Jean-Pierre Vannier

PRATS M Hervé

Ms Dominique

Jean Rosenbaum

The visit took place on November 24 at the Rouen University, campus of Medicine and Pharmacy. The first part, devoted to a general presentation of the past and the general orientation of the proposed new organization, was given by the director who is also the proposed future director. After that, two young researchers gave a 30 minutes presentations each (including discussion) that represented the two main scientific fields developed in the project. The committee then split to meet with the students and post-docs, the scientists and the technicians of the lab. After that, the committee reconvened to meet the University representatives. Finally, the committee met in private to discuss and to prepare this report.

Overall, the evaluation was well prepared and organized and the execution of the visit went smoothly.

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

The location of the Unit is split between two campus of the Rouen University: Faculty of Medicine and pharmacy, close to the hospital, and Faculty of Sciences, at Mont-Saint-Aignan where is the sub-group in charge of SIMS (Secondary Ion Mass Spectrometry) technology. It should be noted that the University is committed to aligning skills and in particular to promote a new home for the SIMS in the proximity of the Faculty of Medicine.

Over the past ten years, this team has been formed by aggregating, around several axes, professors and assistant-professors from different disciplines. Through the efforts of the Director, the trend was taken for restricting the topics around two axes i.e. development of biological applications of the SIMS technology and tumor angiogenesis/ development of synthetic extracellular matrixes. He also tried to promote a better targeting of themes consistent with the regional science policy and succeeded in creating a spin-off company.

 Management team

Management is mostly assumed by the Director but management of external funds were fully under the responsibility of each principal contractor. Furthermore, decisions that implicate most of the team (equipments, new PhD students, etc.) were taken by all the staff. The team consists of 17 permanent members, 12 from University and 5 clinicians. The origin of the permanent members is varied and complementary: physicists/chemists, biologists or clinicians. 9 PhD students and 2 post-doc are also currently working in this group and are distributed among the differents topics. The output of the current group should be regarded as reasonable to good for a group composed by staff members more or less overloaded with teaching duties. They have established interesting collaborations with leaders in the field of SIMS technology (european ENLAB program) and also with a group in Shanghai (University of Fudan). One weakness of this group is that the diversity of topics is still too large despite the efforts to promote more overlaps.

 Staff members

Even if the research unit is split into two different sites in Rouen, a major effort is made to homogenize the different themes developed since several years i.e. improvement of the biological applications of the SIMS technology and differents aspects of tumoral angiogenesis.

 Strenghts and opportunities

The group has developed strong links with clinical research (5 hospital practitioners have joined the group) which is a promising opening that should be strengthened. Also it must be noted the high quality of PhD students involved in the different topics.

The very good activity in transfer to industrial applications allows the group to obtain external grants but also to participate very actively in the creation of start-ups that is also a putative pool of jobs for students trained in the team.

An additional strength lies in the fact that within a European network focused on technology SIMS the group is responsible for developing the biological aspects of these methods.

The group also benefits from a strong support from the University that participates actively in solving problems such as streamlining the operation and maintenance of the SIMS apparatus, etc.. One major strength of this research unit lies in its ability to transfer their different findings to the economical field and to obtain interesting fundings for this goal. Integration to the local policy (University and Region) is very satisfactory. Furthermore, the director and some permanent researchers have a good national and international visibility. Finally, this team is attractive for young researchers as shown by the number of the current PhD students and those that have been granted during the past 4 years.

 Weaknesses and threats

Too many projects are mainly descriptive. Mechanistic aspects should be developped to publish in journals of higher IF.

The lack of full time researchers is detrimental to greater efficiency.

Although visibility is quite good, it remains limited by the diversity of topics.

In addition, the scientific animation should be improved.

 Recommendations

The threat for the group is that of dispersing the efforts over too many different experimental systems that might diminish the productivity. At the same time working in different systems can also be considered as an opportunity. Although it is clear that the organization of the group goes in the direction of greater integration of different subjects, it is necessary to continue and expand this effort.

It seems necessary to increase the frequency of internal scientific meetings and to encourage the participation of staff members to supervise the master and PhD students more regularly and more efficiently. Two main axes have been presented. The first one is dedicated to the identification of new targets in the field of tumor microenvironment and angiogenesis for therapeutic application. Despite the high competivity of these themes, the group contributed to demonstrate the implication of several candidates or pathways including tetraspanins, small GTPases, CXC chemokines on cell migration, proliferation and angiogenesis. The impact of the research results is mainly descriptive and applied to therapeutic objectives.

