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 and was given along with an overall assessment. 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 received the overall assessment and the following grades:  Grading table of the unit: AstroParticule et Cosmologie -APC C1 C2 C3 C4 C5 C6 A+ A+ A A+ A+ A+  Grading table of the team: E1 ADAMIS C1 C2 C3 C4

Management team

The director of the Laboratory is Mr Pierre BINETRUY. He is assisted by two Deputy directors: Mr Sotiris LOUCATOS and Ms Alessandra TONAZZO. Scientists associated with the laboratory belong to at least one of the following teams: (1) ADAMIS (data analysis and computing), headed by Mr Radek STOMPOR; (2) High Energy Astrophysics, headed by Mr Etienne PARIZOT; (3) Cosmology and Gravitation, headed by Mr Yannick GIRAUD-HÉRAUD; (4) Neutrinos, headed by Mr Antoine KOUCHNER; and (5) Theory, headed by Mr David LANGLOIS. Technical and administrative personnel are assigned to technical and administrative departments, respectively. The head of the technical department is Mr Christian OLIVETTO, and the head of the administrative department is Ms Emmanuelle ANCOURT-FOISSAC.

AERES nomenclature

The scientific activities of the laboratory fall under ST2 (Physics) and ST3 (Earth and universe sciences). APC has made very significant contributions to its chosen fields of research. These are detailed in the assessments that follow. In addition the laboratory has established significant ties to industry associated with its major hardware efforts, and a number of staff members have taken on important roles in French public outreach activities. The management of the laboratory is well appreciated by the staff, and morale is generally quite high. Communication both downward and upward is effective through direct channels and through the Laboratory Council.

Unit workforce

Unit workforce

APC is establishing itself as a major center for the support of space experiments among CNRS laboratories. It successfully teamed up with IPGP and AIM on a "labex" proposal called UnivEarthS. In addition, it has taken part in an "equipex" proposal called GRAVITER for the preparation of space missions in fundamental physics and earth and planetary sciences. This latter proposal only made it to the wait list, but it is being considered for the campus extension in Ivry. Finally, the establishment of the Francois Arago Centre (FACe) has provided a unique multi-mission data analysis facility for data storage and processing with direct connectivity to CC-IN2P3. All of these events present promising new opportunities for growth at a national level in space research.

Weaknesses and threats

The Committee identified no major weaknesses in the laboratory. There is a modest threat associated with the fact that the Director will soon step down as Director. He has personally played an enormous role in the establishment of APC and in the guidance of its formative years. He will be very difficult to replace.

APC has developed a very ambitious strategic plan, involving many new projects. If all of these projects come to fruition, the laboratory will be strapped to fulfill all of its desired roles, and some difficult choices will have to be made.

Recommendations

The laboratory should be continued at its present level with modest growth to support its diverse and exciting scientific program.

 Detailed assessments

Assessment of scientific quality and outputs APC has made significant contributions to international particle astrophysics and cosmology research in a number of diverse areas. Particular highlights over the past five years include:

-

The Double CHOOZ experiment provided the first measurement of θ 13 , a major result in particle physics. APC played a leading role in this experiment,

Assessment of the unit's academic reputation and appeal

The laboratory's academic reputation is very strong. Elements that contributed to the establishment and maintenance of that reputation include:

-

The APC-led Double CHOOZ design became the standard for the worldwide reactor neutrino facility, Assessment of the unit's interaction with the social, economic and cultural environment APC has established significant ties to industry associated with its major hardware efforts. In particular the "amont/aval" strategy that the laboratory has developed leads to outsourcing to industry of major fabrications at higher technical readiness levels. This facilitates strong academic/industrial partnerships in some key technical areas.

Several laboratory staff members have taken very significant roles in French public outreach activities in the fields of cosmology and astroparticle physics.

The laboratory has participated in IAEA Vienna studies on neutrino detection for non-proliferation and safeguard activities.

Assessment of the unit's organisation and life

The management of APC is highly appreciated by the staff, and the morale is high. Communication is effective between the various units and with the central administration. The leadership has done a very effective job at anticipating trends in European and French science funding, and taken appropriate steps to ensure that the laboratory is well-positioned as funding patterns evolve.

The APC Technical Division has emerged quickly into a strong service unit supporting the hardware programs of the laboratory. The leadership does a very good job managing the balance between the multiple demands on the engineering groups. Morale is high, although the ratio of technical to scientific staffing levels is lower than optimal. The division has taken steps to establish itself as a major center for space engineering, especially among IN2P3 labs. The TARANIS Project is an excellent testbed for developing relevant experience in this arena.

APC has made excellent progress at integrating the broad disciplines of particle astrophysics and cosmology in a cohesive way across experiment, observation, and theory.

Assessment of the unit's involvement in training through research

The total student and postdoc numbers are appropriate for a laboratory of this size. The mentoring of graduate students is taken seriously, and is applied uniformly throughout the laboratory. The situation is somewhat less clear for postdocs, some of whom do not feel adequately mentored during their brief stays there.

