president Michel Cosnard

Ralf Ludwig

come

IRMAIC -Immuno-régulation et remodelage tissulaire dans le cancer et dans les maladies auto-immunes et inflammatoires

Evaluation report

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

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

Unit name:

Immune With the contractualization procedure framework of the units of research for the next contract 2018-22, the 2 research units EA 7319 "Immunodermatologie, cytokines and cancer", created in 2014, and EA 4683 "IMAB" decided to merge around a common scientific project. The new unit Immune dysregulation and tissue remodelling in cancer, autoimmune and inflammatory diseases will be located at the "Université de Reims Champagne-Ardenne" (URCA).

Management team

The designated director of the unit is Mr Frank ANTONICELLI.

HCERES nomenclature SVE1LS6, SVE1LS7, SVE1LS4.

Scientific domains

All groups have a strong translational focus and aim at identifying biomarkers of autoimmune, inflammatory diseases and cancer. The ultimate aim of biomarker identification is the development of innovative therapeutic approaches. The unit "Immuno-Regulation dans les Maladies Autoimmunes, Inflammatoires et dans le Cancer" aims to unravel biomarkers of inflammatory diseases and cancer to translate these insights into pathogenesis in innovative treatment approaches. To achieve this goal, the unit is composed of 3 groups: the "Immuno-régulation cutanée" group, the "Immuno-régulation pulmonaire" group and "Immuno-régulation et cancer" group.

Unit workforce

Unit workforce

In the last years, the number of publications increased, and the scientific quality and output of the last period was excellent.

The unit vividly interacted with the social, economic and cultural environment. This is reflected by patents, strong interactions with hospitals, and with several start-up companies, aiming at translating research findings into clinical use.

Given its size the unit also performed excellent regarding the training through research.

The strategy for the next 5 years is clearly stated. The excellence in skin autoimmunity, where the unit is one of the leading institutes worldwide, will support the dynamic in the field of lung inflammatory diseases, especially Chronic Obstructive Pulmonary Disease (COPD), where the unit has already an excellent expertise.

Collectively, the unit was successful during the last period, has re-focused its scientific program and now is expected to have a significant impact in the fields of autoimmunity, chronic inflammation and cancer. The highly interdisciplinary and translational nature of the unit will ensure translation into clinical application.

2

  spent at least 12 months in the unit Number of Research Supervisor Qualifications (HDR) obtained during the period 0 Assessment of the unit Global assessment of the unit

  dysregulation and tissue remodeling in cancer, autoimmune and inflammatory diseases

	Unit acronym:	IRMAIC
	Label requested:	EA (merge of two research units EA 7319 and EA 4683)
	Current number:	EA 7319
	Name of Director (2016-2017):	Mr Frank ANTONICELLI
	Name of Project Leader (2018-2022):	Mr Frank ANTONICELLI
	Expert committee members
	Chair:	Mr Ralf LUDWIG, University of Lübeck, Germany
	Experts:	MS MURIEL ANDRIEU, Institut Cochin, Paris, (representative of supporting
		personnel)
		Mr SELIM ARACTINGUI, Hospital Cochin, Paris
		Ms Pascale COHEN, Université de Lyon 1 (representative of the CNU)
	Scientific delegate representing the HCERES:
		MS Anne CAIGNARD
	Representatives of supervising institutions and bodies:
		Mr Gaëtan GELLE, Université de Reims Champagne-Ardennes
		Mr Damien JOUET, Université de Reims Champagne-Ardennes
	Heads of Doctoral School:
		M

me Nathalie LE BARCH, Doctoral School n° 547, « Science-Technologie-Santé STS » Mr Jean Claude MONBOISSE, Doctoral School n° 547, « Science-Technologie-Santé STS » 1  Introduction History and geographical location of the unit


president Michel Cosnard

Frits Mohren

Evaluation report

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

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

Management team

The former directors of EEF and LERFoB were Mr Jean-Marc GUEHL and Mr Thiéry CONSTANT respectively. For the new contract, the director will be Mr Damien BONAL and deputy directors will be Mr Thiéry CONSTANT, Mr Bruno FERRY and Mr Yves JOLIVET.

HCERES nomenclature

SVE1 Agronomie, Biologie Végétale, Écologie, Environnement, Évolution.

Scientific domains

The scientific domains of SILVA encompasses the previous domains of EEF and LERFoB: ecology and ecophysiology of trees and forests, wood science, population dynamics and management of forest ecosystems, and long-term dynamics, vulnerability, and resilience of ecosystems under changing environmental influences. The research relates to the interactions between environmental factors and forest ecosystems, which is analysed at various levels of integration, from basic processes (hydraulics, metabolism, transcripts), to higher levels (tree, ecosystem, landscape and species distribution area). Corresponding to this, the time scales comprise a wide spectrum, from short-term, near-instantaneous physiological processes to annual and multi-annual ecosystem dynamics at century or even millennium scales. The scientific focus has evolved and expanded from understanding structure and function of trees and forests in relation to species properties, functional traits, and site conditions, to integration and synthesis, the role of forest ecosystems in society in the context of global change, and the need for adaptive forest management to safeguard forest futures, and the future of the forest-based sector, the latter which is of particular economic importance in the north-east region of France.

