Grading

Once the visits for the 2012-2013 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 six criteria defined by the AERES. NN (not-scored)

 Introduction History and geographical location of the unit

The Inserm/Institut Curie U830 was created on January 1 st 2007 and was located in the building Pavillon Trouillet-Rossignol at the Paris site of the Institut Curie. This unit derives from the merging of two former units : the Inserm/Institut Curie U 509 (Molecular Pathology of Cancer; director Mr Olivier DELATTRE) and the Inserm/Institut Curie U528 (Signal Transduction and Oncogenesis; Director Mr Jean de GUNZBURG). One of the goals of this fusion was to associate groups developing complementary research lines on molecular bases of human cancers and on animal modeling of oncogenic processes. At its creation, the U830 was composed of 6 independent teams and was directed by Mr Olivier DELATTRE. Mr Alain AURIAS who was the Head of the group working on adult sarcomas retired in 2010. Ms Françoise MOREAU-GACHELIN who heads the team "Leukemogenesis and spi transcription factors" will also retire in 2013. Thus, among the 6 pioneer groups of the U830, four apply to the renewal application of this Unit, ie :

Team1 : "Genetics and biology of paediatric cancers" (Dir : Mr Olivier DELATTRE) Team2 : "Analysis of transduction signals" (Dir : Mr Jacques CAMONIS) Team 3: "Stress and cancer" (Dir. Ms Fatima MECHTA-GRIGORIOU) Team 4: "Genetics and biology of hereditary breast cancers" (Dir: Mr Marc-Henri STERN) An International call to recruit a junior group leader was launched in 2010. However, the two candidates that were selected out of 60 applicants did not join the U830 eventually. Since the teams of the U830 have to face a laboratory space constraint, especially Teams 3 and 4, it has been decided to postpone a new call for a junior position. Indeed, the U830 is distributed on 3 floors and approximately 900 m 2 are available for more than 70 persons working in this Unit. Since 3 clinicians working in the U830 on a "Contrat d'Interface Inserm" should join the "Translational Department" of Institut Curie, it is expected that more space lab will be available in 2013. In this context, 2 clinicians, currently working in the U830 have been selected to create a "translational" group in the frame of the recently created SIRIC (Sites de Recherche Intégrée sur le Cancer de l'Institut Curie directed by Mr Olivier DELATTRE). Therefore, these 2 clinicians will move their research activities to the Hospital part of the Institute. Thus, in its new configuration, the U830 will be composed of the 4 groups aforementioned to which a new team headed by a junior group leader, who has yet to be hired, will be associated during this five-year contract.

Before coming into the details of the evaluation, the Committee emphasizes that this report is strictly focused on the U830 teams that apply for the contract renewal. However, the Committee members wish to express their collective esteem to the the researchers who left the U830 for their scientifif achievement. Their dedication and remarkable contributions to the biomedical research shall be praised.

Management team

The current Director is Mr Olivier DELATTRE (DRCE, Inserm) and he will be renewed in his functions for this 5year Contract. The former Deputy Director was Ms Françoise MOREAU-GACHELIN and she will be replaced at this position by Ms Fatima MECHTA-GRIGORIOU. A steering committee composed of the group leaders meets once a month to discuss administrative, organizational and scientific topics. In addition, a "Unit Committee" shall meet once a year and includes group leaders, representatives of staff scientists, students, technician and administrative personals. All collective issues regarding the organization of the Unit (collective tasks, responsibility for equipments…) are discussed during this Committee. In addition, scientific meetings to which all the U 830 members are invited to attend are organized once a week. Finally, two agents in charge of the Health and Security issues have been nominated and work on the 3 rd and 6 th floor of the building hosting the Unit. The budget policy of the Unit was not explicitly described in the application. The overall quality of the scientific production of the U830 is first-rate and the contribution of the teams to the various topics studied is nationally and internationally renowned.

AERES nomenclature

Unit workforce

Unit workforce

2.

Most of the scientific projects are well-thought, address cutting-edge questions, are based on skilful groups and supervised by group leaders with a recognized leadership.

3.

Opportune collaborations between groups of the U830 that have led to the development of two transversal research programs.

4.

Excellent interactions of the U830 teams with the clinicians of the Institut Curie allowing the organisation of collaborative projects and programs that create the conditions of a strong synergy.

5.

Competitiveness in funds raising at a national level, but also at an International level (participations of several teams of the U830 to 6 EC programs).

6.

Outstanding platforms at the Institut Curie (imaging, functional genomics, animal facilities…) are made available to the members of the U830. In addition, one of the lab scientists is at the initiative with a colleague at the Institut Curie of the creation of BioPhenics, a cell-based high throughput screening platform.

7.

The U830 teams will have access to the Next-Generation Sequencing (NGS) tools with the creation of the Equipex ICGex (Equipement de biologie intégrative du cancer pour une médecine personalisée), a program coordinated by Mr Olivier DELATTRE.

Weaknesses and threats

1.

The groups are heterogeneous in terms of structure, and in most cases (besides the case of Team 1), are not balanced between scientists with permanent positions (CD, DR and professor-researchers (MCU, PR, MCU-PH, PU-PH) and ITA, post-docs and students. In this respect, Fatima Mechta-Grigoriou's support to the application at CNRS/Inserm of a post-doc from Team3 who has been granted an "ANR jeune chercheur" goes in the right direction.

2.

The visiting Committee noticed the underrepresentation of professor-researchers of Paris 5 University in the U830 that should be improved.

3.

As already underscored, the U830 is confronted to a limitation of lab space that restricts the capacity to attract new groups and hampers the reinforcement of the U830 scientific dynamics.

4.

The high-throughput technologies and genome scale analyses require the recruitment of bioinformaticians to treat large volume of data. Bioinformatics has become a stumbling block for all laboratories working in the "omics" field. The director and group leaders of the U830 have clearly stated that the full development of their research programs relie on the hiring of scientists with this kind of expertise.

5.

The management procedures in the Unit should be optimized. Discussions of the visiting committee with members of the personal have revealed that the information related to the scientific strategy of the unit and on other questions that directly concern the daily work of the personal is not always shared.

Recommendations

The Committee has been impressed by the overal quality of the U830 teams which have demonstrated their scientific proficiencies during the former contract. However, considering the excellent reputation of the U830 as well as the privileged scientific surrounding of this Unit (nearby Units at Institut Curie and on the site of La Montagne Sainte-Geneviève), the Committee considers that the U830 did not harness on these assets to recruit scientists with permanent positions (CR/DR positions or MCU/PR) or new group leaders. This constatation is the basis of the major recommendations of the Committee detailed below.

Accordingly, the Committee supports the attempt to recruit a junior group leader. Even if the strategy to limit the coming of a novel group for space constraints reasons is wise in a medium-term (a situation that should be clarified during the course of 2013), the Unit should take advantage of its attractivness to hire a new group leader as it was initiated but discontinued.

During the on-site visit, the Committee has been informed by the Director of the Research at the Institut Curie and by the representative of Paris 5 of their policy regarding their institutional association, especially in the frame of the former and future 5-year contract of the U830. However, the Committee felt that, whatever the historical conditions of this partnership are, they should not prejudice the group leaders of the U830 in their effort to recruit professors nor refrain their involvement in teaching activities at Paris 5. Strenghtening the bonds between the U830 and Paris 5 is advocated by the Committee members and would create opportunities for positions to inside or outisde post-docs as it would contribute to the stabilization of the existing groups.

The recognition of the U830 as well as the possibility to apply for fellowships at the Institut Curie (or french agencies/charities) should create incentive conditions to attract post-docs with a very good track record that would be eligible for a CR position.

The Committee has appreciated the synergies between groups of the U830 that have led to the setting up of transversal projects. The Committee strongly encourages the director to foster these initiatives and group leaders/scientists with permanent positions to go further in that direction that is a valuable catalyzer of the unit dynamics.

An effort shall be made to improve the sharing of information between the "steering committee" and the rest of the unit. Following this line of thinking, the gathering of the "Unit Committee" once a year is a too infrequent periodicity and should be call to meet at least twice a year.

 Detailed assessments Assessment of scientific quality and outputs

The U830 covers several fields of research in oncology, namely the study of the genetic and biological bases of pediatric cancers, as well as inherited breast and ovarian tumors. In addition, both the signalling networks involving the Ral small G proteins and the contribution of the chronic oxidative stress to the transformation processes are the focus of the U830 scientific projects. If we consider that these topics are the subject of an intense competition at an international level, it is truly remarkable that the 4 teams were all successful in their undertakings, producing original data and making several seminal discoveries that were published in the top jounals in biology. During the past 5 years, members of the U830 have published 276 articles (this number is the summation of papers in which the U830 investigators are the main contributors as well as associated papers); fourty of these articles have an impact factor superior to 10. If the main publications of the group are referenced, Team 1 has published 28 articles including papers in Cancer Cell, Nature, Nature Genetics, J Clin Oncol, Cancer Res, Oncogene; Team 2 has published 5 articles including Mol Cell, Plos Biol, EMBO J; Team 3 has published 3 papers in Cell Metabolism, EMBO Mol Medicine, Nature Medicine; Team 4 has published 18 articles including Blood, Cancer Res, J Clin Oncol.

Assessment of the unit's academic reputation and appeal

During the 5-year contract, team leaders of the U830 and other members of the teams attended national and international conferences as invited speaker : Team 1 : 80 invitations to give seminars in France and abroad; Team 2: 4; Team 3 : 19; Team 4 : 23. All team leaders review articles for scientific journals including Nature, Cell, Cancer Cell, New England Journal of Medicine, Am J Hum Genet... They also participate to the scientific committees of french and foreigner agencies/charities (ARC, Ligue Nationale Contre le Cancer, ANR, FRM, AICR,…) but also to the scientific councils of several Centres/Institutes (Fondation Jean Dausset, Centre Léon Bérard, Institut Paoli-Calmettes, board Oncogénétique de l'INCa…). Mr Olivier DELATTRE is the director of the SIRIC, the Coordinator of the ICGex program and he is also involved in the development of the Translation Research Department at the Institut Curie.