Assessment of the five-year plan and strategy

The laboratory has developed a strategic planning process engaging all staff to plan its future for the next two decades. Strong investments are being made in gravitational wave physics, wide-field survey cosmology, neutrino physics, and multi-messenger high energy astrophysics.

The overall program has many uncertainties, but is ambitious. If all of these projects come to fruition, the laboratory's technical division may find it difficult to fulfill all of the desired roles proposed by the scientific staff.

Through its partnership in UnivEarthS, and the establishment of FACe, APC has positioned itself well to play a strong role in space astrophysics efforts in France in future years. These efforts are strongly supported by CNRS, CNES, CEA, and the University.

A potential new major project that emerged from the strategic planning process is SKA. The laboratory will need to take proactive steps to establish a credible program in this new field. ADAMIS is the smallest scientific group at APC, consisting of 8 permanent research staff, 5 students and 3 postdocs. However, the group has strong connections to Cosmology-Gravitation and High-Energy Astrophysics, as well as to 'Service Informatique' inside APC; in fact, all ADAMIS group members are also members in at least one other group. The "transverse" nature of ADAMIS emphasizes the use of computer science, numerical or statistical techniques to address physics data analysis or simulation topics.

The ADAMIS group has had special success with SMICA (a component separation software package for Planck data) and the Planck Sky Model, whose significance derives from the importance of component separation to the analysis of Planck data. As Planck data and results start going public in the Spring of 2013, the contributions of ADAMIS will become more evident and enhance the profile of APC.

Assessment of the unit's academic reputation and appeal

In accordance with its transverse nature, ADAMIS members publish and are visible in the computer science literature, and maintain significant collaborations outside of the physics community, e,g, with INRIA. They also maintain a good network of collaborators within France, including several alumni of the group (now at LPCE or ECP). All this adds up to substantial academic influence and appeal, as demonstrated by their journal refereeing activities, and their participation on international cross-disciplinary collaborations.

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

While ADAMIS has not found opportunities for technical transfer to non-academia, they do have a strong presence in cultural outreach. For instance, a key member of the group has received the Haute-Maurienne Vanoise 2012 Award for best popular book in astronomy ("Les nouveaux messagers du cosmos"). The group is also active in a variety of public outreach events, and in high school teachers training.

Assessment of the unit's organisation and life

The group is well organized and made a particularly energetic presentation, reflecting an enthusiastic leadership. They have served the APC as a whole well by carrying out effectively the transverse activities in collaboration with Cosmology-Gravitation and High-Energy astrophysics, and by engaging some members of the 'Service Informatique'.

Assessment of the unit's involvement in training through research

The group has produced 5 doctorates in the last 5 years, with 5 more students currently enrolled. The group trained a total of 15 masters students. This is a good record for the modest number of permanent staff (8). ADAMIS staff is quite active in teaching at various levels.

Assessment of the five-year plan and strategy

In terms of strategy and planning, the group's plan reflects the general trends and projects at APC rather than formulating their own scientific trajectory. The ADAMIS strategy seems to center on their ability to respond to scientific opportunities with novel ideas and quick implementation, especially in the data analysis domain, but also in simulations.

Team 2 :

High-Energy Astrophysics (AHE) Name of team leader: Qualified research supervisors (with an HDR) or similar positions 9

 Detailed assessments

Assessment of scientific quality and outputs

The AHE group is a very ambitious and dynamic group, constituting the largest entity in APC with 24 permanent members and 36 PhD students and postdocs over the last five years. It is engaged in many international projects on astroparticle physics with telescopes or instruments detecting photons, cosmic rays or neutrinos. This can be in space with the successfully operating INTEGRAL observatory, and with future space missions such as ASTRO-H, SVOM/ECLAIRs, and JEM-EUSO, or on the ground with HESS, ANTARES, the Pierre Auger Observatory, the X-shooter detector and preparing for CTA and KM3NET.

The group has a leading role in imaging the hard X-ray/soft gamma-ray sky with the delivery of, and analysis of data from the imager IBIS/ISGRI aboard ESA's INTEGRAL. Extremely accurate characterization of the imager response allowed the generation of important results, e.g.: the 3rd and 4th IBIS source catalogues (>700 sources), opening up the non-thermal hard X-ray sky; deep multi-messenger studies of source-crowded regions of the Galactic Plane, most notably the GC region studying the past activity of the central BH; in the IBIS Compton mode the first detection of polarization in gamma-rays from the BH binary Cyg X-1 and a GRB, rendering the most stringent limit on violation of Lorentz invariance. Furthermore, the group was successful in multi-wavelengths and multi-instrument studies of unidentified sources, such as AGN, PWNe and compact binaries. The latter also included observations at TeV energies with HESS. Preparatory studies are made to harvest with HESS II, and the group is involved in scientific and design studies for CTA.

The responsibility for the TARANIS/XGRE flight hardware is recognition of the acquired technical expertise in AHE over the evaluation period and offers an excellent opportunity to manage a complete space system in the APC laboratory.