The new unit has great potential, based on the past performance of the constituting units, the focus of the activities, and the availability of technical support and support facilities. Scientific output is abundant and of high quality, but also variable across the teams. Some individuals and groups have high international reputation and profile, and are well embedded in international networks. Others may have strong links to national forestry practice, but are less involved in fundamental, innovative research on basic concepts, and hence may have less profile internationally. The new SILVA unit has very good interactions with the socio-economic environment, but it has not yet developed strong partnership with European practitioners in forestry. The SILVA unit has an excellent infrastructure (field plots, laboratories, data management facilities including GIS), combined with opportunity for continuity in research and access to training and innovative and risk-bearing research through PhD projects and postdocs. Involvement in training is good but may still progress in terms of students and internationalisation. The organisation of the unit allows fundamental research as well as focussed, mission-oriented research and a high level of ambition, unique in Europe. There is continuity in the combination of upstream and applied research in the study of processes from the cell and organ level to the landscape level. The unit has the strong potential to become a leading research actor on the topics of long-term dynamics and tree mortality in the future, but will have to overcome the organisational and scientific difficulties linked to multisite localization.

  Marc BONNEFOND, INRA (representative of supporting personnel) Mr Federico MAGNANI, University of Bologna, Italy Mr Rupert SEIDL, University of Natural Resources and Life Sciences Vienna, Austria Mr François TARDIEU, INRA Montpellier Mr Bernard THIBAUT, CNRS Montpellier Scientific delegate representing the HCERES: Mr Serge DELROT Representatives of supervising institutions and bodies: Mr Thierry CAQUET, INRA Mr Thierry DORÉ, AgroParisTech Mr Andreas GUTSFELD, Université de Lorraine Head of Doctoral School: Mr Stéphane DESOBRY, Head of Doctoral School n°410, "Science and Engineering -Resources Process Products Environment"1  Introduction History and geographical location of the unit The UMR SILVA is a new unit resulting from a merger of the previous units UMR 1137 EEF and UMR 1092 LERFoB, that will enter into force at the beginning of the five-year plan 2018-2022. The unit combines staff from AgroParisTech, INRA (EFPA division), and the University of Lorraine. The unit is located in three geographical locations: the INRA centre in Nancy at Champenoux, the Nancy location of AgroParisTech, and the University of Lorraine at Vandoeuvre-lès-Nancy. All three sites are within 20 km of each other.

  spent at least 12 months in the unit 2  Assessment of the unit Global assessment of the unit The future UMR SILVA supported by INRA, AgroParistech and the University of Nancy Lorraine results from the merge between of EEF (UMR 1137, INRA and University of Nancy Lorraine) and LERFoB (UMR 1092, INRA and AgroParisTech). It will comprise three research teams: PHARE (Tree Physiology in Response to the Environment), TREEPoD (TREE functioning and POpulation Dynamics), and DYVE (Long Term Dynamics of Ecosystems under low Anthropization). The research teams are composed of members of both previous units (EEF and LERFoB).

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


president Michel Cosnard

François Boucher

Evaluation report

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

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

Unit name:

Signalisation

Management team

For the next contract, Mr Bruno CONSTANTIN will be the director. He will be helped by a deputy director, Ms Valérie CORONAS.

HCERES nomenclature

SVE5 Physiologie, Physiopathologie, Cardiologie, Pharmacologie, Endocrinologie, Cancer, Technologies Médicales SVE2 Biologie Cellulaire, Imagerie, Biologie Moléculaire, Biochimie, Génomique, Biologie Systémique, Développement, Biologie Structurale

Scientific domains

The general scientific objective of the STIM unit is to contribute to the understanding of the roles of membrane ionic transports in different human cells and tissues, under physiological as well as pathophysiological conditions. 2  Assessment of the unit

Unit workforce

Global assessment of the unit

The 3 teams of the unit particularly focus on the involvement of membrane channels and transporters (namely CFTR, Na + and HCN, Ca 2+ and TRP channels, connexons and Cx43) in various human primary and secondary channelopathies such as cystic fibrosis, Brugada syndrome and atrial fibrillation. The three teams of the STIM unit master an impressive number of cell physiology and cell biology techniques. They are clearly nationally and internationally recognized for this unique expertise.

There is a high quality output over the evaluated period at the level of: original publications by STIM members as first and last author, good proportion of publications in highest impact journals, limited number of publications with a low impact factor and good technology transfer activities as patents. A strong asset for further exploring technology transfer activities is the creation in 2016 of a cooperative laboratory (LitCH) that will develop its R&D inside STIM with the know-how and facilities of STIM. In addition, the unit has a good national and international reputation mainly based on the outstanding training of PhD students in the fields of physiology and electrophysiology.

The committee of experts was impressed by the high reactivity of the STIM unit following the recommendations of the previous successive evaluations by AERES in 2011, CNRS in 2014 and finally the Strategic Advisory Board in 2015. In particular, there is now a very coherent project formed by the three well-structured teams, all addressing different questions but with clear synergies. The proposed scientific foci are addressing innovative open biomedical questions.