Heads of the groups and staff members of the groups are regularly invited to give seminars at national/international conferences (>130 invitations all unit members included during the 5-year contract) and they participate also to international consortia (6 EC programs associate U830 teams), coordinate several national research programs (INCa, INCa-DHOS, ANR, 2 Programmes Incitatifs et Collaboratifs (PIC) and are involved in the Cancéropôle Ile-de-France. All team leaders as well as members of these groups have received prizes and distinctions (Académie des Sciences; Académie de Médecine, Simone and Cino del Duca Prize, Prix du Ruban Rose, Eurocancer, Grand Prix Charles Oberling) that attest of the recognition by the national/international communities of the scientific reputation of the U830. Moreover, several members of this Unit have been involved in the organization of scientific meetings : International Course on breast cancers, Institut Curie, 2011; annual breast cancer day by Institut Curie, 2011, Colloque "Petites protéines G", Mouans-Satoux, 2008; co-organisation of regular meetings on "Dynamique, Instabilité Génétique et Oncogenèse; organization in 2012 of 3 gatherings of International Consortia on the genetics of breast cancer. Finally, another indicator of the U830 appeal is the recruitment of post-docs and according to this criteria the U830 is well-positioned since 21 post-docs joined the Unit during this contract.

Assessment of the unit's interaction with the social, economic and cultural environment

Several members of the Unit gave interviews to the french television (TF1, France 3) as well as to local chanels, videos and news papers. Four patents have been filed during the 5-year contract.

Assessment of the unit's organisation and life

Mr Olivier DELATTRE is highly experienced in the direction of a laboratory, has a charismatic leadership and has made several breakthroughs in the genetic bases of pediatric cancers. Furthermore, being both a MD and a PhD, he is highly committed in the structuration of biomedical programs.

The organization of the unit is based on independend groups, each headed by a team leader. The decisionmaking body is the steering Committee that includes the Director, the Deputy-Director and the group leaders that gather once a month. A "Unit Committee" meets once a year and includes group leaders, representatives of staff scientists, students and ITA personals. All collective issues regarding the organization of the Unit (collective tasks, responsibility for equipments…) are discussed during this Unit Committee. Scientific meeting are also organized once a week and all members of the U830 are invited to attend these seminars.

During the encounter of the Committee with staff scientists, ITA and post-doc/students, the comments expressed on the conditions of work and on the scientific life were generally positive. However, as already emphasized in this report, the researchers felt that several important decisions that directly impact on the functioning of the Unit and consequently on the organization of the work were not adequately shared between the steering committee and the personal of the Unit. Thus, an effort should be made to rationalize the transmission of the information within the U830 and the Committee proposes that the Unit Committee meets more frequently. Alternative like a written report following each steering committee that would be addressed to the whole Unit should be thought after.

Finally, the emergence of young investigators towards leadership (autonomous demands of funding, tutoring of students, co-autorship policy with the articles) is promoted in the U830, a fact confirmed by their independent oral presentations during the on-site visit.

Assessment of the unit's involvement in training through research

22 PhD students successfully defended their thesis during the 5-year contract which is an indicator of the good quality of the tutoring of the students in the U830, especially if we consider that 9 scientists of the Unit have their HDR (3 members of the U830 obtained their HDR during this 5-year contract). Furthermore, the majority of the students published from 1 to 35 publications during their thesis. In addition, 16 M1 and 22 M2 students did their training period during this contract and 11 students (Ecole d'Ingénieur, others…) worked also in the Unit during these 5 years. The majority of the U830 staff scientists are also involved in teaching activities in Masters : Master Paris 6 (Biologie Moélculaire et Cellulaire), Master Cancérologie Paris XI…

Assessment of the five-year plan and strategy

The director and the steering committee have decided to discontinue the projects focused on adult sarcomas and leukemogenesis because of the retirement of both involved team leaders. The rationale of this decision is to use the lab space available to favor the extension of two existing groups (Teams 3 and 4) and to recruit a junior group leader. In addition, two clinicians who presently work in Team 1, will constitute an independent translational research group in the frame of the recently created SIRIC. These choices concerning the future composition of the U830 are sound and received full support from the Committee as expressed in the Recommendations. Furthermore, two translational projects internal to the U830 have been established between Team 3 and both Team 2 (autophagy) and Team 4 (stress, genetic instability and cancer). Also, the scientific activity of Team 1 will be refocused on the study of the genetic and biological bases of pediatric tumors and the program on sporadic breast tumors will be terminated. Similarly, the research of Team 4 will be dedicated to hereditary breast cancers and the program on T-cell prolymphocytic leukemia will be wound up. Finally, Team 2 will pursue his line of research on the role of Ral GTPases in oncogenesis while Team 3 will continue the project on the relations between stress and cancer development but with a marked orientation on the study of tumor microenvironment and ovarian neoplasia. Overall, the Committee found that these five-year plans are well-founded, consistent with the expertise of the Unit and are expected to reinforce the innovative contribution of the U830 to basic research but also to the translation of scientific findings into the clinics. In this respect, The U830 is at a favourable position to succeed in its endeavour due to the scientific skills of the teams but also because of the propitious location of the Unit that has access to collaborative clinical departments of the Institut Curie as well as to state-of-the art genomic tools. However, even if this evaluation is globally very positive, the Committee would like to draw the attention of the Director and the group leaders to circumbscribed concerns on strategical choices that are detailed in the evaluation Team by Team and ought to be addressed.

4  Team-by-team analysis

Assessment of the unit's academic reputation and appeal

The team has an established international reputation in the field. Mr Olivier DELATTRE is considered as an international expert in Ewing sarcoma, rhabdoïd tumours and neuroblastoma. This reputation is illustrated by his active participation to numerous international scientific committees and reviewing for very high impact journals, such as Nature or Cell. The attractiveness of the team is also illustrated by the regular recruitment of post-docs, invitations to international meetings and its active participation to 6 European projects.

Assessment of the unit's interaction with the social, economic and cultural environment

Mr Olivier DELATTRE is strongly involved in several national scientific committees of national institutions such as INCA, Inserm, ANR or of French Comprehensive Cancer Centres which, therefore, benefit from his scientific inputs. The link of the Unit with the translational department of Intitut Curie allows a transfer of basic knowledge to the clinics. Mr Olivier DELATTRE played a key role in the success of Institut Curie in national funds raising (Equipex, SIRIC).

Assessment of the unit's organisation and life

The scientific and personal leadership of the team leader was unanimously recognized by all of his team.

Assessment of the unit's involvement in training through research

The team has a sustained activity in the training through research: the team has trained 10 master students and 11 PhD.

Assessment of the five-year plan and strategy

The team will focus its projects on pediatric tumours, Ewing sarcoma, rhabdoïd tumours and neuroblastoma in the continuation of the previous work, by combining high throughput genetic analyses to characterize network deregulated in these tumours and functional studies based on cellular and genetically modified mice. The project is solid, will benefit from the high quality technological platforms in Institut Curie and international collaborations.

Conclusion  Strengths and opportunities:

-Scientific excellence, -International reputation, -International expertise, -Permanent success in national and European French raisings.

 Weaknesses and threats:

-The limited number of researchers with permanent positions considering the number of topics, -The difficulty to offer permanent positions to young scientists due in part to the limited space in Institut Curie, -The difficulty to recruit permanent highly qualified bioinformaticians whose expertise will be critical for the success of the scientific projects.

 Recommendations:

-Recruitment of scientists with permanent positions, -Maintenance of tight links with clinicians in order to maintain the quality of patient recruitment, the possibility to perform efficient pre-clinical investigations and to ensure an efficient transfer of the knowledge for the patient benefit. The position of the "translational research group" and its connection with the unit and the translational department of Curie should be clarified, -Considering the excellence of the group, the bonds with the university should be strengthened.  Detailed assessments

Assessment of scientific quality and outputs

The group has gained a strong international reputation on the decipherment of Ras-like signaling pathways, mainly using biochemical tools for the detection of protein interaction and by using the drosophila model for functional studies. Considering its small task-force [8 people : 2 PhD students, 2 post-docs, 3 technicians], the group has demonstrated a very good level of scientific production: 21 research articles published between 2008 and 2012, many of which in rank A journals [J. Cell Biol.; Mol. Cell; Cell; Cell Reports; Nature Methods; PLoS Biol.; EMBO J.]. The committee has unanimously acknowledged the high scientific quality of this team.

Assessment of the unit's academic reputation and appeal

The group is internationally recognized in the Ras field. Group members have been invited to national and international meetings. The group leader participates to the scientific committee of the ANR Biotechnologies agency and co-heads the Biophenics platform at the Curie Institute. The group has been well funded for the considered period as it has obtained regularly major national research grants and salaries from governemental agencies and from charities. However, there is no funding granted beyond 2013, and the group suffers from a deficit of experienced researchers with a permanent position.

Assessment of the unit's interaction with the social, economic and cultural environment

As a founder member and scientific expert, the group leader has greatly contributed to the success of the biotech Hybrigenics.

Assessment of the unit's organisation and life

The group is highly involved in helping the career development of students and post-docs. Two post-docs have got permanent positions as assistant professors in France and Portugal.

Assessment of the unit's involvement in training through research

The group has housed 9 trainees, 7 PhD students and 5 post-docs since 2007. The group leader gives courses at the M2 level.

Assessment of the five-year plan and strategy

In the next years, the group leader wants:

-to deepen the analysis of Ral activity, in particular in the Hippo pathway, in cell migration and in autophagy, and besides, -to develop further the high-throughput Biophenics platform towards automatic detection and measurements of phenotypic changes associated with si-RNA or drug treatment. The latter project is of high importance for the scientific community of the Curie Institute and beyond.