The second axis is much more technological and is dedicated to the improvement of the applications of SIMS (Microscopy/mass spec imaging) to biological problems as different as proteomics of small samples or DNA combing. The originality and quality of these results is reflected by the obtention of public grants but also financial support of OSEO to promote the creation of a spin-off biotech. Most of these publications are in good journals of speciality. 9 thesis were produced during this period and the average of publications by student is ≥2.

Several partnerships have been developed. A strong collallaboration with Pr Migeon's lab in Luxembourg gave rise to an Europeean grant in which the Rouen's laboratory is in charge of the biological development of some aspects of the SIMS technology. A long term partnership is also developped with a Chinese institute in Shangaï.

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

One member of the team recently won the Annabelle Merieau of Elie Wollman Prize 2009 and is a member of the « Faculty of a 1000 ». Two other members obtained OSEO Awards. 3 members of the team are « professeurs émérites ». Locally, the team is partner of "Cosmetic Valley", a "pôle de compétitivité".

Participation to international conferences is very satisfactory and the team director is regularly invited to international meetings in France and abroad.

These last four years, the team has recruited 3 young researchers, 2 as assistant professors (maître de conférences) and 1 professor. All of them are from France but only one did his thesis in Rouen. It is evident that these recruitments dynamised the group, espacially in the the field of the SIMS technology. The team is locally attractive for young scientists as 9 PhD students have been trained within 4 years, most of them being then employed by industry rather than following academic carriers.

The research and the objectives of the group make this team competitive in raising external fundings, especially in the field of technology development that is their major source of fundings. At present, an ANR program is close to finish but another one is now accepted. This last one concerns the applications of artificial matrix based on reticulated hyaluronic acid with extra-cellular matrix molecules. Furthermore, an European funding is still operative.

The team participates in a European network on the theme of development of SIMS technology applications in the field of new approaches in proteomics and genomics. Furthermore, the collaboration with a team of Shanghai in the field of tumor angiogenesis is still active.

The committee underlined the very good capacity of the team to transfer their compentences to industry since one spin-off company has been created in recent years and another project, funded by ANR as mentionned above, is planned for the next year. The group is also very active in valorization through good IP management.

 Appreciation on the management and life of the research unit

The group has ben trying to optimize the organization despite the fact that the team is located on two different sites in Rouen. However, there is obviously a very good working atmosphere, models and tools are easily shared. Also note that most of the technicians are involved in common tasks or are shared between different groups.

Scientific animation : a scientific meeting is organized every other week and a conference every month.

There is a strong commitment to teaching of all the staff at all academic levels. Furthermore, most of them have teaching responsabilities in pharmacy, medicine or live sciences faculties and are also implicated in University councils.

The team was a partner of an IFR and even though this kind of structure is not renewed, several efficient technical and scientific exchanges still persist with surrounding research units.

 Appreciation on the scientific strategy and the project

The projects developed by this group are interesting, relevant from the standpoint of health research and reasonable as to their objectives. However, despite obvious efforts, too many different sub-projects still coexist. An effort to better focus the main fields of interest of the group should be actively pursued.

Innovative projects with risk-taking were established, mainly in the fields of technological applications i.e. biological and biochemical applications of the SIMS technology and development of the use of artificial matrices for stem cells cultures.

The resources are well managed. Fundings come from the University, ANR, industry and, in the field of cancer, from Ligue Régionale and other associations, mostly local. However, a small percentage of all grants should be shared for purchasing new equipments of general interest for the lab members.



  Date and execution of the visit

  The group should try to attract young leaders capable of applying to EPST positions.It is also important that the group increases its participation in the local scientific environment to improve the quality of scientific output.  Production results A1: Number of permanent researchers with teaching duties (recorded in N1) who are active in research 9 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)] 9/11 A4: Number of HDR granted during the past 4 years 3 A5: Number of PhD granted during the past 4 years 9 3  Specific comments  Appreciation on the results

  Among the 140 publications published these 4 last years : -70 are signed as first or senior author by members of the team -20 have an IF >5 including HUM MOL GENET (7.4) 2005 and 2006, STEM CELLS (7.7) 2006 and a remarkable review in ANNUAL REVIEW OF MICROBIOLOGY, etc.