Uncertainty remains, however, as to how the oldest generation will be replaced in the future of STIM since the attractiveness of the unit for new external scientists, in particular new young PIs, is rather low.

  location of the unitThe research unit Signalisation & Transports Ioniques Membranaires (STIM) is a laboratory with a double affiliation to CNRS (as ERL 7368 -Équipe de Recherche Labellisée) and the French Ministry of Research (as EA-7349 -Équipe d'Accueil). STIM has been created from the restructuration, in January 2012, of the former Institut de Physiologie et Biologie Cellulaires (UMR-6187 Université de Poitiers -CNRS). Up to 2012 STIM was recognized by CNRS as a Formation de Recherche en Évolution (FRE-3511) and, from January 2014 it became Équipe de Recherche Labellisée (ERL-7368). STIM is currently applying for an Inserm label.STIM is located on 2400 m 2 in the building of the Pôle Biologie Santé on the campus of the Faculty of Applied and Fundamental Sciences of the University of Poitiers. The Pôle Biologie Santé (Bâtiment B36 -TSA 51106 -1, rue Georges Bonnet -Poitiers) gathers several laboratories working in different fields of Biology and Health. It is located less than 10 min from the hospital and from the teaching rooms.

  & Transports Ioniques Membranaires

	Unit acronym:	STIM
	Label requested:
	Current number:	EA 7349 -ERL 7368 CNRS
	Name of Director	Mr Frédéric BECQ
	(2016-2017):
	Name of Project Leader	Mr Bruno CONSTANTIN
	(2018-2022):
	Expert committee members
		Ms Brenda KWAK, University of Geneva, Switzerland
		Mr Arnaud MONTEIL, University of Montpellier (representative of the CoNRS)
	Scientific delegate representing the HCERES:
		Mr Jean-Paul LALLES
	Representatives of supervising institutions and bodies:
		Mr Serge HUBERSON, University of Poitiers
		Ms Anne JOUVENCEAU, INSERM
		Mr Emmanuel LESIGNE, University of Tours
		Ms Armelle LETURQUE, CNRS
	Head of Doctoral School:
		Mr Boniface KOKOH, Doctoral School n° 524, "Biosanté"

Chair:

Mr François BOUCHER, University of Grenoble Alpes (representative of the CNU)

Experts:

Mr Hugues ABRIEL, University of Bern, Switzerland Ms Claude Marie BACHELET, University of Pierre and Marie Curie, Paris (representative of supporting personnel)

Ms Ana-Maria GOMEZ, University of Paris-Sud (representative of the CSS Inserm)


president Michel Cosnard

Philippe Huber

Evaluation report

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

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

Unit name:

Early Bacterial Virulence: cellular functions and control of acute and sub-acute infections The EA7290 "Early bacterial virulence: cell functions and control of the acute and sub-acute infections" was created in 2013 and gathered two teams of the past EA4438 and clinicians involved in infectious diseases.

Unit
The unit is located at the Institute of Bacteriology, at the Faculty of Medicine Campus of the University of Strasbourg.

Management team

Mr Gilles PREVOST was the director of the team for the previous mandature and will manage the team for the next contract.

HCERES nomenclature

SVE3

Scientific domains

In the context of fight against bacterial infection, the research unit objectives mainly focus upon Staphylococcus sp. virulence factors, and Lyme illness infective agents dealing with molecular mechanisms and identification of new factors and proteins essential for virulence and immunity. Basic research is completed by applied research on prophylaxis, diagnostic and therapeutics for bacterial infection. The unit is composed of a single team "Virulence bactérienne précoce dans les infections à Staphylocoques", and "Virulence bactérienne des Borrelia et cibles thérapeutiques".

Altogether the work made on both themes led to several original publications, conferences, reviews and book chapters, and three patents. Because of the high incidence of staphylococcal and Borrelia infections, their findings have a broad interest for clinicians, and in particular for dermatologists. The visibility on both themes is high, as underlined by the invitations of principal investigators to meetings or meeting organization committees. The principal investigators are members of editorial boards of scientific journal and participate to local and national committees of scientific and medical organizations. In the past years, the team raised enough money for their research activity and obtained subsidies for PhD students. It should be emphasized that the team made major efforts to translate its basic research results into applications, such as diagnostics or therapeutics. The projects presented by the team on both themes are logically in line with their previous findings.

All permanent researchers of the future contract have hospital and university positions, and thus invest a large part of their time in time-consuming activities (clinical duties, teaching, CNR organization,…). The recruitment of a fulltime scientist would have a major positive impact on the future projects.

  spent at least 12 months in the unit 9 Number of Research Supervisor Qualifications (HDR) obtained during the period 2  Assessment of the unit Global assessment of the unit


Report 1  Introduction Date and conduct of visit:

The site-visit of the complete AERES committee took place on Wednesday February 1 st 2012 (8:30 to 12 am) at Forum de la Faculté de Médecine, rue Kirschleger, 67000 Strasbourg. The visit started with a presentation by the head of the research unit followed by presentations by the leaders of the three projects of the unit. In three parallel meetings, members of the committee then met with PhD students and postdocs, engineers and administrative assistants, and with researchers of the two units visited that day. The morning session ended with a meeting with the unit's director and finally a closed-door meeting of the committee. In the afternoon, the committee met with the representatives of the Strasbourg University.