In neutrino astronomy, the period under evaluation marked the transition from the construction phase to the data exploitation phase of the ANTARES telescope. The group has a strong role with important responsibilities in ANTARES. Scientific harvesting started in 2008, with e.g. best limits on neutrinos from point sources. An interesting initiative has been taken by the AHE group for joint multi-messenger research between the ANTARES and VIRGO/LIGO collaborations. Finally, the group is actively involved in R&D for the European KM3NET, exploiting its expertise in photo-detection.

In the field of ultra-high-energy cosmic rays (UHECRs) the AHE group realised major contributions to the hardware and science of the Pierre Auger Observatory, gaining global recognition for data analysis and interpretation in this field. The modelling and interpretation addressed e.g. the acceleration and propagation of Galactic cosmic rays as well as UHECRs. A major result is the shown degeneracy of the measured UHECR energy spectrum, whether one is dealing with just protons or mixed nuclei, leading to different conclusions on the observed 'ankle' in the spectrum and the phenomenology of the transition from a galactic to an extragalactic origin. The suggestion from Auger measurements of a transition towards heavier nuclei at the highest energies is now shared by a large part of the international community.

The group is now focussing on the development of the international JEM-EUSO mission, to be flown aboard ISS, with a preliminary balloon campaign EUSO Balloon approved by CNES with flights in 2014.

Assessment of the unit's academic reputation and appeal

The AHE group has significant responsibility in many national and international projects, studies, and proposals, such as: Co-PI INTEGRAL/IBIS; Leading M3 mission proposals to ESA (CAPSiTT, COSPIX); Simbol-X studies (PI, Project Scientist): TARANIS Co-PI XGRE, project manager; contribution to ASTRO-H, Co-PI; scientific contributions to HESS, HESS2, CTA, ANTARES working groups, AUGER; EUSO-balloon, project manager; JEM-EUSO National PI.

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

In its R&D and instrumental activities the group has direct links with industry. An example is an international collaboration with industrial partners, in particular THALES, for the development of the new generation of semiconducting sensors. The AHE group is also coordinating the European Network ITN 'INFIERI' (Intelligent FAST Interconnected and Efficient devices for Frontier Exploitation in Research and Industry) for the development of hightech solutions for signal processing on detectors (front-end) or final processing (far-end), including again THALES. Involvement in the production of 3D Compton imaging software offers the possibility for multiple applications in society.

The AHE group has been very active in organizing outreach activities such as many outreach conferences, bars des sciences, many outreach articles and seven books, exhibitions, creation of the "House of Astroparticles" in the 3D virtual environment "Second Life". Furthermore, a series of conferences and lecturers at the "Open University" (DAPAEUS) were given.

Assessment of the unit's organisation and life

The group is involved in a diversity of activities, projects and techniques organized in sub-groups operating in a large number of separate national and international collaborations. The interactions in the sub-groups are intense, and the organisation within space projects is of an international standard. There is significant overlap in the scientific themes addressed by the different projects. However, due to the various commitments of the sub-groups in the many international (closed) collaborations, the AHE group meetings, seminars, and further interactions between the subgroups are irregular. The interdisciplinary nature of AHE can be better exploited, also in the education of students.

Assessment of the unit's involvement in training through research

The AHE staff has been strongly involved in research education activities, through the supervision of many Licence, Master (25) and PhD students (17, of which 7 defended their theses), the participation in various academic programs and networks, the development of innovative education tools and programs, the writing of books and lecture notes, e.g.:

-

Founding

Assessment of the five-year plan and strategy

The combination of studying energetic particles (electrons, protons, nuclei), non-thermal astronomy (X-rays, gamma rays, TeV photons) and neutrino astronomy in AHE, collaborating in APC with teams of the ADAMIS, Theory and Neutrinos groups, makes APC a strong site for Astroparticle Physics. The AHE group has been involved in major international projects in this field, and, building on the acquired expertise, has a very ambitious five-year plan. The aim is to maintain a balance between an effective participation in the next-generation experiments, data analyses and astrophysical interpretation. Seeking to play a leading role in the definition and preparation of future experiments, the group has recently strengthened its instrumental component in the field of photo-detection and innovative signal processing solutions. In Europe, it is leading the development of a next-generation Compton telescope for a major step in studies in the low-energy gamma-ray domain. However, there are significant uncertainties. Several of these plans involve large international programmes (JEM-EUSO, CTA, KM3NET, international X-ray observatory, SVOM, Compton Space telescope) for which funding, international selection and/or time lines are uncertain. All of these projects will come to fruition at the end of this decade or even later. But, there is a sufficiently high probability that a number of these international projects will be selected, and the AHE group is in an excellent position to provide significant or leading contributions.

Team 3 :

Cosmology and Gravitation

Name of team leader: The Cosmology and Gravitation group has strong and active teams working in three main areas of research: (1) Experimental investigations of the cosmic microwave background, with particular emphasis on the detection of Bmodes that could provide the signature of inflation; (2) Cosmological analysis of large spectroscopic and imaging surveys for the determination of constraints on the nature of dark energy; and (3) The detection of gravitational waves using both ground-and space-based detectors.