Sciences du Vivant et Environnement

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

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

Réf : S2UR120001257-Microenvironnement et renouvellement cellulaire intégré -MERCI-0761904G

Monsieur le Directeur, Je vous prie de bien vouloir trouver ci-joint la réponse formulée par la direction de l'équipe d'accueil MERCI au rapport du comité de visite.

Je voudrais tout d'abord souligner le bon déroulement de la visite du comité d'évaluation et la qualité des échanges.

Je précise que si l'IFRMP 23 ne sera pas reconduit en tant qu'IFR, comme le note le comité de visite, il sera cependant remplacé par une SFR intitulée Institut de Recherche et d'Innovation Bio-médicales de Haute Normandie (IRIB-HN). L'EA MERCI, qui dispose déjà des équipements de pointe, accèdera aux services communs et plate-formes techniques (2 IbiSA) de cette nouvelle SFR.

Je souligne aussi l'apport de deux professeurs émérites encore très actifs en recherche qui n'émargent pas dans les tableaux des effectifs de l'Unité. J'ajoute que l'Université a toutes les raisons d'être satisfaite des EC récemment recrutés qui ont montré, au cours de la visite du comité, leur capacité à prendre la relève. L'Etablissement soutient et accompagne donc cette EA qui est très impliquée dans une recherche translationnelle et dans l'innovation technologique avec des collaborations internationales.

Je vous prie de recevoir, Monsieur le Directeur, l'assurance de ma considération distinguée. Parmi les modèles développés au sein du groupe, certains sont originaux mettant en valeur les compétences et le savoir-faire de collègues et d'équipes partenaires de la f'aculté des Sciences. Comme gela a été souligné dans le rapport, ces modélei sont porteurs de valorisations scientifiques et industrielles. Ils peuvent constituer les bases de ..grorpË-.nts plus larges avec d,autres équipes intéressées par les biomatériaux. L'imagerie SIMS en Uioiogie, est une spécificité de l,équipe. Elle a suscité de la part de notre groupe la mise en place de collaboiations majeuies ouvertes à l,international. Nous nous engageons à développer davantagè ces collaborations. Les aitres techniques et modèles sont actuellement accessibles au sein de I'IFR 23 puis le seront au sein de ce qui sera très vraisemblablement la fédération de recherche, à la création de laquelle nous participons.

Dans le passé récent, le management du groupe a été fondé sur une organisation tacite mettant en valeur une coresponsabilité entre les quatre animaieurs des axes (cf précéàent quadriennal). Trois à quatre fois par an, un Conseil de Laboratoire (avec des membres "de droit,, et des membres élus (étudiants) permettait de fixer les orientations et de décider des investissements lourds. Les délibérations étaient l'objet d'un compte rendu. En cas de besoin, le remplacement du directeur de laboratoire était assuré pour toutes les opérations techniques par l'un des aniÂateurs d'axes. La mise en place au sein de notre Université d'une réflexion sur le management des équipes a été très appréciée au sein du groupe qui s'est engagé a revoir son fonctionnement traditionnél àt de suivre dË'façon assez formelle les recommandations qui ont été proposées à la communauté scientifique par notre Université. Dès que la labellisation de notre groupe, nous sera notifiée, des élections seront organisées pour permettre d'attribuer les rôles et responsabilités.

I 'e groupe de recherche s'est constitué par le passé, autour d'une réflexion commune afin de mettre en évidence des mécanismes biologiques communs à différents modèles. Notre objectif a alors été d'explorer les apports possibles de iertaines techniques innovantes. Actuellement nous pouvons aller plus loin et associer aux démarches expérimentàles en cours, une recherche plus fondamentale soucieuse de modéliser les mécanismes intégratifs à la base du fonctionnement cellulaire dans son microenvironnement. Cet objectif a été bien compris et a fait I'objet de plusieurs discussions destinées à meffre en place un tel projet et ce, en lien avec le projet Epigenomique du Genopole@ d,Evry avec lequel nous collaborons déjà. L'intérêt est, outre d'améliorer I'impact deJ publicationJ des cherchelrs, de mettre en place un pôle de réflexion sur cette vision intégrée des mécanismes biologiques.

Concrètement il est envisagé d'orienter notre recrutement futur vers des chercheurs (eunes cheicheurs universitaires, post-doc, ...) en mesure de consolider cette orientation. A court terme, afin dynamiser [animation scientifique dans ce sens, des réunions thématiques vont être organisées entre les différents acteurs du groupe.

