied to biology and medicine (CIFAB, "Centre d'Imagerie Fonctionnelle Appliquée en Biologie et médecine"), and animal housing and availability for experiments (SCAHU, "Service Commun Animalerie Hospitalier Universitaire").

The research programs coordinated by the SFR ICAT have been developed along 3 axes: -i) cardiovascular and metabolism, -ii) nanomedicine and biomaterials, and -iii) immunology/infectiology & cancerology.

Management team

The management team is composed of Mr Vincent PROCACCIO, the current director, and Mr Pierre ABRAHAM, the project leader and the future director. Both are PU-PH, and members of the research unit "Biologie Neurovasculaire et Mitochondriale Intégrée » (BNMI), one of the research units of the SFR and of the CHU of Angers. The director is appointed by the University of Angers. The management team is assisted by a board of officers. In addition, an operational unit is proposed to be created to further strengthen the role of support and service of the structure.

Specific workforce allocated to the federative structure

Nine people are employed in the SFR: two technicians and three engineers involved in running the platforms and training new users, two secretaries for administration and budget management, a biostatistician to help in the analysis of biological data, and a project engineer devoted to technology transfer. Six of them are employed by the University of Angers, two by INSERM and one by the CHU of Angers. It must be noted that a person was recruited in 2012 and that four new positions were opened in 2013 (2) and 2015 (2) in the structure (a technician, an engineer, a biostatistician, a project engineer) 2  Overall assessment of the federative structure Global assessment of the federative structure

The overall assessment of the federative structure ICAT is very positive. With no doubt, the SFR ICAT represents a key element for the University of Angers, providing strength, visibility and leadership to the local biomedical research. Overall, the majority of the challenging objectives set for the period 2010-2015 in the frame of the last contract have been, or are in a good way to be, reached. Among the successfully reached objectives, one may cite the identification of federative research thematics, which resulted in the consolidation of existing teams -or allowed the emergence of new ones -grouped together inside a common geographic cluster, as well as the development of the technological platforms and common services and their inclusion into a defined strategy, and facilitated the regional structuring of research and integration of two units (MINT and CRCNA) into a LabEx. All these efforts are strongly supported locally, by both the university and the CHU of Angers, notably through the improvement of laboratory space (a new building being under construction) and a clear administrative investment to strengthen the personnel assigned to the SFR.

Strengths and opportunities in the context

During the last five years, the SFR ICAT has developed and amplified the strengths that had emerged during the previous contract. Three of them can be cited. First, and most representative, is the effective federation of high quality scientific teams. Of note is the important structuring role played by the SFR in the efforts undertaken in 2013 to regroup and concentrate the research projects developed by the research teams into three axes, leading to a better visibility and an increased scientific dynamic (1246 publications, 36 patents, 3 start-ups, 10 M€ of funding). In this regard, the scientific animation is also an essential component of the activity of the SFR. The second strength is the set up and sharing of modern technological platforms and of efficient common facilities. For example, a platform (CIFAB) dedicated to in vivo small animal imaging was created; and in another one, (PACEM), the offer of molecular and cellular analyses was improved and has integrated in addition the production of lentiviral vectors and the analysis of mitochondrial physiology. The activity of these two platforms resulted in at least 20 publications. The existing common services SCIAM and SCAHU were also improved and their activity has resulted in their participation in 26 publications. Finally, the third representative strength is the strong interaction of the SFR with the regional socioeconomic environment.

Weaknesses and threats in to the context

No significant major weaknesses or threats are immediately apparent. However, a possible threat could come from the limited number of human resources specifically allocated to the SFR. This may notably affect the optimal functioning of the platforms and, in the mid-or long term, make the ambitious goals proposed for the next five years, difficult to reach.

Recommendations

Given the successful results obtained during the last five years, which come from the optimal efficiency of the SFR, care must be taken not to break the impetus and continue the efforts. The visibility gained at the local level should be confirmed at a regional level and extended, if possible, nationally and internationally. This would contribute to the attractivity, and help to recruit talented researchers or new units from around the world. Regarding platforms and common services, their improvement, both in terms of instruments and of management, should be considered as a priority. Specifically pertaining to the federative activity, the SFR should now put sustained efforts to reinforce the interactions between the different partners (University of Angers, CHU of Angers inter alia) with the aim of setting up transdisciplinary programs. Last but not least, regarding the evolution of the SFR toward a status of UMS, the pros and cons of each type of structure (SFR vs UMS) should be carefully evaluated and compared, notably with keeping in mind the distinct missions and objectives attributed to each of this type of research support structure. The committee is concerned that switching from an SFR to an UMS label will, per se, destabilize or even stop the federative dynamics, and considerably reduce the current and the future ambitious missions attributed to the SFR, by restricting them mostly to only technological and common services.


president Michel Cosnard

Federation

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.

Federation name:

Institute of Research and Innovation in Biomedecine History and geographical location of the federative structure and its member research units and brief description of its activities

The IRIB, "Institute of Research and Innovation in Biomedecine" was created in 2012 by several units that decided to share their respective equipment and human resources. This federative structure is supported by the University of Rouen, the CHU of Rouen, the CNRS, the Inserm, the regional council of "Haute Normandie", the Henri Becquerel Center. It includes several platforms and facilities: flow cytometry (material and equipment from the INSERM U905), cell imaging, genomic and proteomic, animal's facilities with animal behaviour analysis and small animal MRI.

IRIB has also set up an oxidative stress analysis facility.

At present, the platforms are used by 19 Inserm, CNRS, University and hospital structures.

IRIB, as a regional research network, has been supported by the Normandy region and the ERDF European program. Three IRIB platforms, PISSARO, PRIMACEN and SCAC, have obtained the IBISA label.

Management team

The management team consists of the direction and an executive committee. Each month, the executive committee, with representatives of every unit, meets to decide on the investment policy, the organization of meetings and presents the financial report.