In the first area, the group has played a leading role on the Planck HFI experiment, having taken charge of the polarization characterization of that instrument, the removal of cosmic ray impacts, the correction for non-linearities in the instrumental response, the estimation of noise parameters, and the characterization of the beams at different scales. They have also worked with the ADAMIS group on the identification and removal of foregrounds. On the analysis side, they have participated in investigations of polarization in general, the search for non-Gaussianities, and the study of Galaxy clusters through the Sunyaev-Zeldovitch effect. This group also includes an active hardware development component through the "Laboratoire millimetrique", which has pioneered the development of transition edge sensors and kinetic induction detectors.

The group working on the cosmological analysis of large galaxy surveys is heavily in BOSS, EUCLID, and LSST. On BOSS, they played a key role in the first detection of the baryon acoustic oscillations signal in the Lyman-alpha forest toward distant quasars. On EUCLID, they are leading the planning for the merging of ground-based visible-band data with the EUCLID infrared data for the determination of photometric redshifts. On LSST, they are leading the software development for the camera control systems, and are key members of the photometric calibration working group.

The gravitational wave group is one of the major players of the eLISA project, and its precursor LISAPathFinder mission. APC contributed significantly to the writing of the "Yellow Book" that was submitted to ESA in support of this project, and played a key role in the simulation of detector performance and parameter estimation. For LISAPathFinder, the FACe was chosen to host the "Complementary Data Centre", which will support ESA's main data center. On Virgo, this group has been involved in all aspects of the data taking and data analysis of the existing experiment, and the design and construction of the Advanced Virgo upgrade. In particular for Advanced Virgo, they have led the optical design, and taken responsibility for the construction of the mode-matching telescopes. Through their "Laboratoire optique", they have also been researching new techniques to reduce thermal noise in the mirrors of future gravitational wave detectors.

Assessment of the unit's academic reputation and appeal

This group is very well known in Europe through the key roles they have played in the Planck mission and in the European gravitational wave community. In particular, a member of this group is one of three "main investigators" for the eLISA consortium, and other members have won significant awards of distinction both inside and outside France. The group has attracted excellent postdocs and students for all of its activities.

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

Through its two laboratories and through its hardware development programs, the Cosmology and Gravitation group has strong connections to industry. In addition, members of this group have been very active in education and public outreach programs through exhibitions, activities with high schools, public conferences and continuing education. In particular, through the "Université Ouverte", members of this team have taught cosmology-related courses to the public over a wide range in age and background.

Assessment of the unit's organisation and life

The group appears to be functioning well, and morale is very high. Coherence among the diverse programs is achieved via bimonthly meetings and through a journal club. The present leadership is strongly supported by the staff. The neutrino group at APC and its experimental projects are internationally highly visible. The group consists currently of 13 staff scientists, 5 Postdocs, 5 PhD Students and visitors, and pursues a well tailored science program with a focus on the reactor neutrino experiment Double Chooz, the solar neutrino experiment Borexino, and on future projects addressing the measurement of the neutrino mass hierarchy with atmospheric neutrino with the deep-sea water Cherenkov telescope Orca and with long-baseline neutrino oscillation project Laguna-LBNO. The latter also aims to address CP violation studies in the Lepton sector.

The Double Chooz experiment provided the first measurement of the neutrino mixing angle θ13 using antineutrinos from the nuclear power reactor with a novel type of detector. The experimental result of Double Chooz is a ground breaking discovery in the field, which is recognized worldwide and which is of a transformational nature with wide ranging implications. International competitors are the Chinese-US Daya Bay and the South-Korean Reno experiments. The APC team, together with the group from CEA Saclay, are the initiators and the core teams of the experiment. APC scientists have leading roles in the Double Chooz experiment, including the spokesperson and physics analysis coordinator, and have important instrumental responsibilities. The first presentations to the science community at international conferences were made by APC members.

Despite limited funding, the APC neutrino group also made important contributions to the solar neutrino experiment Borexino. This includes the precision measurements of solar 7Be neutrinos, low-threshold 8B neutrino spectral analysis, first measurements of solar pep-neutrinos and the energy dependent mapping of the matter induced neutrino conversion transition in the sun (MSW effect). Further initiatives which generated worldwide visibility and interest, are the reactor anomaly which could be reconciled with eV sterile neutrinos. One APC scientist obtained an ERC grant to realize an artificial neutrino source to be deployed in a large liquid scintillator detector at KamLAND, and a Borexino to search for very short baseline oscillations, which would be driven by sterile neutrinos at the eV scale.

Assessment of the unit's academic reputation and appeal

Based on its reputation, the neutrino group succeeded to attract first class scientists from abroad which is reflected in the hiring of staff from the UK, Germany and Italy, as well as excellent PhD students and postdocs. The reputation of the group is also manifested by a CNRS Médaille, an European ERC grant, an ANR grant, as well as the European funded Laguna-LBNO design study within FP7. Members of the neutrino group have been organizers of several international conferences, hosting the European doctorate school ISAPP, and are members of international scientific committees (e.g. CERN SPSC). As a core team of the Double Chooz experiment, the neutrino group serves also as a hub for the international collaborators from Europe, Russia, USA, Brazil and Japan. The academic reputation resulted also in the recent hiring of two staff and the attraction of a neutrino theorist to the theory group.