La formation des jeunes chercheurs en particulier des étudiants en thèse avait justifié la mise en place de séances de bibliographie avec ou sans exposé des travaux en cours. Après une interruption de quelques mois, l'été dernier, ces séances ont repris. Elle se font sous la direôtion du profesjeur Vic Norris, en anglais en suivant en cela les recommandations du groupe d'expert de I'AERES. Les chercheurs séniors sont conviés à ces rencontres et leur participationist quasi syitématique lorsque sont évoqués les travaux en cours. Un 2è'" ffpe de rencontre a été récem-.rrt *i, Ln place pour les jeunes collègues, à I'interface entre recherche expérimentale et recherche clinique. Chaque semaine ur.;.rn. collaborateur (interne, CCA ou étudiant en thèse) présente une publicâtion susôeptible de nourrir la réfl exion clinique et scientifique.

La croissance du groupe de recherche a étéjusqu'à présent, assurée par des adhésions successives de collègues enseignant-chercheurs ou professionnels ayant une activité de recherche (ex. pH) intéressés par les thématiques abordées. L'accueil de chercheurs temps plein est souhaité et un travail de prospection va être entrepris.

En ce qui concerne le financement de nouveau équipements, le groupe n'avait pas I'habitude de prélever un pourcentage sur les crédits de fonctionnement acquis par tes portàurs de p.ô3.t. L'Université assure en partie cette fonction au travers du BQR auquel participe le groupe comme ,toiisant" et comme demandeur. Mais en revanche, I'ensemble du groupe s'est môbilise et va le faire encore cette année autour d'opérations dédiées à I'acquisition d'un équipement majeur (microcinéma, équipement protéomique, PCR qualitative). Cette mobilisation se fait en partenariat avec des club-service.

Cependant la remarque du groupe d'expert a été entendue, et ce d'autant plus, que la prise en charge de réparation urgente d'un matériel lourd a déjà eté faite selon cette procédurô.

Professeur JP Vannier. le 13 avril 2011


M Jacques-Olivier

Claude-Agnès Mrs

Reynaud

M Ralf Kuppers

M Olivier Thaunat

Marie-Christine Mrs

Bene

M David

M Pascal Gente

The visit took place on January 25th, and included a three-hour presentation of past achievements presented by the former director of EA2216, followed by future projects presented by the new director and by senior scientists from the group, with each topic submitted to scientific discussion with the members of the committe. Meeting with scientists (in the absence of both the future and former directors), with the technician and with students took place before a short break devoted to discussions in front of the posters presented by the PhD students. A presentation of the local university environment was presented by university representatives (university, CHU, and Ecole doctorale).

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

The group was created in 1983 by P. YOUINOU, and, after being reconducted under various denominations as a research unit supported by the ministry of research, became EA2216 in 1992. P. YOUINOU will retire at the end of the year, and the direction will be assumed by J.O. PERS. The unit is located next to the laboratory of immunology of the Brest University Hospital (Morvan) and has developped strong links with the surrounding clinical departments of rheumatology, hematology and nephrology.

The team has developed a long-standing expertise in the field of auto-immune diseases (Sjögren syndrome, systemic lupus erythomatosus and rheumatoid arthritis), with a specific emphasis of the B-cell effector part, expertise that is translated into a considerable activity in the field of therapeutic trials, while also developing studies on normal B cell physiology. A special focus over the years has been devoted to the specific subset of CD5+ B-cells.

 Management team

As mentioned above, the direction of the team will change at the end of the year, a transmission that has been carefully anticipated and prepared, and appears to meet the consensual approval of all members of the team.

 Staff members

The structure of the team has the specific features of an Equipe d'Accueil within a University hospital, being composed of permanent members with major clinical and/or teaching duties, with no full-time scientists or post-docs.

All scientists (including an engineer) have an HDR, allowing the mentoring of a large number of PhD students, who are in charge of experimental projects. 2  Overall appreciation on the research unit

 Summary

The team has developed a specific expertise in the identification of the role of the B cell compartment in autoimmune diseases, and in particular in Sjögren syndrome, shifting the focus towards the involvement of B-cells, besides T-cells, in the pathophysiology of the disease. Specific questions have been developed concerning the role of the BAFF survival factor in auto-immunity, of the modulation of CD5 expression according to epigenetic disregulation in Sjögren syndrome and LED. More clinically focused studies have ben designed to decipher the mechanism of action of IVIg or anti-CD20 therapies. Several of these observations appears to lead to new developments concerning the regulation of the normal B cell compartment.