Specific workforce allocated to the federative structure 6 engineers (5 Inserm and 1 CNRS, 3 with HDR) are allocated to the federative structure; one of them is also helping the director (50% of his time). Historically, it was stated that they are devoted to the platforms and to the director unit in charge of the IRIB.

The other people of the workforce at IRIB are affiliated to different research units and work part time for the platforms.

2  Overall assessment of the federative structure Global assessment of the federative structure

The assessment of the IRIB platforms is very positive. Indeed, this platform has been a great support for the laboratories of the Normandy region and has brought a major technical help within the biomedicine domains and the chemistry departments. It played a complementary role with the other neighboring platforms and has, thus, contributed to open and extend the analytic area.

Moreover, the executive committee anticipated the fusion of the two regions of Normandy by initiating a fusion project with the federative structure ICORE. The platform will play the same role in this new setting.

Strengths and opportunities in the context

The federative structure offers all the facilities for biomedical and biological research and mainly for the priority scientific axes of the region.

One of the major strengths is its training program. Approximately twenty students followed a training course in imaging. Most of them found a job after the training either in a private company or in public institutions including platforms.

IRIB organized 5 national and 5 international congresses (Congrès du Groupement Français des Peptides et Protéines, 17 th International Symposium on Chromaffin Cell Biology …) and contributed to classes as "Formation permanente" by specific workshops and schools (Journées Scientifiques du réseau LARC-Neurosciences …).

An Inserm member assigned to the PRIMACEN platform has developed a new laboratory software, Easy Lab Manager, which will be distributed to all Inserm units.

The ambition of the project is in adequacy with the available budget.

Weaknesses and threats in to the context

The visiting committee did not identify particular weakness except the fact that only a few private companies use the federative structure (approximately 5% but they contribute to 20% funding), but this is the case with the vast majority of French core facilities.

Recommendations

 Maintain the coordination established in Rouen towards the entire Normandy region;

 improve the scientific priorities by the scientific council in order to target future actions;

 pursue the complementary actions with the other platforms of the region;

 improve the development of the web site to make more visible the actions/opportunities put together by the IRIB platforms, mainly regarding the equipments;

 strengthen the position of IRIB as an interlocutor and partner for financial support from the region and Europe.

  Ms Yolande RICHARD, Institut Cochin, Paris (representative of the INSERM) Mr Cassian SITARU, University of Freiburg, Germany Scientific delegate representing the HCERES:


The visit took place on the afternoon of December 22nd, 2010. It started with two presentations followed by a general discussion by the previous and the proposed directors, who presented the report over the previous contract period and the project for the next one. This was followed by a discussion with the representative of the University of Caen Basse-Normandie. Next, the commission spoke with the students and postdoc currently present in the laboratory and, finally, with the technical and administrative personel. The last part of the afternoon was reserved for a closed meeting of the comittee during which the first conclusions of the visit were formulated.

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

The research unit "Groupe Mémoire et Plasticité comportementale" (GMPc) is localized at the University of Caen Basse-Normandie. It was established by the fusion of the EA3211 (Laboratoire de Physiologie du Comportement des Céphalopodes) and part of the EA3915 (Centre d'Etudes et de Recherche sur le Médicament de Normandie) in order to form a team with a clustered expertise in the fields of behavioral neuroscience, neuroethology and neuropsychopharmacology. This reorganisation resulted in a team of 10 enseignants/chercheurs with 4 full professors and 6 assistant professors (maîtres de conférences), with a total of 7 scientists having obtained the HDR. The unit is part of the UFR des Sciences Pharmaceutiques and the Institut de Biologie Fondamentale et Appliquée at the University of Caen Basse-Normandie. Furthermore, the unit is embedded into the IFR (Institut Fédératif de Recherches) and ICORE (Interactions Cellule-Organisme-Environnement, 2008-2011) and since 2009 they also benefit from the plateau technique du CURB (Centre Universitaire des Ressources Biologiques). The unit also participates in the marine station UCBN in Luc sur Mer and the CREC (Centre de Recherches en Environnement Côtier).

Currently the unit is split in 3 locations. Members of the unit work at facilities of the former CERMN (Centre d'Etudes et de Recherches sur le Médicament de Normandie) at the rue Vaubénard, at the GRP at the rue E. Zarifian, and finally at the Station Marine in Luc sur Mer.

In the past the team has developed a test battery to assess different types of memory including episodiclike, spatial, short-, and long-term memory. Another research line of the unit is the analysis of imprinting and embryonic learning and memory performance in cuttlefish. Still another research focus lies in the analysis and pharmacological treatment of memory deficits in the course of healthy aging and in the aim to identify behavioral-and or biomarkers to predict the risk for memory deficits in the course of aging. Finally another line of research is dedicated to the evaluation whether serotonin-related drugs might be able to ameliorate memory deficits in animal models of aging and schizophrenia.

The project has been streamlined and is organized appropriately along 2 main lines of research in the field of behavioral neuroscience. Each scientific topic will involve a multidisciplinary approach (neurobiology, neuropharmacology, genetics, behavior). These 2 main lines refer to i) the early determinants of behavior and brain plasticity and to ii) aging and the contribution of different sub-types of serotoninergic receptors to cognitive impairments in senescent animals. To achieve their goals, complementary methodological approaches will be used. The cuttlefish and the mouse will serve as animal models. In addition, all members of the group are strongly involved in teaching activities.

• Management team

The group will be directed by Ludovic Dickel and two leaders of the projects A and B will serve as deputydirectors.

• Staff members (on the basis of the application file submitted to the AERES) 2 Overall appreciation on the research unit

• Summary

This group has a substantial expertise and background in experimental psychology, animal behavior, neurobiology, and neuropharmacology. Under the leadership of the past and future directors of the unit, the research program has been streamlined and has become much better focussed than was the case in the past. The project is realistic and the goals set are certainly attainable. If the expected results do indeed materialize, it may be expected that some of these results will be publishable in general, high-impact journals. The originality of the project is very high: not many groups investigate the perinatal phase and the cuttlefish is a unique model. The Unit is composed of enthousiastic members, an important quality to do research, however, the universities should take into account that for research at a high level, it is important to discharge people from too much teaching, expecially a unit constituted only of teaching researchers ("enseignants-chercheurs").