History and geographical location of the unit, and overall description of its field and activities:

The research unit entitled "Early bacterial virulence: cellular functions and control of acute and sub-acute infections" (EBV) results from the split of the multi-thematic EA-4438 unit and the subsequent association of two bacteriology research teams. The EBV unit focuses on the pathophysiology of acute and sub-acute infections caused by two pathogenic bacteria: Staphylococcus aureus and Borrelia burgdorferi sl. Approaches include epidemio-clinical investigations, genomic and proteomic identification of virulence factors, analysis of the cellular impact of virulence factors on target cells and assessment of new therapies.

Management team:

EBV is directed by an associate professor of the medical faculty, who heads also the research team on S. aureus. The second team on Borrelia is headed both by an associate professor and a professor of the medical faculty who is also director of the hospital bacteriology laboratory and in charge of the National Reference Center of Borrelia, two structures that directly interact with the EBV research unit. Definition and downloading of criteria: http://www.aeres-evaluation.fr/Evaluation/Evaluation-des-unites-de-recherche/Principes-d-evaluation.

Unit workforce:

Workforce

 Assessment of the unit

Overall opinion on the unit:

One of the rationales for the creation of this unit is the opportunity to gather the medical bacteriologists of the faculty of medecine of Strasbourg. This unit is relatively small but previous attempts to have a larger biomedical unit have been unsuccessful so far. There is no strong scientific interaction between the two research groups of EBV but it's a young unit and one can be confident that the director of the unit will be able to foster such interactions. It should be also stressed that discussions with the Dean of the Faculty of Medicine and the Vice-President of the University Scientific Council have shown that EBV is strongly supported by local authorities.

Strengths and opportunities:

The committee appreciates the integration in the research unit of clinicians that participate to the training of PhD students. On the other hand, the planned recruitment of a CNRS staff scientist will help to stabilize the unit. One of the members of the unit heads the National Reference Centre for Borrelia which will be of great help for the unit's research activities. In vivo experimental approaches will greatly benefit from the new animal facilities dedicated to infectious microbiology. In partnership with a private company developing diagnostic products, the unit develops several opportunities of technology transfer (e.g. anti-enterotoxin antibodies). Finally, it has developed good national and international scientific collaborations.

Weaknesses and risks:

The national and international competition on Staphylococcus aureus and Borrelia burgdorferi is very strong and thus poses a potential threat. The committee also notes that support funding is not high enough for fundamental research and needs to be reinforced. Finally, the relatively low number of PhD students and post docs of the unit hinders its research activity.

Recommendations:

The committee strongly recommends substantially improving the scientific and technological collaboration between the two research groups. This and other measures would also improve the unit's attractiveness for PhD students and post docs. The committee felt that too descriptive investigations should be avoided and that mechanistic approaches should be favored. Development of a local federation of biomedical research units is also strongly encouraged.

 Detailed assessments

Assessment of scientific quality and production:

The Staphylococcus team has good publication record. This research was reported in journals with a mean impact factor of 4.1 (range, 1.7 to 10.6), notably one of them was published in PNAS. Beside basic research, the group also developed investigations with clinicians to establish relationships between bacterial virulence factors (i.e.toxins) and staphylococci-induced pathologies (published in PLoS One and Journal of Hospital Infection), and also an antibody-based typing method for staphylococcal enterotoxins (European patent) which is a valuable tool for food industry and human medicine. The Lyme Borreliosis team has also good publication record. The group has published several papers on clinical and experimental aspects of borreliosis (2007-2011: 10 papers with 4 papers IF > 6). Since 2012, the group is the Lyme Disease Reference Center, which will further support its research.

Assessment of the unit's integration into its environment:

This research unit gathers the medical bacteriologists of the faculty of medecine of Strasbourg and is therefore fully integrated into its medical, scientific and academic environment. For instance, the director of EBV is the comanager of the master degree on Cellular and molecular pathophysiology. The Lyme Borreliosis transmitted by ticks is also an important regional health concern and therefore any scientific contribution to better understand transmission and pathogenicity may have an economic and health impact. The Borrelia team has therefore obtained support by the region Alsace.

Assessment of the research unit's reputation and drawing power:

The Staphylococcus group has a long-term, internationally-recognized expertise on toxinology (as substantiating evidence, the group leader [h-index, 32] organized, in 2009, the 14 th European Workshop on Bacterial Protein Toxins), in particular on staphylococcal exotoxins which are essential for Staphylococcus aureus pathogenesis. The two PIs of the Lyme team participate and are regularly invited to international meetings and have good international collaborations. Furthermore, the team participates in different national and international networks: Eucalb-European commitee against Lyme Borreliosis; REID: Réseau des Interactions durables: maladies à tique; CNEV: centre national d'expertise sur les vecteurs; Consortium International on mites and tick genome sequencing.