This group with a long history of prominence in the landscape of Health Science in Britanny is faced with the challenge of a transition from a charismatic leadership to a new management. This has been well prepared, and all senior researchers, although none of them is full-time scientist, manage to devote a significant portion of their time to research and are assisted by a skilled and motivated group of PhD students with good coordination. Based on both fundamental and clinically-oriented research, the group's fields of interest are centered on B-cell functions but should still strenghten their focus on the most promising axes.

 Strengths and opportunities

Among the specific strengths of the team are the strong links established over the years with the surrounding clinical departments. They allow very efficient translational research as assessed by the numerous clinical trials and cohort studies coordinated by the team. Its deep implication in the regional teaching environment, together with strong supports from Region Ouest and from the University and University Hospital has allowed for the establishment of a consequent task force of PhD students. The group is well-structured in spite of the lack of full-time researchers. A strong international network has also been developed by the former director, which will provide good opportunities for further cooperations and possibly post-Docs. Several very promising scientific projects rely on observations originating from the team, emphasizing the fruitful exchange between basic science and observations emanating from the study of auto-immune diseases. The next step, already quite advanced for some topics (CD5, BAFF), will obviously be to raise these observations to the level of concepts of general biological relevance.

The team will have a new director for the next 5-year term, after a previous directorship of 27 years. This transition has been carefully prepared, and the authority of the new head of the lab appears already well established and recognized. The new addition, in the team, of university-hospital professors in Nephrology and Rheumatology will strengthen the clinical input of the group's work.

 Weaknesses and threats

The new head of the lab will have to establish himself as a internationally recognized leader in the field in continuation with what was achieved by the former director. Whereas this could temporarily reduce the visibility of the group, the impact will obviously depend upon the quality of the science achieved, allowing the emergence of a new scientific leadership. Moreover, in the present organization of the team, the development of scientific projects relies on the sustained capacity of the group to attract and fund PhD students. Similarly, whereas the general funding level appears adequate, most of the grants obtained are modest, precluding the recruitment of post-doctoral fellows, and have to be regularly renewed.

 Recommandations

As the team lack full-time scientists, the variety of projects developed may lead to some dispersal, in particular considering topics for which strong international competition exist (e.g. the B regs topic) or for which high technology (involving high costs) may be required (e.g. epigenetics). A prioritization of the topics will be required to allow the team to make important and original scientific contributions.

 Production results

The team has an extensive publication record for the 5-year period of 2006-2010 (188 including collaborative works); however, many of these publications are editorials, comments or reviews. Among original research papers in which the team is leader (30 in total), 22 were published in journals with an impact factor >6 (Arthr. Rheum (10), J. Autoimmun (5), J. Immunol (5), FASEB J (1), Cancer Res (1)) and one paper in Blood (IF 10.5). A trend for a progressive increase in the impact factor of the publications can be noted over the last 5 years. 3  Specific comments

 Appreciation on the results

The team has a regular scientific output, published in good journals of general immunology (JI) or more specialized in auto-immunity (Arth. Rheum, J. Autoimmun). As a result, the team is internationally recognized in the field of clinical immunology. Among their contributions are studies establishing the importance of the B cell compartment in Sjögren' syndrome, including in the production of the BAFF B-cell survival factor; other contributions concern the editing process in peripheral lymphoid organs, its association with CD5 expression, and its abnormal persistence in autoimmune diseases (Lupus or RA). Finally, a large part of the scientific activity is devoted to the evaluation of therapeutic strategies (Rituximab, IVIg), with an original observation of a direct, non FcgRIIB-mediated, impact of IVIg on B cell signalization through the CD22 receptor. Finally, the team also has a very important clinical activity, being involved in clinical trials, including the coordination of the TEARS cohort, aimed at evaluating the efficacy of Rituximab treatment in Sjögren syndrome performed in 13 different centers.

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

The team has a major regional role in the mentoring of PhD students and appears able to attract, not only students from Brittany universities, but also from abroad (Turkey, Tunisia, Columbia, India), a possibility generated by its strong implication and recognition in international networks in the auto-immune field. The quality of mentoring is attested by awards attributed to PhDs. The team has also developed very good interactions with regional industrial partners, allowing them to collect resources from the professional tax.