• Strengths and opportunities

The GMPc has an excellent level of expertise in the different approaches and animal models used. A very strong point is the originality of the approach. Worldwide, few research groups use the cuttlefish as a model and even fewer integrate work on this model organism with work done on the mouse. In addition, the GMPc aims at deciphering a well-balanced combination of fundamental and clinical questions.

The investigation of imprinting, age-related learning, and memory mechanisms as well as episodic-like memory in cuttlefish is a very interesting and highly original research line and might be a distinctive and wellrecognized feature of the unit in the future. If successful, the intended research on episodic-like memory in cuttlefish could provide important insights into the evolutionary origins of the episodic memory system and would help to solve the still ongoing controversy whether episodic memory is indeed uniquely human and why it has been developed by humans only.

The research focus on the pharmacological treatment of aging-induced memory impairments is an active area of research which is currently well recognized by the public, is well funded, and due to demographic and socio-economical factors will surely gain in importance in the future. Thus these lines of research as proposed in the current application are very appropriate and timely. The combination of fundamental and clinical approaches is another strong aspect of the project, offering the possibility to reinforce and expand existing contacts with the pharmaceutical industry.

The unit has a well-planned recruitment policy. It has been reinforced by an expert in the field of molecular biology (Dr. E. Païzanis joined the team in September 2009) and an assistant-ingénieur for biological techniques in October 2010. It is planned to recruit an additional enseignant-chercheur with expertise in molecular pharmacology and, if possible, electrophysiology, in the future. These additional staff members will broaden the methodological repertoire of the unit and will enable the unit to investigate neurobiological mechanisms underlying behavioral effects.

In the past contract period, the unit published 53 articles in excellent international journals (mean impact factor = 3.6). This is equivalent to an average of 1-2 articles per enseignant-chercheur and year. This high level of productivity and scientific performance is the more remarkable given the many teaching and administrative obligations of all team members. In addition, the international visibility of the unit is very high, as shown by regular invitations abroad.

The GMPc organizes a regular series of internal seminars and journal clubs, ensuring that all members of the unit are in regular contact, despite the divergent geographical locations.

In 2011 the unit will move to a new facility which will presumably provide more appropriate and better working conditions, which hopefully will help the realization of more sophisticated research projects and to expand collaborative work with the pharmaceutical industry.

At the academic level, the team seems well inserted in the local and national teaching institutions (master level), ensuring the ongoing recruitment of well-trained Ph.D. students.

In addition to the research activities, the unit has participated in teaching at different levels. Members of the unit were in charge of UEs and DUs. They were active in teaching at the levels of Licence and Masters professionnels at the universities of Caen and Rouen, as well as the IUT de Caen.

• Weaknesses and threats

Although the new facility that will become available in 2011 is a potential strength and a great opportunity to reinforce ties between the until now geographically-separated members of the team, the move is also a potential risk and should be carefully planned, in order to minimize down time and time loss.

The unit has been relatively successful in obtaining funding in the past 4 years (one ERANet and one ANR grant) and should be encouraged to continue these efforts.

Up till now, the unit has not succeeded in attracting foreign post-docs or research stays by colleagues from abroad of more than a very short duration.

• Recommendations

The unit should increase their admittedly already extensive efforts for raising external funds. Specifically, the unit should try to increase its participation in international consortia enabling it to compete for international (viz. European) grants.

A main focus should remain a close collaboration with industry to develop a new class of ligands (agonists and antagonists) of the 5HT receptors under investigation.

The unit should profit from its high international visibility to recruit foreign post-docs and to host more international researchers for shorter or longer stays.

The unit should have more time to do rechearch correctly and competetively with other laboratories that have people doing research full time (i.e., the university is encouraged to reduce the administrative and teaching duties of the members of the unit). The main scientific contributions during the past 4 years are: (i) the development of behavioral paradigms to investigate episodic-like memory, spatial memory, long-term memory, and early learning in rodents (rat, mouse) and cephalopods (cuttlefish) (ii) the characterization of the neurobiological substrates supporting these different forms of memory (iii) the development of pharmacological and non-pharmacological approaches to investigate age-related memory disorders (iv) the development of tools to modulate the functional activity of some sub-types 5-HT receptors (5-HT4, 5-HT6 and 5-HT7).

The group has identified interesting topics. The results are well exploited and have already led to good publications in excellent journals. International collaborations have emerged from some results.

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

The large participation in teaching at the local and national level increases the visibility of the team projects for future students. Despite the large teaching load of the unit, a significant effort should be made to recruit foreign post-docs.

During these last 4 years, the group has published over 50 peer reviewed publications, which is an excellent level of production, especially given the large teaching load of the members of the group. These articles appeared in international peer-reviewed scientific journals with a mean impact factor of 3.6, which is considerable for a group mainly involved in behavioral work.

The team has a number of excellent local, national and international collaborations. Local and national cooperations exist with the Cervoxy team and INSERM U919 unit in Caen with Dr. Bernaudin, Dr. Touzani and Pr. Dolfus (UMR6232, CI-NAPS, Cyceron) and with Drs. Simmler-Lackenbacher and Galli (UMR 7592 CNRS, Paris), as well as Dr. Billard (U894, Paris). Furthermore, cooperations exist with Pr. Schaal (Centre Européen des Sciences du Goût Dijon), Dr. Hausberger (UMR 6552 Ethos Rennes I), Dr. Bonnaud (UMR 7208 Muséum National d'Histoire Naturelle et Institut des Nanosciences UMPC, 7588, Paris). International collaborations exist with Dr. Burt (Univ. Oxford, Royaume-Uni), Pr. Chiao (National Tsing Hua University, Hsinchu, Taïwan), Dr. Reneman (Department of Radiology, Academic Medical Center, Amsterdam), Dr. Gsell (Biological Imaging Center, Imperial College, London), Pr. Lucassen (Swammerdam Institute for Life Sciences, Amsterdam) and Dr. Adriani (Istituto Superiore di Sanità, Rome). There are also international cooperations with scientists from the University of Millersville, USA and University of Okinawa, Japan to study embryonic learning and memory performance and with Dr. Hochner from the University of Jerusalem in Israël to perform electrophysiological studies. Especially these international collaborations have a great potential in terms of attracting high quality postdocs, and even researchers, in the future, as well as attracting external funding, and establishing high quality links with local as well as international groups.