Assessment of the unit's governance and life:

The organization of the research unit is appropriate. Regular laboratory meetings are organized and the implementation of guest seminars, regular postgraduate seminar and journal club is planned . However, the scientific and technological collaboration between the two research groups should be improved.

Assessment of the strategy and 5-year project:

The project of the Staphylococcus group is a deepening investigation, through molecular and cell biology, biochemistry and cell imaging approaches of leucotoxin activity, and the mode of action of leucotoxin inhibitors and their activities in vivo using experimental models of staphylococcal infection. The group has scientific and technological expertise to develop its project. However, funding is problematic as financial support decreased during the past four years, notably compromising the renewal of obsolete equipments required for research development.

The Borrelia group focused on the role of tick saliva, the local and systemic inflammatory/immune response, local proliferation and spread of the spirochetes. The proposed investigation is sound and relevant. The contribution of the team is of good quality and may contribute to the clinical management of the prevalent Lyme disease in this Eastern part of France. Furthermore, one of the leading PIs has planned a sabbatical in San Diego to get more molecuar training for the project. However the international competition is definitively hard and the team could take benefit of the already established teams working on insect saliva and subsequent consequences upon a transmitted infectious disease.

Assessment of the unit's involvement in training:

The different members of EBV are involved in several master degrees and lectures. As teachers at the school of medicine and pharmacy, the different permanent members of the unit are involved in the Pharm D degree and Medical D degree. The director of EBV is the co-manager of the master degree on Cellular and molecular pathophysiology (35 to 40 M2 students every year). He also organizes the Master 2 examination committees. At the research unit level, regular laboratory meetings are organized to allow PhD and master students to present their research progress. The group has a long term, internationally-recognized expertise on toxins in particular on staphylococcal exotoxins which are essential for Staphylococcus aureus pathogenesis. It investigated the structure and mode of action of bicomponent toxins termed leucotoxins, which form pores in cell membranes. Notably, the group focused on interactions of the two toxin components with each other and with the cell membrane, on dynamics of pore formation and inhibition of the latter by specific antibodies and calixarenes.

The project, in continuity with past, is almost exclusively a deepening investigation, through molecular and cell biology, biochemistry and cell imaging approaches of (i) leucotoxin activity at aiming to define membrane protein ligands and target cells as well as influence of Ca2+ channels on cell signaling and inflammation, and (ii) the mode of action of leucotoxin inhibitors and their activities in vivo using experimental models of staphylococcal infection. Such a focusing research confers competitiveness to the group. Undoubtedly, the group has scientific and technological expertise to develop its project. However, funding is problematic as financial support decreased during the past four years, notably compromising the renewal of obsolete equipments required for research development. Another weakness of the group is its difficulty to recruit young researchers (including postdocs) who should revitalize it: seeking financial resources from French and European agencies should partly correct human resource deficit. The group should also increase its international visibility (its presence at international meetings must be strengthened and international collaborations should be reinforced): this should contribute to attractivity for students and postdocs from abroad.

Conclusion:

Staphylococcus is the most common Gram-positive bacterium involved in a broad range of pathologies in humans and, surprisingly, very few French research groups study bacterial virulence factors. The Strasburger group, headed by a recognized expert (strongly involved in educational activities elsewhere), is one of them, and its highquality, basic research contributed to a better knowledge in the above-mentioned field, with potential medical valorization. A better international visibilility would facilitate its financial support and, as a consequence, development of its original on going research. This proposal was the result of the fruitful dialogue between all members with the collaboration of the responsible of the scientific department from University. It also took into account the double concern to fit indications from the faculty of medicine dealing with the attractiveness of clinician colleagues and flowing in the developing tasks contributing to a scientific Federation for Translational Medicine in Strasbourg. This project reflects in fact a continued approach that consisted in the recruitment of colleagues that were considered to get interest in our fields of interest and will continue to take an active part in the next period (Pr T. Bourcier, Dr P. Riegel, Dr T. Lavigne; but also Pr Y. Hansmann, Pr D. Gaucher, Drs D. Levêque, N. Lefebvre, Dr E. Jover (CNRS-CR1).

We thank the AERES committee for his detailed analysis of the project and the report.

One major point has to be corrected: Dr N. Boulanger is assistant Professor who will be in charge of the Borrelia project, while Pr B. Jaulhac is in charge of the National Reference Center fully attributed 2012.