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

The neutrino group obtained strong regional support from the Champagne Ardenne region for the Double Chooz experiment. In return, the group organized a conference in the region and regular public lectures within the Double Chooz outreach program. One group member is a delegate in the Vienna IAEA as neutrino expert, in the IAEA project 'neutrinos for safeguard and non-proliferation'. The neutrino group gave public outreach talks in the Palais de la Decouverte, a member of the group wrote a book on neutrinos for the general public and the Double Chooz experiment inspired a cartoon widely read in France. The digital signal converter (FADC) used in the Double Chooz experiment has been developed together with an Italian company and the device is now commercially available to other experiments and to industry.

Assessment of the unit's organisation and life

The members of the neutrino group show an extremely enthusiastic spirit and have close links between projects. Moreover, there is strong transverse communications with other units. For example, the neutrino group leader was previously a member of the high-energy group working on Antares. A member of the neutrino group is the current deputy APC director.

Assessment of the unit's involvement in training through research

Members of the neutrino group are co-founders of the international doctorate school IDAPP and had several international co-supervisions of PhD students. In total 8 PhD students joined during the recent period and they are fully integrated in the scientific activities of the group. All PhD students who finished during the period under review found postdoc positions. From the recent four postdocs (three of them on-going), one won the CNRS competition and obtained a permanent position at APC. The group has also been very active in training master students, in total amounting to 13.

Assessment of the five-year plan and strategy

The present focus of the neutrino group is the completion of the Double Chooz experiment, and on a precision measurement using both rate and shape of the energy spectrum to reduce the uncertainties of the mixing angle θ13. With less resources, but not with less relevance, the group continues to contribute to Borexino with near term goals to measure or limit the solar CNO flux, as well as a measurement of neutrinos from the Earth with increased statistics. At intermediate time scales, the neutrino group pursues the Ce-LAND (ERC grant) and SOX neutrino source projects for sterile neutrino search. It should be mentioned that the neutrino group at APC is the only group which has the potential to pursue both projects synergistically, opening a unique possibility at APC, exploring the possibility to deploy a Ce neutrino source both in Borexino and KamLAND.

Given the large value of the mixing angle θ13, a feasibility study for determining neutrino mass hierarchy using atmospheric neutrinos in a deep-see Cherenkov detector (ORCA) has commenced recently at APC. The APC neutrino group was successful in obtaining an ASPERA grant in cooperation with the south-pole-based IceCUBE/Pingu project. Further strategic developments concern possible participation in the liquid argon direct Dark Matter search experiment Dark Side which is considered synergistic with the low-background expertise of the group and the Laguna-LBNO design study, also employing liquid argon as detector medium. The latter is an international long-term project, which likely will only be realized in a US/European collaboration.

The strategy of the neutrino group guarantees that transformational physics results can be expected in the future, comparable to their current achievements. Assessment of the unit's organisation and life

The group appears to function smoothly and without any visible problem. It organizes regular seminars as well as topical workshops that are well attended by members of the group as well as by theorists from the greater Paris area. Integration of the group in the FRIF (Federation de Recherche pour les Interactions Fondamentales), which regroups several theory groups in Paris (ENS, Paris 6, Collège de France, IAP), has been launched some 8 years ago, so far with partial success, but a higher involvement is being planned.

Assessment of the unit's involvement in training through research

The theory group is strongly involved in teaching (even by some of the CNRS staff) at all levels (undergraduate, master and Ph. D.). Some teaching is also given outside of Paris 7 (e.g. at the Ecole Polytechnique).

Assessment of the five-year plan and strategy

The future plans of the group are sound: they will continue the traditionally strong lines of theoretical research with very good interactions with the various experimental groups at APC and an increased interaction with other theory groups in Paris (via their membership in the FRIF). Hopefully their search for a GW theorist will also succeed.



  Grading table of the team: location of the unitThe Laboratoire Astro-Particule et Cosmologie (APC) was formally created in 2005 to provide a coherent focus for the emerging fields of particle astrophysics and cosmology within the Paris area. The scientific teams that comprised the laboratory began their association in the period 1999-2004 in three main areas: (i) High Energy Astrophysics, (ii) Cosmology and Gravitation, and (iii) Neutrinos. They moved to the new campus of Paris Rive Gauche (PRG) in 2006 along with the transfer of the University Paris 7 Diderot to that location. The laboratory is supported by a mixture of agencies and funding sources, including CNRS (both IN2P3 and INSU), CEA, Observatoire de Paris, and the Paris Diderot University. The University has devoted a strong hiring program to APC, averaging roughly 2 to 3 positions per year in the period 2001-2010.