• Appreciation on the management and life of the research unit

The existence of internal seminars series and journal clubs is a strong aspect of the life of the research group. It serves as key opportunities for junior researchers and students to gain experience and hone their presentation skills.

Unit meetings are held approximately 2 times a month. These meetings serve to maintain internal communication and discussions, which is otherwise difficult to do due to the geographic distance between the 3 different locations. Within these meetings, progress reports about currenly performed experiments or proposals for novel projects are presented and discussed. There is also discussion about methodological issues and general issues and on topics important for the entire unit. Some of these meetings are dedicated to talks given by invited local and foreign scientists.

• Appreciation on the scientific strategy and the project Overall this is a very strong research project aimed at the functional characterization of several forms of memory in cuttlefish and rodents. One of the primary themes is understanding the functional contribution of 5-HT to perinatal spatial and episodic-like memories, using basic and clinical approaches.

There is excellent integration and a sharing of competences.

• Conclusion : Summary

The group will be led by an established investigator who has already been successful as a team leader. This group appears to be able to carry out behavioral neuroscience research at the highest level. The different participants are well positioned within the group and their expertise and research methodologies are complementary.

Strengths and opportunities

The group has very interesting experimental models, strong projects, and the required expertise to conduct them. The main strengths of the group lie in the strong behavioral and psychopharmacological background of its members, the complimentarity of the scientific questions addressed, and the integration of neurobiological research with high-quality behavioral work.

Weaknesses and threats

The number of PhD students is limited and more post-doctoral researchers would be advantageous for the further development and visibility of the unit.

Given the diverse interests of the group members, centrifugality could be a significant risk and should be continued to be guarded against. The track record of the unit in this respect gives confidence that this risk will remain limited.

Recommendations

The project would benefit from some further tightening and a modest reduction of the number of planned subprojects. Furthermore, reducing time devoted to teaching and increasing time devoted to research for each individual should be a priority. Finally, the unit is encouraged to continue its considerable efforts in funding raising.

••

  Production results A1: Number of permanent researchers with teaching duties (recorded in N1) who are active in research 10 A2: Number of permanent researchers without teaching duties (recorded in N2) who are active in research 0 A3: Ratio of members who are active in research among staff members [(A1 + A2)/(N1 + N2)] 100% A4: Number of HDR granted during the past 4 years (Form 2.10 of the application file) 3 A5: Number of PhD granted during the past 4 years (Form 2Appreciation on the results

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%
	*
	Intitulé UR / équipe	C1	C2	C3	C4	Note globale
	GROUPE MÉMOIRE ET PLASTICITE COMPORTEMENTALE (GMPC)	A	A	A	A	A

C1 Qualité scientifique et production C2 Rayonnement et attractivité, intégration dans l'environnement C3 Gouvernance et vie du laboratoire C4 Stratégie et projet scientifique 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


Report 1 Introduction

This review reports the evaluation of the research unit "Inhalothérapeutique des accidents de décompression" by the visiting committee mandated by the AERES. A manuscript has been sent to all committee members including the AERES delegate (Dr Bruno BONTEMPI, Institut des Maladies Neurodégénératives, Bordeaux, France), the chairman (Prof. Lucien BARTHÉLEMY, Professeur Honoraire) and the three experts (Prof. Yoram GROSSMAN, Ben-Gurion University of the Negev, Israel; Dr Daqing MA, Imperial College London, London, United Kindom; and Dr Philippe DE DEURWAERDÈRE, University Victor Segalen, Bordeaux, France, also corresponding member of the national council of the Universities, Neurosciences Section). The manuscript included a research report for the period 2006-2010 for the two research teams at the origin of the project. The scientific project was presented in the second part of the document followed by the curriculum of the individuals participating to the project according to the guidelines of AERES. The manuscript was written in English (except administrative parts in French).

• Date and execution of the visit

The visit took place on March 1, 2011 at the «Institut de Médecine Navale du Service de Santé des Armées» in Toulon. Following a presentation by Dr. Jean-Jacques RISSO of the research policy of the French Armed Forces Health Service and relationships with national and international research efforts, the committee listened to a presentation by Prof. Jacques ABRAINI and Dr. Jean-Eric BLATTEAU which was organised into three main parts: 1) Project birth and 2006-2010 general report (publications, financial and academic data, etc.) 2) Scientific report for 2006-2010: inert gas and oxygen pharmacology and therapeutics (Prof. ABRAINI); prevention and mechanisms of decompression sickness (Dr BLATTEAU).

3) Research unit project for 2012-2015. The presentation was comprehensive and detailed. Prof. ABRAINI explained that the organization of the research unit for the project would be different from what noted in the manuscript. He said that due to the lack of tenure-track position at the University of Caen, Dr Hélène DAVID who is a key scientist for the preclinical research of the project has moved to Quebec where she has got a tenuretrack position. Prof. ABRAINI, who has also obtained a renewable 3 years position of Adjunct Professor at Laval University (Quebec, Canada) as well as laboratory spaces, says therefore that the preclinical research of the project will not be performed in Caen but in Quebec in the Centre de Recherche, Université Laval Robert Giffard.

Therefore, the research unit will include three sites instead of two as thought initially. M. ABRAINI also clearly explained that establishing a joint research unit with CNRS and IRBA (UMR) to study the mechanisms of decompression sickness and discover innovative and efficient treatments requires establishing a "networkorganized research unit" since the number of scientists required for establishing a joint research unit cannot be reached in one single place. The presentation of M. ABRAINI and M. BLATTEAU were followed by lively and interesting scientific discussions and excellent answers to many questions.