Although the projects proposed are in the field of expertise of the group, the committee expressed some concerns about the adequation between the number of projects and the team task-force. Also, the identification of the goals that are going to be investigated during this new contract were not always completely convincing. Thus, there is a clear need in the nearest future to identify the major scientifc aims, to prioritize the defined projects and to stabilize the group with the recruitment of scientists with permanent positions.

Conclusion  Strengths and opportunities:

The team is led by a very dynamic PI who has gained an international reputation on protein interaction and developed many long-term and fruitful collaborations. The PI also co-heads an efficient Automated Cell-based High Throughput Screening Platform (Biophenics).

 Weaknesses and threats:

The team has been funded by many contracts (as coordinator ANR, ARC, PIC, foundation de France and INCa and as partner PIC), most of which will stop in 2012. This may be a concern although the high quality of the scientific production should warrant funding for the next years.

Several postdoctorants got permanent positions elsewhere and have thus left the lab. Together with the departure of the scientists in charge of analysis of Ral signaling in Drosophila, this may be a threat for the stability of the team and the success of the proposed projects.

 Recommendations:

The group should adapt its projects to the size of its task force.

The recruitment of a permanent researcher would improve stability of the group.

 Detailed assessments Assessment of scientific quality and outputs

The team has been created in 2006 following obaining an Avenir grant by the group leader. Until recently, Team 3 remained a small group of 4-5 people. New space has recently been dedicated to this group, allowing it to increase its size to 8-10 people. The group studies the pathophysiological consequences of chronic oxidative stress. Despite its small size, the group made very significant discoveries and, consequently, achieved an excellent publication record, with regular own publications in excellent journals such as Cell Metabolism, Nature Medecine and EMBO Molecular Medicine, as well as a number of collaborative publications. The committee has unanimously recognized both the quality and interest of the work produced.

Assessment of the unit's academic reputation and appeal

The group is clearly among the national leaders in its field, and has gained a very strong international reputation. The group leader is regularly invited to national and international meetings. She participates in several french scientific committees, both from governemental agencies (INSERM or CNRS committees) and from charities (ARC). A few students from the group obtained national prizes. The group is well funded and obtained regularly major national grants from governemental agencies and from charities. As a weakness, it has to be noted that the group did not attract experienced researchers with a permanent position from a french governemental agency.

Assessment of the unit's interaction with the social, economic and cultural environment

The group leader has been involved in many events linked to scientific popularization and diffusion to a general audience. The group leader obtained an incitative grant from the Curie Institute, together with a Physicist, to develop a common facility to perform a deep analysis of the tumour microenviroonment. There are discussions going on with private companies to secure this facility at the end of the 3 years of funding. The group has filled one patent.

Assessment of the unit's organisation and life

This is clearly a major strength of the group. The group leader is highly involved in helping the career development of students and post-docs working with her. Of note, most of the PhD students and post-docs obtained a high-impact first author publication from their work in the group. The scientific and personal leadership of the head of the group was praised by all members of her group.

Assessment of the unit's involvement in training through research

The group has recruited 4 M2 students, 4 PhD students and 4 post-docs since 2007. Most of the PhD students and post-docs obtained a high-impact first author publication from their work in the group. The group leader has been in charge of an european course on Breast Cancer. She gives courses at the M2 level (about 4 hours per year). Other members of the group, including PhD students and post-docs also particpate in M1 courses (2 for 5hours/year), and 1 is "moniteur" at the L2 level.

Assessment of the five-year plan and strategy

In the next few years, the group leader wants to develop her activity in two main directions: firstly, she intends to pursue along the lines opened by her recent publication on the two types of ovarian cancer (the "oxidative stress" and the "fibrosis" types), developing fundamental studies to better understand the differences between these two types of ovarian tumours (through global proteomic or metabolomic analyses, but also through studies on selected proteins (MAP3K8) or at the biology/Physics interface on the role of mechanical constraints). The team leader also plans to develop applied research dedicated to the development of drugs or pronostic tools specific to patients with an ovarian cancer with a "fibrosis" or "oxidative stress" profiles. Secondly, she wants to go on working in the field for which the research group has a proven strong expertise, which is the mechanisms of oxidative stress regulation and how it is linked to tumor outgrowth.

There is no doubt that the questions the group leader wants to tackle down are relevant oncological questions. The second part of the project on oxidative stress corresponds to the group proven expertise and will undoubtedly lead to major findings. In addition, the orientation to applied research is well thought, valuable and received full support by the Committee. However, while the Committee has been convinced by the global phenotypic approaches previously used by the group to discriminate between "fibrosis" and "oxidative stress" ovarian tumours, including proteomic and metabolomic approaches, there were concerns about the benefit for the group to come back to classical "gene-based" strategies relying on individual markers (such as MAP3K8) of ovarian cancers. Moreover, the committee was unsettled by wide spectrum of proposed projects (although all very interesting and well-thought), stressing a need to prioritize the projects in the near future.

In summary, the project proposed by this group is of very good quality, imaginative and deserves to be supported.

Conclusion:

 Strengths and opportunities:

-The expertise and track record of the group in their research field, -The ability to perform imaginative research, -The quality and originality of the various research projects, -The opportunities provided by the Curie Institute environment both for fundamental and applied research, -The qualities of the collaborations set up by the group both at the Department, at the Curie Institute or outside.

 Weaknesses and threats:

-The lack of researchers on permanent positions in the group, -The small size of the group to be competitive on many different research projects.

 Recommendations:

-The research plan would benefit from prioritization of the various projects, -The recruitment of a permanent researcher from the CNRS or the Inserm would improve the group efficicency.

 Detailed assessments

Assessment of scientific quality and outputs

The team of Mr Marc-Henri STERN has a staff of 10-14 people, with 5 with a permanent position. Team 4 studies inherited breast cancer. More particularly, this team has characterized a consistent series of BRCA breast cancers by using pre-NGS genomic analyses and established a new BRCA-associated parameter of genome status called Large Scale Transitions, which could be used in clinics to identify familial cases to sequence further and perhaps could predict therapeutic response to PARP inhibitors and platinum salts. They have recently identified other BRCA genes by NGS strategies in non-BRCA1/2 patients. Another research project is focused on oxidative stress and DNA repair: mostly focused on ATM role in both processes (although the strategy is not clearly explained, the in-unit collaboration with team 3 will be of great help). Altogether, this research permits this team to publish their data in good quality journals such as Cancer Research, Blood, JCO, Human Mutation... The field is challenging and competitive and the team is doing well. The scientific outputs are excellent given the fact that the team has been working "full speed" on breast cancer only recently.

The committee has unanimously praised both the quality and interest of this team, more particularly the very high potency of translational research.

Assessment of the unit's academic reputation and appeal

The team is clearly among the national leaders in the field of inherited breast cancer. International scientific reputation is very good for MH Stern, excellent for another team member. The team has attractiveness due to the Curie Institute and scientific environment. Members of the team have interesting collaborations (i.e. Reis-Filho's NGS study published in J Pathol 2012) , they are regularly invited to national and international meetings and are members of french scientific committees, both from INSERM and from charities (Ligue contre le Cancer, ARC...). The team is relatively well funded, for example from ARC (fixe) or INCa (translationnel). Similarly to other teams of this research unit (besides Team1), this group has not yet attracted experienced researchers or recruited young scientists with a permanent position from a french governemental agency or from the University.

Assessment of the unit's interaction with the social, economic and cultural environment

The team has deposited a European Patent on "the methods for detecting inactivation of the homologous recombination pathway (BRCA1/2) in human tumors.

Assessment of the unit's organisation and life

The team leader is highly involved in helping the career development of students and post-docs working with him : the PhD students obtained a high-impact first author publication (Cancer Res, Blood...) for their work in the team. The scientific and personal leadership of the team leader was unanimously praised by all members of his team. However, due to the underrepresentation of senior scientists in his team, the team leader is alone to train and supervise students and post-docs.

Assessment of the unit's involvement in training through research

The group has housed 13 Master students (6 M2) and 5 PhD students (2 in process) since 2007. The committee has praised that most of the PhD students and post-docs obtained a high-impact first author publication for their work in the team. The members of this team are highly involved in L1 (Pharmacy), M1, M2, DIU and DU (Medicine) courses.

Assessment of the five-year plan and strategy

In the next years, the team leader wants to pursue his activity on the molecular and cellular characterization of hereditary breast cancers. He also wants to pursue the research project on the oxidative stress and DNA repair; mostly focused on ATM role in both processes. A program on uveal melanoma could lead to interesting developments.

The projects are adapted to the team task-force, they are highly translational due to interaction with the Curie Institute and the presence of diagnostic laboratories dedicated to breast cancer. The "niche" of hereditary breast cancer remains to be explored and the team has good projects.

In-unit collaborations can be easily developed (i.e. with Team 3 on DNA repair or oxidative stress, and with Team 2 platforms).

In this rapidly moving field, designing plans for 5 years would be inconsiderate. The committee trusts MH Stern to steer his lab in original scientific zones and to make innovative contributions to this field of research.

Conclusion

 Strengths and opportunities:

-Expertise in hereditary BC at the Curie institute and from internationally-renowned members of the team, -Intelligent proposals and leadership, -Vicinity of platforms (bioinformatics, NGS, pathology expertise, SIRIC's NGS), -Well-defined cohorts of patients and controls (Enigma), -Network (ICGC, French), -In-unit collaboration with team 3, -Clear translation strategy (new score, new techniques…), -Curie success in funds raising (equipex, SIRIC…).

 Weaknesses and threats:

-BRCAness and non-BRCA1/2 BC are extremely competitive field. They will succeed by focusing on niches, as they have been cleverly doing so far, but fail if doing what everybody else is doing, -Small team with two main areas : descriptive/genomic and functional. The latter may be harder to translate into forefront studies, -Passage to NGS to manage, -Additional permanent scientist would help developing the proposed project. A real strategy of CR/MCF recruitment should be proposed.