N4:

  Other permanent staff (without research duties) 1 1 Other professors (PREM, ECC, etc.) N5: Other EPST or EPIC researchers (DREM, Postdoctoral students, visitors

  leader: Mr Antoine KOUCHNER sinceOct. 2012 (Ms Alessandra TONAZZO before) Other permanent staff (without research duties) (persons/FTE) N4: Other professors (PREM, ECC, etc.) (persons/FTE) 1 1 N5: Other EPST or EPIC researchers (DREM, Postdoctoral students, visitors, etc.) (persons/spent at least 12 months in the unit Number of Research Supervisor Qualifications (HDR) taken 2 Qualified research supervisors (with an HDR) or similar positions 5  Detailed assessments Assessment of scientific quality and outputs

  Other permanent staff (without research duties) N4: Other professors (PREM, ECC, etc.) 1 1 N5: Other EPST or EPIC researchers (DREM, Postdoctoral students, visitorsspent at least 12 months in the unit 7 Number of Research Supervisor Qualifications (HDR) taken 2 Qualified research supervisors (with an HDR) or similar positions 12

-

  APC scientists developed key new techniques for the estimation and removal of foregrounds in the Planck CMB dataset, which have attracted international attention at the highest level,-They have also made a very strong contribution to Planck science output, with particular attention to systematics, -APC has spearheaded the effort to maintain momentum behind LISAPathfinder and eLISA. FACe is playing a substantial role in helping to facilitate French and European activity in this area,

-

APC scientists continue to lead the analysis of data from IBIS/ISGRI instruments on INTEGRAL,

-

The laboratory hosts a vigorous theoretical effort, with good connection to its experimental program, -APC has established strong participation in HESS, facilitating multi-wavelength studies of nonthermal astrophysical sources, and leading to a future significant role in CTA,

-

The laboratory has played major hardware and interpretive roles in the Pierre Auger Observatory,

-

The laboratory has made important contributions to the ANTARES project, -APC scientists have established a strong publication record for the Laboratory as a whole.

  Mr Etienne PARIZOT

	Workforce
	Team workforce	Number as at 30/06/2012	Number as at 01/01/2014	2014-2018 Number of project
					producers
	N1: Permanent professors and similar positions	6	6		6
	N2: Permanent EPST or EPIC researchers and similar positions	13	14		14
	N3: Other permanent staff (without research duties)
	N4: Other professors (PREM, ECC, etc.)
	N5: Other EPST or EPIC researchers (DREM, Postdoctoral students, visitors, etc.)	12	6		6
	N6: Other contractual staff (without research duties)
	TOTAL N1 to N6	31	26		26
	Team workforce	Number as at 30/06/2012	Number as at 01/01/2014
	Doctoral students	7
	Theses defended	6
	Postdoctoral students having spent at least 12 months in the unit	9
	Number of Research Supervisor Qualifications (HDR) taken	3

  Mr Yannick GIRAUD-HÉRAUD

	Workforce
	Team workforce	Number as at 30/06/2012	Number as at 01/01/2014	2014-2018 Number of project
					producers
	N1: Permanent professors and similar positions	8	7		7
	N2: Permanent EPST or EPIC researchers and similar positions	10	11		11
	N3: Other permanent staff (without research duties)	3	2
	N4: Other professors (PREM, ECC, etc.)
	N5: Other EPST or EPIC researchers (DREM, Postdoctoral students, visitors, etc.)	3	3		3
	N6: Other contractual staff (without research duties)	1	1
	TOTAL N1 to N6	25	24		21
	Team workforce	Number as at 30/06/2012	Number as at 01/01/2014
	Doctoral students	8
	Theses defended	12
	Postdoctoral students having spent at least 12 months in the unit	4
	Number of Research Supervisor Qualifications (HDR) taken	4
	Qualified research supervisors (with an HDR) or similar positions	12

 Detailed assessments

Assessment of scientific quality and outputs

 Supervising bodies' general comments

Assessment of the unit's involvement in training through research

The Cosmology and Gravitation group has been active in the training of students. There have been 12 doctoral theses completed during the past 5 years, and 8 are on-going. In addition, members of this group have supervised 15 M1 students and 14 M2 students. These are impressive numbers for a group of this size. In addition, group members have been active in Summer Schools in their respective fields.

Assessment of the five-year plan and strategy

The long-term strategy involves a continuation of vigorous activity in all three areas, with a gradual transition of some members of the group from CMB research over to the analysis of large galaxy surveys, as EUCLID and LSST come on line. While this plan is well-motivated, it will take care and monitoring to ensure that that transition is effective, given the differences in culture between these two fields. The future of the space-based gravitational wave effort remains uncertain, and will depend critically on the success of LISAPathFinder. However, APC is well-positioned to capitalize on that success as this program moves forward.

 Detailed assessments

Assessment of scientific quality and outputs

The Theory group of APC covers, from a theoretical viewpoint, the research topics of the lab as well as some more formal lines of research. It consists of about 15 permanent members, evenly shared between University and CNRS, and about the same number of non-permanent members in the form of post-docs and Ph. D. students. It also benefits from the presence of three associate members (spending regularly a share of their time at APC) and of the proximity of the new PCCP Center directed by Nobel Laureate Mr George SMOOT.