Separate meetings then allowed free discussions with researchers with permanent position as well as with engineers and technician assistants. Due to major organisational changes (new laboratory spaces and research facilities at Laval University and IRBA) the research unit has no longer PhD students. The Committee had also an exchange with the representatives of CNRS and University to which the candidate unit wishes to be affiliated (surgeon-general Bigard from the French Armed Forces Health Services; Prof. BIOULAC from the CNRS; Prof. Denise by phone from University of Caen). Finally, the committee discussed with Prof. ABRAINI and Dr BLATTEAU: to clarify specifically the management of the research unit.

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

The project was initiated by research scientists from the University of Caen and the CNRS (Equipe de Recherche Technologique, ERTi 1083, UMR CNRS 6232) and the French Armed Forces Biomedical Research Institute (IRBA). The unit in Caen is devoted to preclinical studies on the neuroprotective properties of inert gases (IG) and oxygen (O2) for treating brain insults involving excitotoxic insults and the mechanisms by which these agents act. The unit in Toulon (IRBA and Hyperbaric medical centre) is devoted the studies of the physiopathology and treatment of hyperbaric disorders, particularly decompression Sickness, and neuroprotection of brain injuries. Both had common programs on the neuroprotective effects and mechanisms of action of Inert Gases (IG) and Oxygen (O2) for treating brain injuries.

On the basis of their successful collaboration and a mission letter of the director of the French Armed Forces Biomedical Research Institute (Institut de Recherches Biomédicales des Armées; IRBA), these research groups have decided to merge in a single research unit « Inhalothérapeutique des accidents de décompression », which will be organised between Caen, Toulon, and Laval University (Quebec, QC, Canada) where Dr Hélène David has moved. To avoid possible difficulties due to the "network" structure of the research unit and to the fact that he is only part-time in Caen, Prof. ABRAINI proposes to have a deputy director both in Caen (Dr Nathalie COLLOC'H) and in Toulon (Dr Jean-Eric BLATTEAU) in order to facilitate the day-to-day management of the research unit.

• Management team

The head of the joint research unit "inhalothérapeutique des accidents de decompression is Prof. Jacques H. ABRAINI. 2 Overall appreciation of the research unit

• Summary

The aim of the Research Unit « Inhalothérapeutique des accidents de décompression » is the development of innovative and efficient therapeutic strategies for treating acute decompression sickness whose symptoms are mainly neurological (90% of cases). State-of-the-art therapeutic treatments including recompression and hyperbaric oxygen thought to be the gold standard for treating decompression sickness are not satisfactory since 30% of patients show incomplete recovery with moderate to heavy permanent neurological disorders.

The research goal will be the understanding of the effects of IG and O2 as neuroprotectants for treating decompression sickness that is well known to result from the generation of gas bubbles in the tissues and the blood. Bubbles in tissues can provoke mechanical effects but the most important cause of decompression sickness is due to intravascular bubbles that induce ischemia directly or indirectly through platelet aggregation and alterations of the endothelium coagulation system.

The rationale for the research program is excellent since (i) IG and O2 have proven their preclinical efficiency for treating ischemic/hypoxic insults; (ii) decompression sickness mainly results from intravascular bubbles that produce ischaemia by obstructing vessels directly and producing platelet accumulation and alterations of the coagulation system.

• Strengths

The project is based on a mission letter of the director of IRBA, the French Armed Forces Biomedical Research Institute.

Staff members all have several years of research experience in IG and O2 pharmacology and/or hyperbaric physiology and medicine.

Staff members of the research unit yet have proven their ability to produce high quality research publications on inert gas pharmacology and neuroprotection within the top 15%, while being in different research units, thereby demonstrating their synergistic association and efficiency.

The yet demonstrated synergistic association and efficiency between staff members should allow excellent research progress.

The research unit yet has access to major research facilities that include medical imaging facilities at CYCERON in Caen, biophysics and X-ray crystallography facilities at ESRF in Grenoble, hyperbaric facilities for large animals at IRBA in Brétigny-sur-orge, and hyperbaric chambers for experimental and clinical studies at the French Navy Experimental Diving Unit and military hospital Ste Anne in Toulon.

Ability to rise funding from national and foreign partners and institutions: US Army Medical Research and Material Command, NNOXe Pharmaceuticals, Direction Générale de l'Armement

The research unit is characterized by deep and close collaborations between expert groups and scientists with complementary approaches from structural to preclinical gas pharmacology studies.

• Opportunities

The position of Prof. ABRAINI as adjunct professor and head of laboratory at Laval University in Quebec could allow establishing official partnership between the University of Caen and Laval University (Prof. Denise, Vice-President of the University of Caen has acknowledged that Prof. ABRAINI can make his research activity in Laval University provided that he comes for doing his teaching duties in Caen in a narrow period of time of 1-2 months).

The position of Prof. ABRAINI as adjunct professor and head of laboratory at Laval University in Quebec will allow establishing partnership between the IRBA and the US Navy as desirable by the head office of the French Armed Forces Health Services. M. ABRAINI will receive a medical corp US Navy biomedical scientist, Dr Denis COLOMB, for three years according to an exchange/training program between the US Navy and Canadian Armed Forces with the agreement of the French Armed Forces Health Services.

Being adjunct professor at Laval University and head of laboratory and with the US Navy, Prof. ABRAINI will have the benefit of applying for grants of US and Canadian offices such as the Office of Naval Research, NAVSEA, and DARPA (USA) and the Canadian Ministry of Defence.

International collaborations: Laval University (Quebec, Canada); US Navy Experimental Diving Unit (Panama City USA).

The CNRS could join the project of this joint research unit with the French Armed Forces Health Services depending on AERES report.

• Weaknesses

The major weakness could be the distance between the staff members of the research unit on three different sites and the fact that Prof. ABRAINI will be part-time in Caen and part-time in Quebec at Laval University and Dr. COLLO'CH will be often in ESRF Grenoble.