 Recommendations:

-The recruitment of a permanent researcher from the CNRS or the Inserm would improve the group efficicency, -Consolidating functional analyses may help in the future.

  quality and outputsThe team directed by Mr Olivier DELATTRE is composed of 27 members including 11 with a permanent position. The research of the team is mainly focused on the genetic determinism and biology of Ewing sarcoma, rhabdoïd tumours and neuroblastoma. Within these fields, the team has yielded, over the last years, seminal contributions such as (i) the identification of the origin of the Ewing cells corresponding to mesenchymal stem or progenitor cells; (ii) the characterization of the genetic risk factors associated to Ewing sarcoma in population from European origin; (iii) the identification of somatic and germline mutations of the ALK gene in neuroblastoma. The scientific importance of these contributions is highlighted by publications in the top journals such as 2 articles in Cancer Cell, 2 in Nature Genetics, 1 in Nature plus 7 articles in high impact factor journals, such as Journal of Clinical Oncology, Cancer Research and Clinical Cancer Research.

  Other professors (PREM, ECC, etc.) N5: Other EPST or EPIC researchers(DREM, Postdoctoral students, visitors, etc.)

  16 st 2013, at 6 PM Specific premises visited: INSERM U830, Institut Curie, ParisConduct or programme of visit: Wednesday, January 15 st 2013 13:30 Welcome (closed-door) Visiting committee with the AERES Scientific advisor 13:45 AERES representative: the role and procedures of AERES 14:00 Director of the Unit (30' presentation, 30' discussion) : Presentation of the past activities Ms Fatima MECHTA-GRIGORIOU (30' Talk + 30' discussion, including 5' only with the team leader) 9:30 Team 4 -Mr Marc-Henri STERN (30' Talk + 30' discussion, including 5' only with the team leader) representatives of the Institut Curie and Université Paris Descartes 14:45 Discussion with the head of the Unit (if necessary) 15:15 Private meeting of the visiting committee (in presence of the AERES scientific advisor)

Number as at 30/06/2012 Number as at 01/01/2014

	2
				2014-2018
				Number of
				project producers
	N1: Permanent professors and similar positions	5 (3 at 50%; 2 at 30%)	4 at 30%) (2 at 50%; 2	4
	N2: Permanent researchers from Institutions and similar positions	6	6		6
	N3: Other permanent staff (without research duties)	11	11		11
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.)
	N6: Other contractual staff (without research duties)
	TOTAL N1 to N6	22	21		21
	Percentage of producers		100,00%
	Unit workforce	Number as at 30/06/2012	Number as at 01/01/2014
	Doctoral students	11		6
	Theses defended	16		8
	Postdoctoral students having spent at least 12 months in the unit*	7		4
	Number of Research Supervisor Qualifications (HDR) taken	6		7
	Qualified research supervisors (with an HDR) or similar positions	6		7

 Assessment of the unit Strengths and opportunities 1.

Genetics and Biology of Cancers, Institut Curie/INSERM/Université Paris-Descartes/CNRS, Mr Olivier DELATTRE

 Statistics by field: SVE on 10/06/2013

 Supervising bodies' general comments


President Michel Cosnard

Bruno Antonny

This report is the sole result of the unit's 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 PRESENTATION

INTRODUCTION HISTORY AND GEOGRAPHICAL LOCATION OF THE UNIT

A few years ago, the Research Center of the Institut Curie, in coordination with CNRS and Inserm, decided to foster interactions between biologists and chemists by building a new research unit on the topics of chemical biology. This field of research has been very creative worldwide over the last decade and it was rationale for a research institute of such size and ambition as Curie, with a long tradition in trans-disciplinary studies, to make this choice. This project started in 2014 with two teams in biology around Ludger Johannes and Christophe Lamaze direction and one team in chemistry with Frédéric Schmidt, all from Curie. In 2015, Raphael Rodriguez joined the unit to start a junior group. The resulting new unit is one of the 12 research entities of the research center of the Institut Curie, which are grouped according to four domains. This unit belongs to domain 4 'Multiscale Physics-Biology-Chemistry and cancer', with which a Labex is associated.

The unit occupies space in two separate buildings (bâtiment Burg / bâtiment Rossignol, respectively), which are at walking distance. Information was given during the visit about future plans to optimize the limited space allocated to the unit both in terms of experimental benches and offices.

MANAGEMENT TEAM

Mr Ludger Johannes has been heading this unit since its creation in 2014. He will remain the director for the next term, but will team up with Mr Christophe Lamaze, another group leader, as deputy director.

HCERES NOMENCLATURE

SVE2_3; ST4_4.

SCIENTIFIC DOMAIN

Wider than pharmacology or medicinal chemistry, chemical biology consists in designing and developing chemical tools, and using them to better unravel the functioning of biological systems, should it be an organism, a cell, or a biochemical reaction, and without the need or the aim of an immediate medical application. In the case of this unit, chemical biology has been used to study various processes that occur in biological membranes, including signal transduction, cell response to mechanical stress, and membrane traffic. The arrival of the Rodriguez team has expanded the expertise of the unit to the field of cancer biology. To better acknowledge this change, the previous unit's name 'chemical biology of membranes' will change to 'cellular and chemical biology'. A more detailed list of the research lines is as follows:



glycosphingolipid functions in endocytosis and intracellular sorting;  caveolae in mechanoprotection, signaling and transduction;  intracellular signalling from endosomes;  small molecule lead discovery in membrane trafficking, signal transduction and epigenetics;  targeted delivery of therapeutic compounds to tumors and to dendritic cells for immunotherapy;  identification of chromatin binding sites of chemical compounds (click-seq) and therapeutic principles for personalized medicine.

UNIT WORKFORCE

Unit workforce

GLOBAL ASSESSMENT OF THE UNIT

This evaluation covers the first years of this research unit, which was created in 2014 following a previous very positive evaluation by the AERES. Some of the current team leaders were already well established scientists in different research units of Curie. Thus, rather than a pure de novo creation, this unit initially corresponded to a strong reorganisation within the Curie Research Center to promote the interface between chemistry and biology. These historical teams have continued their outstanding work in the field of membrane biology, membrane signalling and inventive chemical biology. In addition, they have succeeded in attracting a remarkable junior team with a strong chemical biology expertise. Thanks to these efforts, the unit has reached both a critical mass and level of quality that allow its recognition at the best international standards. The publication record, as before, covers a large spectrum, from the best general journals (Nature, Science and Cell) to some more specialized but highly recognized journals in chemistry and cell biology. The quality spreads over all teams, which are also very active in translational activities and in training through research. In conclusion, these years of reorganization and creation have been rewarded by success and have led to an exceptional unit. The strategy for the next years consists in (i) attracting a new junior group in the field of chemical biology; (ii) keeping the expertise in chemistry despite the mobility and retirement of several engineers and researchers in this field; (iii) fostering a creative, ambitious and collaborative environment between students, post-docs and all personnel with different expertise both across the teams of the unit and beyond (Curie Research Center and others initiatives in the Paris area); (iv) optimizing lab space.

The evaluation reports of Hceres are available online: www.hceres.com

Evaluation of clusters of higher education and research institutions Evaluation of higher education and research institutions Evaluation of research Evaluation of doctoral schools Evaluation of programmes Evaluation abroad


Grading

Once the visits for the 2012-2013 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 six criteria defined by the AERES. NN (not-scored) attached to a criteria indicate that this one was not applicable to the particular case of this research unit or this team. Criterion 1 -C1: Scientific outputs and quality; Criterion 2 -C2: Academic reputation and appeal; Criterion 3 -C3: Interactions with the social, economic and cultural environment; Criterion 4 -C4: Organisation and life of the institution (or of the team); Criterion 5 -C5: Involvement in training through research; Criterion 6 -C6: Strategy and five-year plan.

With respect to this score, the research unit concerned by this report and its in-house teams the following grades:  Grading table of the unit: Chimie Biologique des Membranes et Ciblage Thérapeutique C1 C2 C3 C4 C5 C6

This project involves two teams in biology and one team in chemistry from two distinct units of the Institut Curie, Paris. The staff of this new unit (7 permanent researchers and 5 permanent staff without research duties) is from Institut Curie, INSERM or CoNRS. The biologists, around Mr LUDGER JOHANNES and Mr Christophe LAMAZE, are part of the UMR 144 (director Mr Bruno GOUD), a leading laboratory in cell biology at the Institut Curie. They have been studying various aspect of cell endocytosis with a specific interest in new mechanisms of membrane deformation, cargo uptake and membrane mechanics. The chemists are from the UMR 176 (current director Mr Jean-Claude FLORENT), a unit with a strong expertise and history in organic chemistry for the synthesis of new bioactive molecules. By anticipating changes in the former UMR 176 with the retirement and move of several principal investigators, they propose to team up around Mr Frédéric SCHMIDT to form a group complementary to the aforementioned biologists. Overall and with the expected recruitment of a new principal investigator in chemistry, the unit should include four principal investigators and ambitions to become an important center in chemical biology. The biologists and chemists have already collaborated, especially during the last years. They will remain in their separated buildings (Bâtiment Burg / bâtiment Rossignol, respectively), which are within walking distance. Some adjustments have been scheduled to improve space use.

The main aim of the project is to foster new research and applications based on recent progress in membrane biology, notably the identification of new portals of entry into the cells by Teams 1 and 2. Improving the cellular uptake of therapeutic molecules depends on a better understanding of biological membranes. Conversely, the various mechanisms by which cells capture molecules or pathogens are inspiring for the discovery of novel drug delivery routes and probe design. Overall the project fits with the tradition of the Institut Curie to conduct basic, translational and clinical research thanks to the combination of researchers from different fields.