The following topics have considerable overlap with the experimental activities of the lab:

-Theoretical cosmology and models of inflation to be tested through their observable predictions about non-gaussianities and polarization in the CMB anisotropies, -Models of modified gravity, particularly those inspired by the possible existence, suggested by string theory, of extra dimensions of space. This is an area in which the group have given pioneering contributions,

-

The theory of neutrino masses and oscillations of direct evidence to the Double Chooz experiment has been adequately reinforced with a new recent recruitment,

-

The theory of cosmic ray acceleration with interesting implications for the experimental program on UHECR of the lab (AUGER),

In all these areas the APC group is at the highest level of international standards.

One regret is the lack of a theoretical component to support the experimental activity of APC in gravitational wave research (Advanced VIRGO, LISA pathfinder) after the departure of a leading theorist in 2005.

More formal lines of research include some of today's "hot topics":

-Holography with application to Heavy Ion collisions and Condensed Matter Physics, -Higher-spin theories in curved backgrounds (like Anti de Sitter spacetime), -Quantum Field Theory in curved space-time (with some possible application to cosmology), -Coherent state quantization.

Assessment of the unit's academic reputation and appeal

On the whole: a very good level of research with a good and balanced spectrum of topics for an experimentdriven lab.

The group is clearly very attractive to postdocs to Ph. D. students (a large share of APC postdocs and Ph. Ds for the group's size), and to visitors, and has excellent connections with other groups worldwide (DAMTP, Cambridge UK and Yukawa Institute, Kyoto, for instance). It has been co-organizing international conferences with the Perimeter Institute (Canada) and the Solvay Institute (Brussels). It was also able to attract both European and French funding through 1 ERC and 3 ANR grants, respectively.

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

The group has also high visibility and cultural impact with respect to the public through the organization of public conferences and exhibitions, popular science books and journals.


President Michel Cosnard

Graham Burton

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

MANAGEMENT TEAM

The proposed director and deputy director are respectively Mr Thierry Fournier (DR Inserm) and Mr Fédéric Barbut (PUPH, Biologiste).

HCERES NOMENCLATURE

SVE5 SCIENTIFIC DOMAIN

The focus of the future 3-PHM unit's research is an evaluation of how two biological systems, the placenta and its placenta, and the neonate's intestinal microbiota, influence short term and life-long health of the mother and its child.

The placental research programme comprises basic science and translational axes. The former involve i) the regulation of placental development by environmental cues and the molecular signalling networks involved, and ii) the role of the placenta as a protective barrier through selective transfer and metabolism of drugs and toxins. The latter involve: i) an investigation of blood flow through the placenta using new imaging techniques and computational modelling, and ii) the identification of maternal biomarkers of placental dysfunction and their correlation with cell biological models of abnormal trophoblast differentiation.

The microbiota programme focuses on how the intestinal microbiome is established in the neonate, how it is related to maturation of the newborn's immune system and associated to enteropathies and future health of the child, and how it may be manipulated therapeutically.

A new integrated project arising from the merger is to explore the maternal and placental microbiota, and its relationship to that of the neonate.

UNIT WORKFORCE

GLOBAL ASSESSMENT OF THE UNIT

The proposed merger brings together complementary expertise that opens new opportunities to explore topical issues such as the characterisation and metabolic activity of the placental microbiota, and its involvement in health and disease.

The combined research output of the units U1139 and EA4065 is very good, and there are strong translational links to clinical obstetrics and perinatology, including the role of the placenta in protecting the fetus against environmental toxins, the development of diagnostic test and therapeutics for pre-eclampsia, and the involvement of the microbiome in neonatal health and disease.

Both U1139 and EA4065 have an excellent record in the training of young researchers, and very good public engagement with their research activities.

With the restructuring merger, it is anticipated that unique cross-disciplinary research will lead to highprofile research outputs that will enhance the international profile of the 3-PHM Unit.

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 International evaluation and accreditation

INTRODUCTION

  HISTORY AND GEOGRAPHICAL LOCATION OF THE UNITThe proposed new unit named UMR-S 1139 "Pathophysiology & Pharmacotoxicology of the Human Placenta; pre & postnatal Microbiota" (3 PHM) will result from the merger of two units: the UMR-S1139 "Pathophysiology & Pharmacotoxicology of the Human Placenta", created in January 2014 under the direction of Mr Thierry Fournier, and the EA 4065 "Intestinal ecosystem, probiotics, antibiotics" created in 2006, renewed in 2010, and again in 2014 and currently headed by Ms Marie-José Butel. The new unit will be located at the Faculty of Pharmacy of Paris, 4, avenue de l'Observatoire, 75006 PARIS (the same location as the current units).