However, it is noteworthy that staff members of the research unit yet have been working together successfully while being members of different research units.

The journal median ranking where inert gases -oxygen pharmacology and neuroprotection data hav been published is within the top 15% (with a median impact factor of 5.4). However, despite the fact that decompression studies have been published in high standard specialized journals such as Journal of Applied Physiology; Undersea and Hyperbaric Medicine; etc., the research unit members still lack publications in top media such as Science, Nature, Lancet, etc.

• Threats

There is an important imbalance between the number of scientists with tenure position in Toulon (n=8) and that with tenure position in Caen (1 full time from the CNRS and 1 part-time from the university of Caen).

Depending on whether or not the CNRS will join the project, CNRS laboratory engineers and technicians (n=2) could not be available to be part of the project. Even if the CNRS joins the project, it should be noted that one laboratory engineer will retire next year.

Due to the distance between the sites that are part of the research unit, a scattering of research activities, coordination problems, and redundancies in research could be feared. However the goal of each research group is clearly defined while they are geared to perform complementary but different type of experiment. Furthermore, all committee members have agreed that international research collaboration is the right way to go nowadays. Large funding bodies, including the European Commission, are now more and more looking for considerable size international research project. Financial support seems secure from the French Armed Forces Health Services, and expected from the CNRS. The contribution of the University of Caen is still under discussion; decompression sickness is not a priority for that University.

• Recommendations

To avoid possible difficulties due to the organization of the research unit and to the fact that Prof. ABRAINI is part-time in Caen and part-time in Quebec, it is recommended as proposed by Prof. ABRAINI: * to delegate deputy directory to Dr. Collo'ch and Dr. BLATTEAU. * to strengthen the site of Caen, it is recommended (i) that the university of Caen should allocate to the project at least one tenure-track position for an academic researcher or at least research engineer in biophysics, (ii) that the CNRS should replace the laboratory engineer who will retire next year by a laboratory engineer with background in medical gas and hyperbaric research, particularly biophysics. * to avoid a scattering of research activities, it is recommended as proposed by Prof. ABRAINI to schedule three general laboratory meetings per year under the direct supervision of Prof. ABRAINI in addition to those that will be supervised by the deputy directors in Caen and/or Toulon. * to increase the research unit publication policy by enhancing the number of target journals from within top 15% to top 10%, including for studies on the mechanisms of decompression sickness.

• Production results 3 Specific comments

A1

• Appreciation on the results

Both research groups from Caen and Toulon have performed research that have led to new data and theories as regards to inert gas binding on proteins, inert gas pharmacology and neuroprotection (Caen) and the aetiology and mechanisms of decompression sickness and inert gas effects on neurotransmitters (Toulon). Collaboration between these two groups have led to publications in journals within the top 15% (FASEB Journal, Critical Care Medicine, Journal of Cerebral Blood Flow and Metabolism, PNAS, etc.).

• Major findings and discoveries during the past 5 years include:

Accessibility and hydrophobicity are the major criteria for IG binding in proteins' hydrophobic pockets as shown by structural biophysics and crystallography studies.

Xenon and nitrous oxide offer global neuroprotection by improving histologic and neurologic outcomes through blockade of NMDA receptors and excitotoxic processes in a rat model of mechanical acute stroke.

Xenon is a tPA inhibitor and as such inhibits tPA-induced thrombolysis and tPA-induced proteolytic adverse effects in a rat model of thrombo-embolic stroke. This indicates that xenon should be used to provide neuroprotection only once reperfusion has occurred.

Nitrous oxide is a tPA inhibitor and inhibits tPA-induced thrombolysis but favors tPA-induced adverse effects. This provides a definitive advantage to xenon compared to nitrous oxide.

Helium produces global neuroprotection by improving histologic and neurologic outcomes in a rat model of mechanical acute stroke due to its high specific heat that is 5-fold that of air. Combining xenon and helium could be beneficial since hypothermia has synergistic effect with xenon.

Intra-ischemic 100% normobaric oxygen (NBO) possesses in vivo thrombotic action by increasing tPA enzymatic activity. But, in contrast, post-ischemic NBO increases brain damage and swelling. This indicates that NBO should be used before but not after reperfusion.

Hyperbaric narcotic gases induce a decrease in the release of many neuromediators such as glutamate and dopamine. TREK-1 channels may play a role in inert gas action.

Aetiology, prevention and treatment of spinal cord decompression sickness: symptom latency after surfacing; time intervals between symptom onset and hyperbaric treatment.

Aetiology, prevention and treatment of spinal cord decompression sickness: role of right-to-left shunts (patent foramen ovale); preconditioning methods to decrease of bubble generation.

Aetiology, prevention and treatment of spinal cord decompression sickness: persistence or worsening symptoms after recompression; clinical and imaging (MRI) data.

Development of a clinically relevant model of decompression sickness in the rat: mechanisms of decompression sickness; endothelial immuno-inflamatory processes; platelet accumulation to the gas bubble surface; gas bubble-induced ischemia and thrombin production.

Development of a clinically relevant model of decompression sickness in the rat: preclinical studies with several compounds acting on platelets accumulation. Day-to-day management should be similar in the joint research unit project « Inhalothérapeutique des accidents de décompression », but scientific directory could be quite difficult since Prof. ABRAINI is part-time in Caen and part-time in Quebec City. Delegation to deputy directors as proposed by Prof ABRAINI will be appropriate to manage day-to-day the research unit programs. All members of the research unit board (Prof. ABRAINI, Drs BLATTEAU and COLLOC'H as deputy directors, and Dr RISSO as the representative of the director of IRBA) want to keep the way of passed functioning that has allowed producing high quality publications in combination with general laboratory meetings that will be held 2 times a year in Caen and Toulon, as well as in Quebec City (board members only).