Management team

Mr Ludger JOHANNES, INSERM, will head the new research unit. The operational committee will include Team 2 and Team 3 leaders. 2  Assessment of the unit

AERES nomenclature

Strengths and opportunities

Within the Institut Curie, two teams in biology have unraveled new mechanisms for cell entry using bacteria toxins and viruses and clarified the roles of small membranes structures named caveolae at the plasma membrane. Beside their importance in basic research, these remarkable pieces of work suggest interesting and innovative strategies for drug delivery and are inspiring for new approaches in which chemistry helps to understand biological processes (hence the name 'chemical biology'). Of note, this work has already been at the root of collaborations between chemists and biologists and of two startup companies. Chemists at the Institut Curie have had a strong interest in translational research for years, hence the idea of setting up of a single "unité de recherche" entitled "Chimie Biologique des Membranes et Ciblage Thérapeutique" in which chemists and biologists work in synergy.

The excellence of the research, the overall adhesion of the people to the project, the fair self-evaluation (the committee appreciated the SWOT analysis), and the support by the Institut Curie, INSERM and CNRS give firm grounds to the project.

Weaknesses and threats

Balance. Because of the strong history of the chemists as an independent research unit, the main risk is an unbalanced association in which chemistry is 'used' by biology but not the other way around. The main investigators are aware of this risk. Moreover, the committee thinks that the biological processes studied by Teams 1 and 2 should be inspiring for chemists and help them to create new molecules that may have broader interest, extending beyond their application. Indeed, one can notice that the biological structures studied by Team 1 and Team 2 urgently need better chemical description: caveolae and toxin-induced invaginations are intriguing from a chemical point of view because of their bilayer asymmetry, curvature, and unique protein structures (e.g. pentamers, hairpins). Probes adapted to these unique anisotropic environments will be welcome by the community. Since the risk that one field develops at the expense of the other is well understood by the main investigators, this risk is likely to be transcended by the new concepts and ideas that will be born from the association.

Location. Chemists and biologists will remain separated (but within walking distance). However, previous collaborative work between researchers of different fields has been very successful at the Institut Curie. Therefore and despite this physical separation, the environment seems well adapted for the creation of a chemical biology unit.

Interdependence. On a day-to-day basis, collaborative work at the interface between two fields is not easy to organize because progress is not necessarily in phase: for example, the time required for the design and synthesis of a new molecule does not necessarily match the bench work and/or interest of the biologist and vice versa. This interdependence has to be minimized especially during thesis works. Therefore, PIs have to check that, apart from the interfacial aspect of each project, there should be enough scientific work that can be conducted in an independent manner.

Competition. The committee noticed a potential overlap between one research line (cross-presentation) and works carried out by other teams in the Institut Curie. This point was recognized by the researchers and could also represent an opportunity for the sharing of expertise.

Recommendations

General. Biologists and chemists should continue their efforts to work together as this has already led to unique discoveries and applications.

The role of chemistry. From the mechanisms and structures studied by the biologists, chemists should identify issues that are associated with innovative synthesis or chemical strategies, not necessarily linked to immediate relevance in biology. In turn, biologists should make some routine systems or preparations available to chemists to help the development of innovative molecules. Put differently, the committee understands that part of the chemistry needed for vectorization (such as protein-drug coupling) is not necessarily innovative and cannot stimulate per se experts in chemistry. However, the committee considers that the mechanisms studied by the biologists are original (e.g. glycolipid clustering, membrane bending, membrane tension) and should inspire chemists. Biological membranes suffer from naïve and dubious descriptions because of the lack of expertise in chemistry of most biologists. The association between chemists and biologists is therefore very relevant in the field of biological membranes.

Training courses and continuing education. The majority of PhD students, post-docs as well as the main investigators from the two fields are positive about their future association. Special care should be taken, notably through training courses (e.g. those organized by the CNRS and INSERM) and shared lab meetings to make all technicians and engineers part of this challenging project. Considering that institutions generally encourage continuing education, the creation of a chemical biology unit should provide new opportunities for the technicians to develop their careers.

Interdependence. For works at the interface between chemistry and biology, the unit/teams should minimize time mismatch and try to keep some works that can be valued through specialized publications, besides major publications of general impact.

 Detailed assessments Assessment of scientific quality and outputs

The research conducted by Team 1 and 2 leaders is extremely innovative. Their landmark works were published in the most prestigious journals (Shiga-induced endocytosis in Nature, membrane fission in Cell, caveolae as membrane tension sensors in Cell) and resulted in world-wide attention and recognition, as witnessed for example by (1) invitations in the best international conferences (e.g. ASCB, EMBO, Gordon), (2) invitations to write reviews in the best journals (1 x Trends in Cell Biology, 2 x Cell), (3) an election as an EMBO member (L Johannes). There are not many teams in the world with such a high level in membrane biology. Despite a less international exposure, the chemists around Team 3 leader are well recognized at the national level. Moreover, and this aspect is noticeable in the context of the unit creation, they have been collaborating in a very fruitful manner with the biologist teams for many years, notably on chemistry-based protein modification strategy for endocytic pathway leading to one of the aforementioned publications (Nature) but also to articles in Angew Chem Int Ed Engl (1) and ChemMedChem (1).

Assessment of the unit's academic reputation and appeal

All teams attract students, post-docs from France and other countries and are well funded by institutional and industrial funds (ANR, INCa, ). Team 1 leader was recently elected EMBO member, a prestigious academia in Europe. Two talented young researchers were hired as researchers.

Assessment of the unit's interaction with the social, economic and cultural environment

The committee did not notice any weakness on this point. This is remarkable because excellence in basic research does not necessarily imply strong involvement in other aspects of scientific life. Among the most noticeable points: 1) Translational research is highly developed (up to the creation of two start-up companies). 2) Researchers support an important chemical library accessible to the community. 3) Teaching is frequent despite the fact that the unit is not associated with a university (two PIs teach about 40 to 60 hrs/year and are involved in courses organization). 4) Researchers are highly involved in international and national committees or jury work (NSF, ERC, ANR, AERES, CNRS and INSERM sections, INSA, Collège de France, Ligue contre le cancer), in journal editorial boards (Plos One, Amer. J. of Physiol., Traffic,...) as well as in scholarly associations (Société de Chimie Thérapeutique, Société Française de Chimie, Fédération Réaumur, Club Endo Exo…).

Assessment of the unit's organisation and life

The new Unit will be quite small, hence facilitating governance. In addition, Team 1 leader and Team 2 leader (who was formerly Team 1 co-leader) have already shown their ability to combine their strengths in a successful manner. Lab meetings and retreats are scheduled. Resources will be shared. One PhD students has Team 1 and Team 3 leaders as co-supervisors. These two later facts are very positive signs of collective ambitions.

Assessment of the unit's involvement in training through research

With 6 thesis defenses in the current biology teams (5 affiliated to the Ecoles doctorales ED 419 Signaling and Integrated Networks in Biology of Paris 11 University, 1 to the ED 474 "Interdisciplinaire Européenne Frontières du Vivant" of the PRES Sorbonne Paris Cité (Paris 5 and 7 Universities) and 6 thesis defenses in the chemistry unit (5 affiliated to the ED 436 "Médicament, Toxicologie, Chimie, Environnement" of Paris 5 University and 1 to the ED 388 "Chimie physique et chimie analytique de Paris Centre" of Paris 6 University), there is a good tradition of training through research on both sides. All the PhD students were further followed by thesis committees that met every 18 months. Moreover, they have all the possibility to attend conferences for presenting their work. In addition, the PIs give lectures in national and international courses and seem very active in teaching, notably in the Paris area.

Assessment of the five-year plan and strategy

The creation of the Unit anticipates changes in human resources in the former chemistry Team 3 (moves and retirements). To capitalize the expertise of this team in medicinal chemistry and to stimulate new lines of research, the idea is to gather within a single research unit both chemists of this former group around the next Team leader and biologists around Team 1 and 2 leaders. These scientists have shown great interest and success in translational research, notably in chemical biology, beyond their outstanding works in cell biology.

The creation of the unit will not be in phase with the setting-up of a single new location for all research groups. Instead, the researchers will remain in their current lab and workspaces, although some short-term changes are proposed to mix part of the biologists and chemists in shared spaces and to improve the size of existing bench rooms. Large scale operations involving not only the Institut Curie but also universities and engineering schools/higher training institutions within and outside Paris will determine the various possibilities for a unique lab space. Therefore, the creation of this research unit anticipates changes in the area of Paris, where space is seldom. Delays for these interdependent operations are difficult to anticipate and are unlikely to lead to rapid changes within the next two years.

Overall, the strategy seems both rational and ambitious: to target well defined opportunities suggested by new research lines and successful and talented PIs to build, despite uncertainties linked to other operations at a larger scale, something new within an Institute where collaborations across different fields are a tradition. -

In 2007, they showed that membrane deformation during Shiga-toxin uptake, which occurs independently of clathrin, takes of the clustering of glycolipids in the outer leaflet of the membrane. Membrane deformation is thus imposed by the cargo from the outside of the cell and not by a cytosolic 'coat' protein from the inside. In 2010, they demonstrated a similar mechanism for the uptake of SV40 virus in collaboration with A HELENIUS (Zurich). These new mechanisms of cell entry are probably not limited to cell invasion by pathogens. Rather, they might illuminate more general endocytotic pathways, which are functionally very important although their molecular basis has remained obscure. A recent work on an endogenous extracellular lectin (galectin-3) that can mediate glycolipids clustering for its own uptake supports this hypothesis.

-After having studied membrane deformation, the group moved to membrane fission and described in 2010 a novel mechanism of dynamin-independent membrane scission via the involvement of actin and line tension. This work highlights the excellent internal collaborations in the Institut Curie between biologists and physicists.

-Recently, they published a remarkable article on caveolae that challenges the classical view on the function of those small structures decorating the plasma membrane (see report on Team 2).

Not only are the aforementioned studies important for our understanding of cellular membranes but also they trigger new lines of research with important biomedical implications. Thus, the group has performed two noticeable studies in this area, including:

-A high-throughput screening to identify small molecule inhibitors that protect cells from ricin and Shiga-like toxins -Novel Shiga-toxin derived adjuvants for the induction of specific T cell responses as vaccine development.