AERES Committee pointed out several topics:

-Financial support: in order to begin the next period in more favorable conditions, several applications were deposited this year by the different groups (2 ANR, DGA, VLM, Alsace Région…) and we are confident that a sell of one intellectual property will be achieved this year with a manufacturer involved in diagnostic. Beside of these quite usual applications, we are also willing to prepare bi-or multi-lateral applications for funding with foreign collaborators, e.g. collaborators of the Rhine Valley. Despite both the two earlier groups were regularly sustained by local funding (University, Alsace Region) that contributed to both fundamental research, PhD grants, building new animal facility, we recognized that other funding has mainly allowed to buy an FPLC, maintenance and consumables of specific programs. We hope that the new initiatives will strengthen our potential and will let possibility to buy some equipments -Publications and attractiveness: Even some were operated for past, much effort is made to get more publications in journals with IF ranking from 5 to 11-12, in a volume of more than 80 international publications. The two groups totalize 10 publications of IF > 6.0 from 2007 to date, but it would complete by 4 others this year. We also are motivated to propose consistent reviews to high ranked dedicated journals. It is right that rare funding impacts our participation to much international congresses, despite participations to "Gordon Conference on Spirochetes", "Pores 2012" and American Society for Microbiology congresses. Creation of a website and better funding would positively contribute to our visibility and possibility to recruit young researchers. For 2011 and 2012, these are 6 PhD theses that will be defensed; but among them Drs Maher Saleh and Sophie Lefèvre will stay in the team through hospital carriers, and we hope to maintain Wardi Moussaoui in a 9-12 month post-doctoral position. Otherwise, the politic of the unit will be, if possible, to sustain one application at least for a post-doctoral fellow. For the next year, we also hope to welcome 4-5 PhD students, three in the Borrelia's project, two of them are already sure.

-Scientific activities: both the two projects are interested with clinical studies that involve new clinical facts, new diagnostic approach/recommendation, pertinent new technologies, but they mainly do not affect the recurrent unit budgets. The latter studies have vocation to prepare future fundamental investigations, and may be published in good journals as mentioned by the committee. However, the budgets are mainly devoted to fundamental research that consists for:

• The Staphylococcus project aims to decipher the chronology of the various leucotoxins interactions with target cells, translocation and kinetics of calcium signals triggered in target cells. We wish to compare these elements with cell inflammatory response and examine the possibilities from different target cells that can give insights in further applications. In that sense, we will interact with the Borrelia group for their expertise with keratinocytes and fibroblasts culture and cell response.

The other facet is to define interactions of leucotoxins with receptors and also with specific antibodies and other inhibitors. The understanding of the molecular interactions may contribute to development of new effective drugs, while the efficacy of actual ones is ought to be considered. In these objectives, new collaborations are establishing.

• The Borrelia project is aware that at this point the work has been mainly descriptive. To analyze the molecular mechanisms of the transmission and being still competitive, three aspects will be developed:

- -P6-last paragraph: It is not clear to which group working on insect saliva, the AERES committee refers to. If it is the group at the IBMC working on the interaction of mosquito-Plasmodium, their area of interest concerns the innate immunity of the vector to the Plasmodium, while we work on the innate immunity of the vertebrate host to Borrelia and tick saliva. We do not exclude a future collaboration with this group, in case we develop a more specific project on the vector.

-N. Boulanger is part of a national network on arthropod saliva and is part of "Vector saliva network" headed by the NIH (National Institute of Health, Bethesda, USA).

Therefore, this project mainly deals with understanding mechanism of molecular processes in the focused objectives.

Interactions between the two groups

The further meetings between members from the whole initial project allowed delineate several common interest areas:

-

N7

  Engineers, technicians and administrative staff *on a permanent position 5 5 N5: Engineers, technicians and administrative staff * on a non-permanent position 2 (1 for 1 year) N6: Postdoctoral students having spent at least 12 months in the unit) 1 Number of producers in the 2008-2011 period who will be present in 2013-2017.

4

   Project-by-project analysis Project 1: Cell biology and inhibition of staphylococcal virulence factors Name of project leader: Mr Gilles PRÉVOST

  : cellular functions and control of acute and sub-acute infections (EBV) -Dir: G. Prévost Université de Strasbourg Comments of the AERES report dated February 2012, receive March 23 rd 2012 Despite initially constituted of three research groups the project now gathers two groups with the same initial personnel that are called: -Cell biology and inhibition of staphylococcal virulence factors, PIs G. Prévost, F. Jehl (assistant Professors) -Cellular and molecular biology of tick-borne infections, PIs N. Boulanger (assistant Professor), B. Jaulhac (PU-PH)

  Skin microbiome and TLRs with Pr R. Gallo (San Diego) -Host vascular permeability and development of the disease with Dr L. Bockenstedt (Yale university) and with Dr T. Moriarty (Toronto University) to analyze this process by confocal intravital microscopy -Role of resident skin mast cells with Dr. S. Mécheri (Pasteur institute, Paris).