• Appreciation on the scientific strategies and project

The translational research project « Inhalothérapeutique of Decompression Sickness » is largely relevant. The research project will focus mainly on the understanding of the effects of IG and O2 as neuroprotective agents for treating decompression sickness, which is well known to result from the generation of gas bubbles in the tissues and the blood.

The rationale for the research program is good since (i) IG and O2 have proven their preclinical efficiency for treating ischemic/hypoxic insults; (ii) decompression sickness is thought to result mainly from intravascular bubbles that produce ischaemia by obstructing vessels directly and through platelet and thrombin accumulation. Unpublished preliminary studies have proven that decompression sickness has an excitotoxic component.

The IG effects for treating decompression sickness yet has not been studied although positive results would constitute a decisive advance since (i) IG could have neuroprotective action without adverse effects; (ii) gold standard therapeutic strategies including recompression, hyperbaric oxygen, and drug treatments interacting with coagulation and inflammation have remained unsatisfactory because 30% of patients show incomplete recovery with moderate to heavy permanent neurological disorders.

The feasibility of this translational research project seems secure. Both similar basic and preclinical investigations have been performed previously with success by Prof. Abraini, Dr Colloc'h and Dr Risso. The mechanisms of neurological decompression sickness remains largely to be specified but preliminary experiments yet have proven the involvement of excitotoxic processes. Initiating clinical studies will depend on preclinical results, but could be performed since the staff members of the diving and hyperbaric medical unit of the military hospital Ste Anne are part of the project.

The rationale and steps of the research project are very clearly and logically stated from basic and preclinical studies to clinical trials based on the research unit's previous findings on the mechanisms of action, gas binding mode on proteins, mechanisms of decompression sickness, and neuroprotective and adverse effects of IG and O2 in a thrombo-embolic acute ischemic stroke model.

Main research goals are:

•

To study the binding of IG on enzymes relevant to ischemia and neuroprotection and to oxygen transporter proteins, gas-globin complexes such as myoglobin and neuroglobin.

•

To determine the possible and respective role and contribution of apoptosis and necrosis in neurological decompression sickness.

•

To determine the role of TREK-1 channels, which have been demonstrated to modulate IG effects, in neurological decompression sickness.

•

To perform preclinical studies to determine IG effects when given after hyperbaric oxygen, IG effects when given alone, IG effects when given after normobaric oxygen, IG effects when given alone or in combination with oxygen under hyperbaric conditions, as compared to hyperbaric oxygen that is thought gold standard treatment today.

•

To perform preclinical studies with combination of IG and/or O2 as above with others therapeutic strategies such as EPO.

•

Depending on preclinical findings, to perform human experimental studies and clinical trials. This could include: (i) experimental studies on safety and calculation of decompression procedure while breathing IG at hyperbaric pressure; (ii) clinical trials with IG alone, in combination or sequentially with oxygen for treating neurological decompression sickness as compared to state-of-the art gold standard practice with hyperbaric oxygen alone.

• Depending on the way IG will be used, this could be a hard step to perform as it could combine clinical practice, statistical trials, decompression safety, and technical aspects due to pressure. However hyperbaric clinicians from the diving and hyperbaric medical unit in military hospital Ste Anne are experts in the field.

Conclusion

The competency and experience of the research scientists involved in the project is widely and internationally recognized. Possible weakness due to the distance between the research unit sites should be resolved by the presence of deputy directors as proposed by the research unit director.

The number of publications and patents is at the top and even impressive for the field of inert gases and oxygen pharmacology and neuroprotection, and decompression sickness.

The Research in neuroprotection afforded by noble gases made by this laboratory is leading the field worldwide.

This project is a golden opportunity to become a leading figure in military and civilian diving research; the use of inert gases for treating the decompression sickness is innovative and promising pathway.

:

  Number of permanent researchers with teaching duties (recorded in N1) who are active in research 1 A2: Number of permanent researchers (CNRS, SSA-IRBA) without teaching duties (recorded in N2) who are active in research 8 A3: Ratio of members who are active in research among staff members [(A1 + A2)/(N1 + N2)] 90% A4: Number of HDR granted during the past 4 years 2 A5: Number of PhD granted during the past 4 years 8

Statistiques de notes globales par domaines scientifiques

  (État au 06/05/2011)

	Intitulé UR / équipe	C1	C2	C3	C4	Note globale
	INHALOPHARMACOLOGIE EXPERIMENTALE ET CLINIQUE	A	A	C	A	B
	C1 Qualité scientifique et production
	C2 Rayonnement et attractivité, intégration dans l'environnement
	C3 Gouvernance et vie du laboratoire
	C4 Stratégie et projet scientifique

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%
	*

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

• Appreciation on the impact, attractiveness of the research unit and quality of its links with international, national and local partner Development of a clinically relevant model of decompression sickness in the rat: preclinical studies preclinical studies with several compounds acting on platelets accumulation.

Research unit members had attracted external funds from the Direction Générale de l'Armement, the NNOXe Pharmaceuticals, the US Army Medical Research and Materiel Command, etc.

Research data leading to 5 patents and patent applications.

Research projects included international collaborations with the US Army Medical Research and Materiel Command; the University La Sapienza (Roma); NNOXe Pharmaceuticals, and foreign hyperbaric medical centres.

Research unit members are well-recognized scientists in the field of inert gas pharmacology and/or hyperbaric medicine and physiology. This includes:

•

Choice of Prof. ABRAINI for mentorship of Dr Colomb by the US Navy medical corp.

• 19 invited lectures and conferences;

• 11 awards and prizes, both national and international (Soriano prize of the French national academy of medicine; Zetterström memorial medal of the Swedish defence research centre; Zetterström award of the European Baromedical Society; Silver medal for scientific work of the French Armed Forces Health Services, etc.);

•

Membership of editorial boards in medical gas, anaesthesiology, and pharmacology journals.

• Participation to international or national scientific survey networks: Divers Alert Network, European Committee for Hyperbaric Medicine; North Atlantic Treaty Organisation.