Assessment of the team's academic reputation and appeal

The work from the team has been internationally recognized at the highest level. Team 1 leader has been invited to 35 conferences during the period of 2007 to 2012 including prestigious events such as Gordon conferences, EMBO, ASCB, FASEB, Naito etc... He has lectured during the same time period at 39 leading international research institutions, such as the ETHZ, Yale, the NIH, just to name a few. He has himself organized a number of important conferences, like the EMBO endocytosis meeting. His achievements have been recognized through the election as EMBO member and through an INSERM-clinical interface contract.

Team 1 leader has been heavily involved in the evaluation of research through committee work in CoNRS/INSERM recruitment/evaluation commission (INSERM CSS3, CoNRS 23). Further, he has worked on editorial boards of leading journals, as editors and as referees for leading journals and agencies. He has also participated in AERES evaluation committees.

Last, numerous collaborations exist with excellent groups in the Institut Curie, in France and within the world and two chargés de recherche have been hired over the last years. The group is well funded by grants from national and international organization (ANR, HFSP…). The excellent reputation and appeal of Team 1 leader is further indicated by his direct supervision of 6 post-docs, most coming from abroad.

Assessment of the team's interaction with the social, economic and cultural environment

Team 1 leader has established two companies during the recent years. This has been possible through the filing of 7 patents and has created several jobs in France and in other countries. The products developed in these companies are promising for cancer therapy and clinical trials for the treatment of breast cancer are underway. Furthermore, the group is member of the LabEx CellTisPhyBio.

Assessment of the team's organisation and life

The former team (1 & 2) has an excellent organization bringing together scientists from different fields of expertise, including staff with medical background. Lab meetings are held regularly, progress is discussed continuously. Team leader and co-leader have previously worked in very synergistic manner.

Assessment of the team's involvement in training through research

The team belongs to the Ecole Doctorale ED 419 Signaling and Integrated Networks in Biology of Paris 11 University. Of the 11 PhD students, which have been trained by the former team, Team 1 leader has supervised 5 PhD students (3 have defended), 3 from foreign countries (USA, India, Germany). One of these 3 PhD students was further affiliated to the ED 474 "Interdisciplinaire Européenne Frontières du Vivant" of the PRES Sorbonne Paris Cité (Paris 5 and 7 Universities). For those of them who already defended, they had a very strong scientific output and went on to a successful scientific career (in companies or as post-docs in excellent labs in France or abroad: EU-openscreen, Biozentrum, Columbia).

The Team head has been involved in teaching/organizing events and courses at the national and international level for a very substantial amount of time (> 40 hrs/yr).

Assessment of the five-year plan and strategy

Given previous successes, the proposed directions make a lot of sense. There is a good balance between risky lines and continuation of previous works. Trying to dissect the code between extracellular cargoes and glycosphingolipids for their mutual interaction is very challenging but the team seems to have the shoulders for such a large scale project. Antigen cross-presentation is fascinating process whose molecular basis is poorly understood; the role of domain boundary forces in this mechanism is an interesting and original hypothesis. Last, deciphering the molecular machineries involved in early endosomes to TGN transport should interest many experts in membrane traffic.

Conclusion  Strengths and opportunities:

Almost all previous findings of the lab contribute to strengths and opportunities as they are quite unique and suggest new lines of research and applications. To quote a few, the recent finding that extracellular galectins (an endogenous exocytosed ligand) follow the same general mechanism of cell entry as Shiga Toxin, suggests that the mechanisms previously uncovered by the team have a broad implication, i.e. there are not limited to the 'exotic' case of a few toxins.

 Weaknesses and threats:

There exist so many lipids and notably glycosphingolipids in the external leaflet of the cell that uncovering the 'carbohydrate code' is very challenging. However, the committee thinks that the team has the shoulder to address this large issue, notably in this new 'chemical biology' unit.

Another very challenging but exciting issue is protein translocation across endosomal membranes.

 Recommendations:

The group is simply encouraged to continue its superb work.

 Detailed assessments Assessment of scientific quality and outputs

The discovery that caveolae act as tension sensors is a breakthrough in cell biology and should have a strong impact in the future. The original work was published in Cell in 2011 and is already cited 30 times. Team 2 leader was co-corresponding author of this paper and then published a review on this topic with his collaborator in physics in one of the best review journal (Trend in Cell Biology). Because of their shape, caveolae have been proposed to be intermediates in endocytic pathways (40 years ago, Simionescu and Palade suggested that they are involved in the trans endothelial transport of Albumin). Instead, this new study demonstrates that caveolae act as mechanosensors at the plasma membrane, serving as membrane reservoirs for cells that experience sudden and acute mechanical stress.

Besides this most important and original study, Team 2 has published papers on other research lines (endocytosis, sterol transport…) and in more specialized journals (1 FASEB J, 1 JBC, 1 PLoS one, 1 FEBS Lett, 1 Cell Microbiol) where the PI is a co-corresponding author. Team 2 leader also contributed to many of the spectacular papers on clathrin-independent endocytosis (e.g. Shiga Toxin) published with Team 1.

Assessment of the team's academic reputation and appeal

The Team 2 leader is well known at the international level for his previous works on clathrin-dependent andindependent endocytosis as well as for the interplay between membrane compartmentalization and signal transduction. His recent finding on caveolae and mechanotransduction should further increase his visibility. During the last 5 years, he was invited to talk in 12 conferences including ASCB, EMBO endocytosis and in well-known universities in Europe and North America. He has organized important national conferences, such as the Fédération Réaumur des Sciences du Vivant or the Exo-Endo Club. The team is well supported by funds from ANR. With 6 post-docs, four from France, two from India, the team is very attractive.

Assessment of the team's interaction with the social, economic and cultural environment

The team leader has strong implication in scientific animation: first in committees for French fundations and agencies (ANR and AERES, INSERM CSS); second as an academic editor for PLoS ONE; last as an organizer of conferences in France (Congrès Réaumur). He also has been a co-founder of the exo/endo club that plays an important role in the field of cell biology in France and he is involved in translational research through a joint programm with the Swiss biotech NovImmune.

Assessment of the team's involvement in training through research

The Team leader is highly involved in training and teaching (about 50 hours/yr), largely above the average for a CNRS or INSERM researcher. The team is affiliated to the Ecole Doctorale ED 419 Signaling and Integrated Networks in Biology of Paris 11 University, and has trained 5 PhD students (3 have defended, all with publications), three from France, one from Germany and one from Poland.

Assessment of the five-year plan and strategy

The committee was impressed by the oral presentation and responses during the discussion. Team 2 leader showed an excellent and fair self-evaluation as well as a deep knowledge of many issues in cell biology. On the one hand, Team 2 leader is aware that his recent finding on caveolae is a turning point and a fantastic opportunity to build something new. On the other hand, he considers that mechanotransduction remains a special field where other expertise is needed and that he has to keep a niche at the crossroads between signal transduction/traffic and caveolae. His relationship with Team leader 1 is very good and constructive and this should help building the new unit.

Conclusion:

 Strengths and opportunities:

As mentioned above, the opportunity is obvious and most exciting: the seminal finding that caveolae act in mechanotransduction should trigger new lines of investigations. The committee also noted that these structures, by their shape, unusual lipid composition, original protein topologies (e.g. amphiphilic character of caveolin) are interesting from the physicochemical point of view and could be inspiring for the chemists to build specific probes that may help to follow membrane tension. This fits well with the objectives of the new unit.

 Weaknesses and threats:

The team will have to balance the efforts between what is new (caveolae and mechanotransduction) and the more classical lines of research (traffic and signal transduction) in a small team with only one tenure researcher.

 Recommendations:

The committee simply advises the team to continue its effort on caveolae and to discuss opportunities with chemists to probe caveolae local environment as a function of mechanical stress. Of course, securing some positions will help to give stable grounds to the team.

 Detailed assessments

Assessment of scientific quality and outputs Team 3 has a very good track record of publications (39) within the period of evaluation. Some papers were published in top journals (2 Angew Chem, 2 Cancer Res, 5 J Org Chem, 2 Faseb, 1 Nature). The most prestigious publications were generally the results of collaborative studies with biologists from the Curie Institute. As such, the chemists did not always appear as the principal authors in several important publications.

Among the milestones of the last years, three lines of research at the interface between chemistry and biology should be highlighted: (1) Vectorization based on Shiga Toxin of antitumor compounds and contrast agents. These works are associated to proofs of concept for a topo-isomerase inhibitor and for apoptotic drugs. (2) Chemical Biology: biological molecules have been modified and the chemical library of the Curie Institute has been developed leading to the discovery of inhibitors for syndecan-1 and protein kinase CK2. (3) Chemistry: the team has successfully developed self-immolative spacers in which a drug and a probe can be released with predictable and tunable rates.

Assessment of the team's academic reputation and appeal

The work of this team fits very well with current issues at the interface between biology and chemistry. The researchers have developed a large network of collaborations in France notably within the Curie Institute. Overall, this has lead to a number of projects supported by the ANR (4), INCA (3), PIC (2) and Innabiosanté. Six post-docs have been hired. International collaborations are more seldom as well as participations/invitations to international events.

Assessment of the team's interaction with the social, economic and cultural environment

The team has been very active in technology development and transfer with 6 patents (including two licences). The labeling 'Institut Carnot' of the Institut Curie acknowledges these efforts to develop translational research and applications. Some researchers belong to the science advisory boards of companies. Also noticeable is the primary role of the team in the chemical library of the Institut Curie, a very valuable tool for the community. The Team leader is involved in the Société de Chimie Thérapeutique.

Assessment of the team's organisation and life

Given the retirement and moves, this aspect is difficult to assess. However, Team 3 has been very active in setting up the chemical library of the Institut Curie. They have organized lectures, short workshops (journées de la chimie organique et chimie biologique) and an international conference (Rencontre Internationale de Chimie Thérapeutique). Their active collaborations within the Curie Institute show a good integration. This integration is perhaps at the expense of the influence of the team in chemistry: collaborative works with biologists sometimes hide the merits of the chemists. However, this imbalance is a general trend given the growing importance of biology and the fact that many biological issues are inspiring for chemists but can hardly be attacked solely by them.