This excellent visibility in the auto-immune field, together with this strong industrial partnership with local industries, allowed the organization in 2009 in Brest of the 10th International Symposium on Sjögren' syndrome (the previous one took place in Washington DC and the next one will be in Athens). If this international visibility in the field of autoimmunity is attested by the numerous invitations to international conferences, one should however mention that most of them concerned the previous head of the lab.

A major step forward in the scientific development of the team would be the possibility to recruit post-doctoral scientists, a strategy so far prevented by the lack of adequate funding support. Such a development would be required to achieve the recognition by French research agencies hoped for by the group.

 Appreciation on the management and life of the research unit

Within the specific structure of this team that includes mainly permanent scientists with major teaching and/or clinical duties and PhD students in charge of the realization of the projects, a specific attention is brought to regular and well-structured scientific animation and tutoring, including various types of meetings and exchanges implying also, for some of them, the clinical departments.

 Appreciation on the scientific strategy and the project

Several projects have been exposed during the visit, many in the continuity of previous works from the team. The study of a new variant of the BAFF survival factor appears very original and could be of wide relevance; this study is also developed in collaboration with a leading Australian scientist in the field. A very ambitious approach is also engaged in the study of CD5 expression, aiming at characterizing the function of demethylation (and more globally "epigenetics") as a potential deregulation target in auto-immunity. The impact of the B cell compartment in autoimmune diseases will be addressed through their effector function -a new and fast expanding domain-, and more specifically of their possible regulatory role. Immunotherapy by new anti-CD20 antibodies will be studied according to a new angle (the membrane environment of the CD20 molecule), and for IVIg, the role of additional targets at the Bcell surface will be addressed.

The recruitment of a PU-PH with an established expertise in the field of renal transplantation will allow the team to apply its expertise in a new topic, i.e. the role of B cells in the pathogenesis of chronic graft rejection. Valorization through the development of bi-functional antibodies will also be pursued.

The development of animal models is also planned, including a human CD20 transgenic mouse model that will allow the development of graft versus host disease.

In spite of the general focus on B cells common to all these questions, which is the hallmark of this group, the committee felt that the large number of approaches developed would require to be strictly prioritized, in order to mobilize efficiently the resources of the team to the most promising projects.



  Date and execution of the visit

A1:

  Number of permanent researchers with teaching duties (recorded in N1) who are active in research 8 A2: Number of permanent researchers without teaching duties (recorded in N2) who are active in research 3 A3: Ratio of members who are active in research among staff members [(A1 + A2)/(N1 + N2)] 8/8 A4: Number of HDR granted during the past 4 years 4 A5: Number of PhD granted during the past 4 years 7

Sciences du Vivant et Environnement

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

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

We thank the experts for their thoughtfui suggestions. We are pleased that they liked our proposai, so that their report is encouraging. This combines a view of the current situation and a summary of the future challenges. Our response is thus restricted to comment some of their recommendations.

1-Quite rightiy, their analysis points out that the succession of the former director has long and carefully been prepared. That is, the new director knows the challenges he has to face, and the responsibilities he has to take on, v/z scientific récognition but aiso the strong links of the lab with the clinical departments, and the inclusion within an international network.

2-As kindiy deplored by the experts, the lack of full-time researchers is a catch-22 problem. Such a scientist is recruited by a team, provided it has been acknowledged by the INSERM, and the other way round, the group is acknowledged, provided it includes full-time researchers. Ours is composed of members with clinical and/or teaching duties. As a matter of fact, the situation would be (will be?) greatly improved following récognition of the team by French research agencies. This constitutes our major objective over the forthcoming contract.

With this in mind, two post-doc researchers will be recruited in September 2011.

3-To prioritize research projects in order to effectively assign the bulk of our resources to the most promising projects has aiready been initiated. For example, studies on antiendothelial cell antibody and GvH have been given up, to strengthen our visibility in the autoimmune field. This is now restricted to compétitive topics, such as "B regs, BAFF and CD5".

In conclusion, we are fully awàre that our forthcoming task is to take thèse challenges.

Needtess to say that the expertsj^vices will be followed to the letter.

Youfnou Jacques-Olivier Pers

Téléphone : (33) 2.98.22.33.84 -Telet"axT(^ E-mail : pers@umv-brest.fr