• Appreciation of the management and life of the research unit Research scientists, technicians and past PhD students have had the opportunity to participate to national and/or international scientific meetings.

Research scientists are involved in teaching activities in master and doctoral curricula in Caen, Marseille, Lyon, and Toulon, as well as in continuous education programs and civil and defence postgraduate programs.

All staff members, including researchers, technicians, and past students, have benefited training sessions on the use of medical gases.

Technicians have had the opportunity to sign scientific papers.


Fabrice Mr

Jardin

Eric Mr

Delabesse

Jose A Mr

Martinez-Climent

Mauro Mr

Delorenzi

Serge Mr

Romana

Ms Florence

Jean Mr

Rosenbaum

Mr Cafer Oskul

Pierre Mr

Centre Henri Vera

Becquerel

The visit took place in Rouen on November 25, 2010 in the comprehensive cancer center building, Centre Henri Becquerel. The site visit began at 8:45 am with a meeting of the committee with the AERES representative.

At 9h15 am, the group leader first briefly introduced the general strategy of the lab. This was followed by 3 short presentations by several scientists from the team until 11h15 am. The committee then split into 3 subgroups in order to meet separately the PhD students, the technicians, and the scientists. The committee then met University, INSERM and other local representatives during 30 minutes. At 1:30 pm, the committee met for debriefing and drafting the report. The visit ended at 3:30 pm.

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

The INSERM unit U918 has been created in 2008 and directed by Hervé Tilly. The unit is located in the medical area of Rouen, inside the Centre de Lutte contre le Cancer of Rouen (centre Henri-Becquerel), next to the CHU of Rouen. The surface of the lab is 382 m2. The focus of the group is to identify and characterize recurrent genetic abnormalities in lymphomas.

 Management team

The unit is currently directed by Mr Hervé Tilly and assisted by Mr. Fabrice Jardin, Mr. Christian Bastard and Mr Philippe Ruminy. The direction will move to Mr. Fabrice Jardin due to the retirement of Hervé Tilly. Good scientific production coming from a small team specialized in deciphering the genetic abnormalities of diffuse large B-cell (DLCBCL) and follicular (FL) lymphomas with relevance to the clinical practice.

 Staff members

 Strengths and opportunities

 Recommendations

We recommand to focus on the leading diseases investigated by the team (DLBCL, FL) and on the mechanistic consequences of mutations unraveled by them (functional studies, molecular therapeutics, etc). By this way, the team should be able to attract PhD students and post-doctoral fellows. The team is a leader in France in the molecular characterization of lymphoma oncogenes. The scientific production of the team is very solid. Overall, the publishing scientific contribution of the group during the last four years was 17 papers (with 69 additional papers published within clinical and biological networks).

The papers have been published in top journals of the specialty : 2 Blood, 8 Leukemia and 1 Oncogene papers among the 17 published as first and/or last author by a team member.

Among the additional 69 papers, top rank journals were also present such as J Clin Oncol, Blood and J Exp Med. The team is regularly presenting their results to the American Society of Hematology annual meetings. Only one PhD thesis was presented during the last 4 years, but five PhD students are currently in training.

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

Since the cloning and identification of the BCL6 oncogene in 1993 by the team, they established strong collaborative studies between genetics and clinics either in the clinical center Henri-Becquerel or inside the GELA (Groupe d'Etude des Lymphomes de l'adulte) network, a leader in the treatment of these diseases. The team was able to participate in and for some of them to coordinate large national networks, getting a share of these competitive fundings (such as INCa). However, the team recognizes its difficulties to attract students and scientists to their labs. A post-doc student just arrived. The leaders of the team participate to international meetings such as ASH (6 oral communications as first author from 2006 to 2010). The former leader was regularly invited to give talks. The team has good national visible collaborations, but the international collaborations have not been very active during the last four years.

 Appreciation on the management and life of the research unit

The new director is efficiently leading his team. Regular meetings are scheduled every two weeks (bibliography reviews and progress of the projects). The team seems to benefit from a good collaborative attitude of all members. Some people of the lab are teaching either in the Faculty of Medicine or at the Ecole Doctorale of Rouen.

 Appreciation on the scientific strategy and the project

The projects are mainly focused on translational research, combining a unique collection of samples and clinical annotations with the genetic data identified through diverse technological approaches. The scientific project is dedicated to diffuse large B cell lymphoma (DLBCL) and follicular lymphomas (FL) oncogenes, centered on the characterization of the genomic abnormalities of the B-cell receptor genes. This is a promising project, original, feasible and clinically relevant. This team reported an exciting observation of the IgM expression at the cell surface in activated B-cell (ABC) subtype of DLBCL (ABC-DLBCL). The detection of IgM expression might become a strong diagnostic marker for ABC-DLBCL and subsequently may represent a predictive marker of response to therapies inhibiting the NF-kB pathway. The other projects regarding these diseases are mainly collaborative studies and could be fruitful in the future for new developments of the lab and for maintaining collaborative integration with other French groups. Beside DLBCL and FL, two projects are aiming to investigate specific genetic abnormalities in very rare diseases.

It seems important that the lab develops either by itself or in collaboration with other groups functional studies to decipher the basis of the genomic abnormalities detected in their translational studies and their physiological relevance to the disease.



  Date and execution of the visit



  Expertise of genetic abormalities  Large collection of lymphoma annotated samples  Strong collaboration between clinicians, cytogeneticists and pathologists  Good position in national networks  Weaknesses and threats  Lack of functional studies to validate the results regarding the genetic abnormalities identified by the group  Few scientific students  Small team  Only one full time scientist



  Production results A1: Number of permanent researchers with teaching duties (recorded in N1) who are active in research 2 A2: Number of permanent researchers without teaching duties (recorded in N2) who are active in research 2 A3: Ratio of members who are active in research among staff members [(A1 + A2)/(N1 + N2)] 100% A4: Number of HDR granted during the past 4 years 1 A5: Number of PhD granted during the past 4 years 1 3  Specific comments  Appreciation on the results

Sciences du Vivant et Environnement

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

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