Assessment of the unit's involvement in training through research

The team belongs mostly to the Ecole Doctorale ED 436 "Médicament, Toxicologie, Chimie, Environnement" of Paris 5 University. With 10 PhD students (6 have defended), all with publications, and with lectures at Master 1 and 2 levels, the team shows a marked involvement in training and teaching. One ongoing PhD student is affiliated to the ED 388 "Chimie physique et chimie analytique de Paris Centre" of Paris 6 University.

Assessment of the five-year plan and strategy

Among the four lines of research, two are extremely innovative: vectorization based on Shiga Toxin and selfimmolative spacers. In both cases the team is in excellent position to develop these topics given its expertise, its previous works and because of the reorganization of the unit with the experts in biology. The challenge will be to keep some independence notably through other projects, which should have been better detailed, and, as such, to balance the merits between the teams in biology and in chemistry. In this respect and as previously detailed in the general comments, the committee thinks that the membrane structures studied by Teams 1 and 2 could be inspiring for probe developments given the fact that these structures have peculiar composition asymmetry, curvature… This new unit in 'chemical biology' is a very good opportunity for the Team's 3 chemists to develop researches at the interface between their field and biology. The reasons are obvious: the excellence of the research, the novelty of the biological mechanisms, their potential impacts in drug design and vectorization, and the ongoing collaborations between the researchers.

 Weaknesses and threats:

The visibility is modest at the international level. The team size decreases as a consequence of moves and retirements. For the moment the partnership with the biologists is chemistry for biology not chemistry with biology.

 Recommendations:

On a short term basis, the team should put the emphasis on what has been successful with the biologists over the last years.

On a long term basis, the team should put a great deal of efforts into a deep understanding of the processes studied by the biologists. Despite their complexities, the committee thinks that these mechanisms are sufficiently new to inspire innovative organic chemistry approaches; in brief, the plasma membrane is a puzzle of domains whose dynamics, structure, polarity, mechanics are extremely difficult to study with the current tools.

The team should be more active at the international level (attendance to conferences abroad).

Grades

2 N3:N4:

 2 Permanent professors and similar positions N2: Permanent EPST or EPIC researchers and similar positions 3 2 Other permanent staff (without research duties) 3 [2,3]2 Other professors (PREM, ECC, etc.)N5:Other EPST or EPIC researchers (DREM, Postdoctoral students, visitorsquality and outputsThe Team 1 leader is an internationally recognized leader in the field of endocytosis and membrane trafficking. He has been heading an independent research group focused on clathrin-independent endocytosis since 2001 in the UMR 144 (director B GOUD at the Institut Curie. Throughout his career and particularly during recent years, his scientific output has been remarkable both from a quantitative and qualitative point of view. Team 2 leader contributed to these impressive works.As a whole, the former team (1 & 2) has published 70 original papers between 2007 and 2012 including 4 research papers and 2 reviews in top journals (Nature and Cell). Team leader 1 was corresponding author of one research article in Nature, two research articles in Cell, and two reviews in Cell. Those papers, even the most recent ones, are already highly cited.The former team (1 & 2) has uncovered new molecular mechanisms in membrane trafficking and mechanics:

Conclusion

  Strengths and opportunities:

  Chimie des biomolécules, des sondes, et des inhibiteurs hétérocycliques

	1  Introduction
	C1	C2	C3	C4	C5	C6
	A+	A	A	NN	A+	A+
	C1	C2	C3	C4	C5	C6
	A	B	A	A	A	A

 Grading table of the team:

History and geographical location of the unit

Unit workforce Number as at 30/06/2012 Number as at 01/01/2014

	Unit workforce:
				2014-2018 Number of project producers
	N1: Permanent professors and similar positions
	N2: Permanent researchers from Institutions and similar positions	8	7	7
	N3: Other permanent staff (without research duties)	7 [5,8]	5
	N4: Other professors (Emeritus Professor, on-contract Professor, etc.)
	N5: Other researchers from Institutions (Emeritus Research Director, Postdoctoral students, visitors, etc.)	9	9	1
	N6: Other contractual staff (without research duties)	2	4
	TOTAL N1 to N6	26 [24,8]	25	8
	Percentage of producers	100 %
	SVE1_LS3 (principal); ST4 (secondary) Unit workforce	Number as at 30/

06/2012 Number as at 01/01/2014

	Doctoral students	9
	Theses defended	12
	Postdoctoral students having spent at least 12 months in the unit*	17
	Number of Research Supervisor Qualifications (HDR) taken
	Qualified research supervisors (with an HDR) or similar positions	8

Critères C1 Qualité scientifique et production C2 Rayonnement et attractivité académiques C3 Relations avec l'environnement social, économique et culturel C4 Organisation et vie de l'entité C5 Implication dans la formation par la recherche C6 Stratégie et projet à cinq ans

	A+	67	62	52	73	65	60
	A	57	67	71	45	65	63
	B	12	7	4	7	6	14
	C	0	0	0	3	0	1
	Non Noté	3	3	12	11	3	1
	Percentages
	Critères	C1 Qualité scientifique et production	C2 Rayonnement et attractivité académiques	C3 Relations avec l'environnement social, économique et culturel	C4 Organisation et vie de l'entité	C5 Implication dans la formation par la recherche	C6 Stratégie et projet à cinq ans
	A+	48%	45%	37%	53%	47%	43%
	A	41%	48%	51%	32%	47%	45%
	B	9%	5%	3%	5%	4%	10%
	C	0%	0%	0%	2%	0%	1%
	Non Noté	2%	2%	9%	8%	2%	1%
	Histogram

Chimie Biologique des Membranes et Ciblage Thérapeutique, CBMCT, Institut Curie, CNRS, INSERM, M. Ludger JOHANNES

 Supervising bodies' general comments


President Michel Cosnard

Vincenzo Barone

This report is the sole result of the unit's 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 PRESENTATION

INTRODUCTION HISTORY AND GEOGRAPHICAL LOCATION OF THE UNIT

The institute, located at Chimie ParisTech, will be constituted by 4 teams geographically close to each other (same building), namely the "Catalysis, Synthesis of Biomolecules and Sustainable Development team" (hereafter CSB2D), the "Theoretical Chemistry and Modeling team" (hereafter TCM), the "Inorganic Chemical Biology team" (hereafter ICB) and the "Synthesis, Electrochemistry, Imaging & Analytical Systems for Diagnosis team" (hereafter SEISAD).

MANAGEMENT TEAM

The team will be directed by Mr Carlo ADAMO and assisted by Mr Gilles GASSER.

HCERES NOMENCLATURE

ST4: chemistry.

SCIENTIFIC DOMAIN

The research topics of the future unit will be centred on chemistry for life sciences and health with competences in organic synthesis, computational, analytical and physical chemistry and chemical biology.

UNIT WORKFORCE

GLOBAL ASSESSMENT OF THE UNIT

The proposed unit, named Institute of Chemistry for Life and Health Sciences (i-CLHeS), aims to become a high-performing research institute with high national and international visibility at the interface between Chemistry and Life and Health Sciences. If successful, it will surely widen the visibility and the role of Chimie ParisTech from the already established field of energy and material sciences to life and health sciences. The four teams involved in the project are complementary and of high scientific level and discussions with several team members indicate a convinced sharing of the new ambitious project. As a consequence, all the premises seem to be set for a successful establishment of a competitive unit. It is, of course, impossible at this stage to judge results, but only state that the first objectives are well defined and, provided that the new director, has the possibility to incentive by different means collaborative projects and integration. The previous expertise and high scientific level of the director are strongly reassuring in this connection. The success will rely on specific human (especially administrative and technical) and financial resources which must be gradually devoted to this project.

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From

  2012 to 2014, the CSB2D team was part of the "Charles Friedel Laboratory" (UMR CNRS/ENSCP) created in 2008 and led by Mr A. VESSIERES and V. VIDAL as deputy director. In 2014, the CSB2D team joined a new laboratory led by Mr M. MORTIER called "Institut de Recherche de Chimie Paris" (IRCP) that included 9 others teams. The TCM team was involved, from 2012 to 2014, in the "Laboratoire d'Électrochimie, Chimie des Interfaces et Modélisation pour l'Énergie" (LECIME, UMR CNRS/ENSCP) led by Mr M. CASSIR. Then the team joined the "Institut de Recherche de Chimie Paris" (UMR 8749) at its creation in 2014. The IBC team is a newly-created team founded as "équipe d'accueil" upon the arrival of Mr Gilles GASSER at Chimie ParisTech in october 2016 from the university of Zurich. The SEISAD team was created in 2006 within the unit called "Unité de Pharmacologie Chimique et Génétique et d'Imagerie" (UPCGI, CNRS/INSERM/Chimie ParisTech/université Paris Descartes) directed by Mr Daniel SCHERMAN. This team was located at Chimie ParisTech from that time until now. The present configuration of the team raised in 2011 when Mr Fethi BEDIOUI became the leader and when Ms Anne VARENNE joined the team. In 2014 the unit became "Unité de Technologies Chimiques et Biologiques pour la Santé" (UTCBS), consolidating its present configuration.

  time research directors (Directeurs de recherche) and similar positions 4 3 Full time research associates (Chargés de recherche) and similar positions

HCERES scientific officer: Mr Georges MASSIOT Representatives of supervising institutions and bodies:

	Unit name:	Institute of Chemistry for Life and Health Sciences
	Unit acronym:	i-CLHeS
	Requested label:	UMR
	Application type:	Restructuration
	Current number:	8247
	Head of the unit (2017-2018):	Mr Michel MORTIER
	Project leader (2019-2023):	Mr Carlo ADAMO
	Number of teams or themes: 4
	COMMITTEE MEMBERS
		Mr Erick DUFOURC, Mr Bruno Bujoli, CNRS
		Mr Christian LERMINIAUX, Chimie ParisTech
		Mr Michel TATOULIAN, Chimie ParisTech

Chair:

Mr Vincenzo BARONE, SNS, Italy Experts: Mr Valentine ANANIKOV, Russian Academy of Sciences, Russia Mr Jean-François HALET, CNRS, université de Rennes 1 Mr Emmanuel MAGNIER, CNRS, université de Versailles Saint-Quentin (representative of CoNRS) Mr Michel PERDICAKIS, CNRS, université de Lorraine (supporting personnel) Ms Sabine SZUNERITS, université de Lille (representative of CNU)


President Michel Cosnard

Bernard Ducommun

This report is the sole result of the unit's 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 PRESENTATION

INTRODUCTION HISTORY AND GEOGRAPHICAL LOCATION OF THE UNIT

The UMR 144 "Subcellular structure and cellular dynamics" was created in 1995 as a joint research unit with Institut Curie, CNRS and University Pierre et Marie Curie (UPMC U Paris 6). It was renewed on January 1 st , 1999, 2003, 2007, and 2011. It is located 12 rue Lhomond in Bâtiment Lhomond, which is one of the Institut Curie research buildings on the montagne Ste Geneviève in the close vicinity of the Curie Hospital.