  Influence of bacterial flora according to moisture on tick bite localization -Influence of staphylococcal product interacting with TLR-6 on Lyme disease development -Influence of Borrelia on cell calcium levels, involvement of major calcium pathways -Establishing a cell model derived from neuroborreliosis -Confocal microscopy, multiplex titrations, where the two projects would produce common work and can gain interactions. Strasbourg, 02.04.2012 G. Prévost

6 

 6 Statistics per field

	Notes
		C1	C2	C3	C4
	Critères	Qualité scientifique et production	Rayonnement et attractivité, intégration dans l'environnement	Gouvernance et vie du laboratoire	Stratégie et projet scientifique
	A+	10	14	18	16
	A	33	32	31	29
	B	13	10	6	11
	C	1	1	2	1
	Non noté	-	-	-	-
	Pourcentages
		C1	C2	C3	C4
	Critères	Qualité scientifique et production	Rayonnement et attractivité, intégration dans l'environnement	Gouvernance et vie du laboratoire	Stratégie et projet scientifique
	A+	18%	25%	32%	28%
	A	58%	56%	54%	51%
	B	23%	18%	11%	19%
	C	2%	2%	4%	2%
	Non noté	-	-	-	-

Project 2:

Cellular and molecular biology of tick-borne infections Name of project leader:

 Detailed assessments

The group combines clinical and experimental murine studies to obtain new insights into the pathogenesis and epidemiology of borreliosis. Since this disorder is of great medical importance in France, especially in Alsace, their work is highly clinically relevant. In the following 5 years, the group will focus on the interaction of Borrelia with the skin, in particular keratinocytes, and the modulation of this interaction by tick saliva.

A major finding of this small unit was that vector (tick) saliva downregulates the cutaneous inflammatory response induced by invading Borrelia, which may support survival and spread of Borrelia in its new host. To further study this important aspect, the group has set up in vitro models with human keratinocytes, mast cells and fibroblasts as well as a murine model of Borreliosis, which both are straightforward to further characterise (i) the effect of the vector saliva on the local and systemic inflammatory/immune response and (ii) influence of tick saliva on spread of different Borrelia species in the skin. These proposed investigations are sound and relevant. The approach is original and the team is aware of the strong international comptetition.

In the past, the team has obtained support by the region Alsace and DGA (Direction Générale de L'armement) for two of the PhD thesis. Furthermore, the team is well integrated in different national and international networks (Eucalb-European commitee against Lyme Borreliosis; REID: Réseau des Interactions durables: maladies à tique; CNEV: centre national d'expertise sur les vecteurs; Consortium International on mites and tick genome sequencing). The proposed project will be performed in collaboration with national and international colleagues, which will further contribute to the international visibility of the group. The latter is also documented by invitations of the project leader as speaker to international conferences.

Conclusion:

The Borrelia group has a good scientific productivity and links clinical and experimental research. The project for the following 5 years is focussed, solid and well planned. Currently, the group is relatively small and it will be important to enlarge the group with PhDs and Postdocs to further increase productivity, to augment the scientific atmosphere, the international visibility, and competitiveness.

 Grading

Once the visits for the 2011-2012 evaluation campaign had been completed, the chairpersons of the expert committees, who met per disciplinary group, proceeded to attribute a score to the research units in their group (and, when necessary, for these units' in-house teams). This score (A+, A, B, C) concerned each of the four criteria defined by the AERES and was given along with an overall assessment.

With respect to this score, the research unit concerned by this report (and, when necessary, its in-house teams) received the overall assessment and the following grades:

Overall assessment of the unit "Early Bacterial Virulence: cellular functions and control of acute and sub-acute infections EBV":

Unité dont la production, l'organisation et l'animation sont très bonnes. Le rayonnement et le projet sont bons mais pourraient être améliorés.

Grading table:

C1

Scientific quality and production.

C2

Reputation and drawing power, integration into the environment.

C3

Laboratory life and governance.

C4

Strategy and scientific project.

A B A B


president Michel Cosnard

Jean-Luc Bailly

Evaluation report

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

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

Unit name:

Viral cardiovascular infections and inflammatory response in human pathologies

Unit acronym: CardioVir

Label requested:

INSERM

Management team

The unit is headed by Mr Laurent ANDREOLETTI.

HCERES nomenclature

main scientific domain: P3 (Life and environmental sciences); -secondary scientific domain 1: SVE3 (Microbiology, Immunity); -secondary scientific domain 2: SVE2 (Cellular biology, Imaging, Molecular biology, etc.); -secondary scientific domain 3: SVE5 (Physiology, Pathophysiology, Cardiology, etc.).

Scientific domains

The domain of activity of the unit corresponds to the disciplinary areas of virology and pathophysiology. The scientific research is related to human health, infectious diseases of the heart caused by viruses, and the study of hostpathogen interactions at the molecular and cellular levels. 2  Assessment of the unit

Unit workforce

Global assessment of the unit

CardioVir is a mono-thematic unit, which develops a research in virology aimed at understanding the pathophysiologic processes involved in virus-induced chronic cardiomyopathies, using chronic enterovirus infection as a model. Other etiological agents, i.e. herpes viruses and parvovirus B19, involved in acute myocarditis, are also studied.

The CardioVir unit is based on a fruitful local multidisciplinary collaboration between 4 disciplines (virology, anatomopathology, cardiology, and infectious diseases). The positive environment (scientific focus, facilities, and equipment) was favourable to risk-taking research investigating the role of viruses (notably enteroviruses) in chronic cardiomyopathy. The milestones in the research activity of the unit were: (1) the development of quantitative and qualitative molecular tools to detect enterovirus genomes and their replicative forms in human cardiac tissues; (2) the use of these molecular tools as diagnostic techniques in fulminant myocarditis and sudden cardiac death cases; (3) the comparison of molecular markers (CD3, CD68 and HLR-DR) expression in patients with enterovirus or parvovirus B19 infections; (4) the construction of a chimeric coxsackievirus B3 harbouring em-GFP to study genome replication in human cardiomyocytes; (5) the biobanking of peripheral blood and cardiac tissue samples for healthy subjects and patients; and (6) the contribution for virology expertise in clinical multicentric trials and registries for acute myocarditis, chronic dilated cardiomyopathy and cardiac sudden death.

The unit has good scientific track records. The members have authored original publications in peer-reviewed scientific journals covering different disciplinary fields (clinical microbiology, infectious diseases, and cardiovascular research). The leading journals were Circulation, Emerging Infectious Diseases, Heart Rhythm, and the Journal of Clinical Microbiology.

The unit staff is reduced and includes only members (PU-PH) with regular teaching duties and hospital activities. However, there is active training through research.

The unit is recognized at the international level for its contributions on the border between clinical virology and basic virology in the field of heart chronic infections. The unit is the only french group studying human cardiac diseases caused by enteroviruses.

CardioVir develops a unique and original niche of excellence in virology. In the future, the strategy of the unit is to investigate viral cardiovascular infections and the inflammatory responses in human pathologies.

  location of the unitThe unit EA 4684 (CardioVir) was created in 2012 with members of the former unit EA 4303 (team 4), which was shut down. The CardioVir unit is under the supervision of the University Champagne-Ardenne -Department of Medicine and also the University hospital (CHU) of Reims. It is located in the Faculty of Medicine in close vicinity of the University hospital.

Qualified research supervisors (HDR) or similar positions Unit record From 01/01/2011 to 30/06/2016

	PhD theses defended	2
	Postdoctoral scientists having spent at least 12 months in the unit	1
	Number of Research Supervisor Qualifications (HDR) obtained during the period	5
	Unit workforce	Number on 30/06/2016	Number on 01/01/2018
	N1: Permanent professors and similar positions	5 (1.5 FTE)	5
	N2: Permanent researchers from Institutions and similar positions	9 (3.1 FTE)	8 (2.8 FTE)
	N3: Other permanent staff (technicians and administrative personnel)	2 (0.7 FTE)	2
	N4: Other researchers (Postdoctoral students, visitors, etc.)
	N5: Emeritus
	N6: Other contractual staff (technicians and administrative personnel)
	N7: PhD students	3
	TOTAL N1 to N7	19 (8.3 FTE)


president Michel Cosnard

Muriel Moser

Evaluation report

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

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

Unit name:

Immunology, Immunopathology and Therapeutic Chemistry

Management team

The current director is Ms Sylviane MULLER. The new unit will be managed by Ms Hélène DUMORTIER as director and Mr Alberto BIANCO as deputy director.

HCERES nomenclature

SVE3

Scientific domains

The unit is dedicated to the study on autoimmune phenomena and the search of innovative solutions of therapeutic intervention with synthetic peptides. The research focuses mainly on Systemic Lupus Erythemathosus (SLE) and related disorders. The unit's topic is focused on autoimmune phenomena. The main scientific interest of the unit was to develop their own transgenic models to investigate fundamental cellular and molecular processes of tolerance as well as therapeutic approaches. Its objectives were to manipulate the immune system of: (i) autoimmune prone mice to interfere with the course of the disease or (ii) of normal mice to make them susceptible to the disease. The unit also studied human patients thanks to clinicians performing research in the unit.

Since the last report, the unit developed new technological skills thanks to new recruitments, in the field of cheminformatics and bioinformatics, advanced technics in molecular, cell and small animal imaging and animal behavioural studies.

The strength of the unit resides in the fact that they perform both fundamental and translational research and study in parallel animal models and human patients. Of note, they have developed original transgenic murine models. In addition their research is transdisciplinary. However, a weakness is that most articles during the reference period were only published in good-to very good international journals.

The unit has very good fundraising capacity (including european contracts, ANR, CNRS, foundations, regional and industrial contracts) and is part of the labex Medalis and labex CSC (Chimie des Systèmes Complexes). The unit showed exellent technology transfer capacity, training quality, and attractivity for foreign students as assessed by the recruitment of foreign post-docs in the past 5 years. This is a very good unit that proposes an excellent project for the future, although the high diversity of projects may need a prioritization.

  location of the unit The unit "Immunopathology and Therapeutic Chemistry, ICT" is part of the Molecular and Cellular Biology Institute, IBMC, located at the central university campus Esplanade in Strasbourg. The current unit derives from a previous unit, created in 1993, named Immunochemistry of peptides and viruses -IPV, UPR9021, directed by Mr Marc VAN REGENMORTEL until 2000. ICT, UPR9021, was created under the direction of Ms Sylviane MULLER in 2001 and renewed twice, in 2005 and 2009. In 2013, ICT was created as UPR 3572 in its present configuration.

  spent at least 12 months in the unit 14 Number of Research Supervisor Qualifications (HDR) obtained during the period 2  Assessment of the unit Global assessment of the unit