MANAGEMENT TEAM

The current director is Bruno GOUD (DRCE, CNRS). From January 2019 Franck PEREZ (DR1, CNRS) will head the unit assisted by a deputy director Renata BASTO (DR2, CNRS).

HCERES NOMENCLATURE

SVE_1, SVE2_2, SVE2_3.

SCIENTIFIC DOMAIN

The 14 teams currently hosted at the UMR 144 are conducting research that covers various aspects of cell biology and cancer cell biology, including intracellular transport, cytoskeletal dynamics, cell division and migration, cell differentiation, morphogenesis, and cell signaling. The general scientific objective of these teams is to understand the biogenesis of cell compartments, the molecular mechanisms that control normal cell functions and their dysregulation, in particular in cancerogenesis.

The unit is part of the scientific domain entitled "Multiscale physics-biology-chemistry and cancer" of the Curie Institute, together with two other units: UMR 168 (Maxime Dahan) and UMR 366 (Ludger Johannes), that has been organized to facilitate and strenghten robust scientific interactions between the teams. The UMR 144 is also part of the Laboratory d'Excellence (LABEX) CelTisPhyBio coordinated by B. Goud and M. Dahan.

With the aim to clarify the scientific identity, the management proposes to rename the research unit as: Cell Biology and Cancer".

UNIT WORKFORCE

GLOBAL ASSESSMENT OF THE UNIT

The UMR 144 is an outstanding unit where modern cutting-edge cell biology is conducted with brio. With a remarkable interdisciplinary panel of specialists, the unit carries out highly original research at the forefront of their fields.

The excellence of the recent recruits and the internationally recognized outstanding quality of the established groups, together with a remarkable technological environment (imaging and antibody core facilities) make the UMR 144 a very attractive and unique place with high national and international visibility.

The unit is very successful in attracting grants from major French and international funding agencies, and funding from industrial bodies. Two groups received an ERC starting grant, one an ERC consolidator and one an ERC advanced grant.

UMR 144 has an exceptional scientific production with 370 publications, one third in journals with impact factors above 9 (Nature Cell Biol., Science, Cell rep., Nature Commun, Curr Biol., PNAS, Sci. Transl. Med.). The Unit has a major international reputation and is attractive for students and post-docs.

The future research plan and strategy are outstanding, with all the ingredients to succeed in producing results and publications of major impact.

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Unit workforce Number 30/06/2017 Number 01/01/2019 Permanent staff

	Full professors and similar positions Assistant professors and similar positions Full time research directors (Directeurs de recherche) and similar positions Full time research associates (Chargés de recherche) and similar positions Other scientists ("Conservateurs, cadres scientifiques des EPIC, fondations, industries, etc.") High school teachers Supporting personnel (ITAs, BIATSSs and others, notably of EPICs) Non-permanent staff Non-permanent professors and associate professors, including emeritus Non-permanent full time scientists, including emeritus, post-docs Non-permanent supporting personnel PhD Students TOTAL non-permanent staff 27 TOTAL permanent staff 2 1 14 15 0 0 59 0 38 22 39 99 TOTAL unit 158	2 1 14 15 0 0 65

Representatives of supervising institutions and bodies:

Ms Geneviève ALMOUZNI, Institut Curie Mr Hervé MOREAU, CNRS Ms Frédérique PERRONNET, Université Pierre et Marie Curie Compartimentation et dynamique cellulaires, CDC, Inst Curie, CNRS, U Paris 6, Mr Bruno GOUD, Mr Franck PEREZ


President Michel Cosnard

Xavier Vekemans

Ms Myriam Valéro

Mr Xavier Vekemans

Debashish Mr

Bhattacharya

Dominique Mr

De Vienne

Mr Xavier Nesme

Ms Carole Smadja

Steven Mr

Ball

Ms Martine Hossaert

INTRODUCTION HISTORY AND GEOGRAPHICAL LOCATION OF THE UNIT

The UMI 3614 laboratory of Evolutionary Biology and Ecology of Algae (EBEA) was created in 2014 with five hosting institutions: CNRS and UPMC in France, and PUC and UACh in Chile. In France, the UMI is one of the units of the SBR. This international laboratory is spread across three distinct sites: Roscoff (France), Santiago and Valdivia (Chile).

The scientific collaboration between members of the French and Chilean teams dates back to the 1990s, but administratively the joint laboratory started in 2003 with the creation of an international associated laboratory between SBR and PUC.

MANAGEMENT TEAM

The management team is composed of the unit director, Ms Myriam VALÉRO (France), and the deputy director, Mr Sylvain FAUGERON (Chile).

HCERES NOMENCLATURE

SVE1_2.

SCIENTIFIC DOMAIN

The UMI 3614 research activities address the fields of evolutionary biology, ecology, and conservation biology with a specific focus on marine "algae" organisms (in a broad sense) including both unicellular ("microalgae") and multicellular ("seaweed") taxa. These scientific activities combine fundamental research objectives in relation to the study of biodiversity tackled with theoretical, empirical, and experimental approaches as well as applied research goals in relation to the exploitation of algal bioresources.

UNIT WORKFORCE

Unit

GLOBAL ASSESSMENT OF THE UNIT

The research activities of the unit are of high quality and tackle three important topics in evolutionary ecology with distinct methodological approaches while sharing a common set of original biological models (micro and macro-algae). Such biological models have remained poorly investigated taxonomically and ecologically, although they possess some very interesting evolutionary properties such as alternation of autonomous haploid and diploid phases and/or within species co-occurrence of sexual and asexual reproduction, and have sometimes important ecological functions.

The unit is taking strong benefit from its international status which allows a relevant combination of expertise, excellent opportunities to access to natural populations of distinct biological models with complementary properties, large access to a wide diversity of funding sources, and synergistic scientific interactions between sites. In addition, unit members have an excellent dynamics for student training, fund raising, international collaborations, outreach activities, and for developing high profile international research in Chile.

The main weakness could lay in the unit involvement in too many questions on too many model species, taking into account the personal resources of the Unit. However, the knowledge and expertise about numerous biological models coupled with new technologies, some of which are currently set up in the unit, are a driving force that will generate novel findings and create new research directions.

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  personnel (ITAs, BIATSSs and others, notably of EPICs) 5


President Michel Cosnard

John Stein

This report is the sole result of the unit's 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 PRESENTATION

Unit name:

Physiopathology of vision and binocular motor control

MANAGEMENT TEAM

The director of the IRIS team is Ms Zoï KAPOULA, a CNRS research director. She is the proposed director for the future laboratory.

HCERES NOMENCLATURE SVE4 Neurosciences

SCIENTIFIC DOMAIN

The IRIS Team is a small team, but with a very focused research theme dealing with every aspect of binocular eye movement control from its basic neurophysiology, through its interactions with the vestibular system and postural control, to clinical and cultural applications.

UNIT WORKFORCE

GLOBAL ASSESSMENT OF THE UNIT

The IRIS team is unique in both Europe and Internationally in studying every aspect of binocular eye movement control from its basic neurophysiology, through its interactions with the vestibular system and postural control, to not only the effects of its maladjustment on clinical conditions such as dyslexia, but also its influence on cognition and even on aesthetic judgments. Beyond this exceptionally broad range, the most unusual feature and strength of the Team is its extremely effective collaboration with clinicians. The team is a leader in the currently very fashionable field of 'translational medical research', which has culminated in the award of 7 patents which industrial partners should be able to translate into financial benefits as well. The team has also been successful in publishing an impressive number of papers, if we take into account the small size of the team. Many labs pay lip service to translation, but few are as effective in actually benefiting clinical practice as the IRIS team is proving to be. Moreover, the team shows clear strengths as concerns its research and funding as well as its capacity to train doctoral students and attract post-doctoral research scientists. Lastly, the development of tools for both diagnosis and rehabilitation is a major asset of the team. The outline proposals for future studies is ambitious, in particular to exploit the basic research already done, The small size of the Team could be a weakness, but it is counterbalanced by a very high rate of publication and a very strong dynamic from the actual members. Moreover, increased interactions with other research Labs within the Neuroscience Center des Saints-Pères could easily be enhanced with more administrative support. This would be beneficial for everyone and allow sharing platforms and technicians.

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  LOCATION OF THE UNIT Since 2014, the Team IRIS "Physiopathologie de la Vision et de la Motricité Binoculaire" is attached to the Fédération des Neurosciences des Saints-Pères (FR3636) and then affiliated to the Université Paris Descartes, UFR Biomédicale and the CNRS.The IRIS Team is located within The Neuroscience Center des Saints-Pères, 45 Rue Saints-Pères, 75006 Paris.

  personnel (ITAs, BIATSSs and others, notably of EPICs)