HCERES scientific officer: Mr Jean Edouard GAIRIN Representatives of supervising institutions and bodies:

	Unit name:	Pathophysiology & Pharmacotoxicology of the Human Placenta, pre & postnatal Microbiota
	Unit acronym:	3 PHM
	Requested label:	Inserm and Université Paris Descartes
	Application type:	Restructuring
	Current number:	UMR-S 1139
	Head of the unit (2017-2018):	Mr Thierry FOURNIER
	Project leader (2019-2023):	Mr Thierry FOURNIER
	Number of teams or themes: 1
	COMMITTEE MEMBERS
	Chair:	Mr Graham BURTON, University of Cambridge, UK
	Experts:	Mr Loic BLANCHON, Université de Clermont Auvergne
		Ms Joelle DUPONT, Inra de Tours (representative of INSERM CSS)
		Mr Loic FAVENNEC, Université de Rouen
		Mr Laurent GALIO, INRA, Jouy-en-Josas (supporting personnel)
		Ms Vassilia THEODOROU, Université de Toulouse
		Mr Stefano MARULLO, Université Paris Descartes
		Ms Sylvie ROBINE, Inserm
		Mr Michel VIDAL, Faculté de Pharmacie


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.

 Introduction

After its first creation as an INSERM unit in 1995 under the direction of Ms Danièle EVAIN-BRION, the current INSERM Unit was recreated in 2006 (U767 / Normal and Pathological Pregnancy) with the same director. The main research focus of the UMR INSERM S767 is to study the development and functions of the human placenta during normal and pathological (preeclampsia, intra-uterine growth retardation, prematurity) pregnancies. In particular, the team studies the molecular and cellular mechanisms involved in the invasion and differentiation of (villous and extravillous) trophoblastic cells. The UMR INSERM S767 is located at the « Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes". 300 m2 of research surfaces are devoted to this unit, which has also access to platforms from the IFR and the University. The internationally recognized expertise in human placental development, physiology and functions (focused on trophoblastic cells) during normal but also pathological pregnancies.

The development of acknowledged cellular models representative of trophoblastic environment and the development of a new model : the perfused cotyledon for the pharmacotoxicology project.

The clinical relevance of the research questions with translational applications to major human pathophysiological pregnancies affecting around 70 000 cases per year (9% of the French annual pregnancies).

The very good exploitation of the scientific work in terms of echographic and biomarkers development.

The strong ability to obtain some important fundings during the last 4 years : 3 ANR projects and private grants.

A central and leader position with the scientific and clinician community working on obstetrics in Paris, with the establishment of a real and functional network based on numerous institutions as RTRS "Pregnancy and Prematurity" and the PremUp Foundation, Labex or Equipex for example.

An important number of publications (145 ACL publications) in the best journals of the specialties "Biology of Reproduction, Obstetrics and Gynecology or Endocrinology".

The support of the faculty and university and the opportunity of a future evolution of the faculty toward a research centre.

Weaknesses and threats:

The major weakness is linked to the lack of high rank publications in general journals potentially explained by the highly focused research topic.

The absence of european or international funding networks. The future move to the new research building occuring during the future 4 years period potentially affecting the team's life and production.

Recommendations:

The new scientific fields proposed in the project (pharmacotoxicologic and the oxidative status of the human trophoblastic environment) have to be supported to strengthen up and consolidate the global approach of the unit in terms of placental pathophysiology.

The Unit has to reinforce its network in terms of clinical and scientific collaborations, collections of biological samples related to pregnancies, and socio-economic relations in order to stay among the most acknowledged research laboratories in terms of national and international lisbility.

Due to its expertise, the results obtained and the high level of the projects, the team has to produce some publications that can be submitted to generalist journals with a high international rank, and not to keep publishing in the ones they have been used to, as they belong to the restricted scientific field "Biology of Reproduction, Obstetrics and Gynecology or Endocrinology".

 Detailed assessments Assessment of scientific quality and outputs:

There are regular publications (145 papers type ACL in the 4 last years) in the best journals of the field "Biology of Reproduction, Obstetrics and Gynecology or Endocrinology", with the 5 most important publications since 2007 listed by the team published in Endocrinology (2), J. Clin Endocrinol. Metab., Am. J Physiol. Cell. Physiol and FASEB.

The (clinical and fundamental) research questions are very original with an important obstetrical relevance and based on an international expertise on placenta. The results are established with specific models (primary cultures, established cell lines, perfused cotyledon) well controlled and validated.

The translational research topics at the clinical research interface led to echographic developments and in vitro diagnosis assays.

There have been no publications in general journals or in journals with high impact factors.

Assessment of the unit's academic reputation and appeal:

There is an important international academic attractiveness of the team members with 25 guest international conferences participation. The team members belong to the different international committees working on placental science (IFPA, Trophoblast Research Center of Cambridge…) and are members of the editorial board of the journal Placenta.

National and international collaborations are well established to support the different past, present and future projects.

The acknowledgment of the team is attested by obtaining important institutionnal financial support (3 ANR) and private grants.

The team created and organised the first international symposium of the "Francophone Placenta Group" in Geneva (2012) and was designated for the organisation of the Congress of International Federation of Placenta Associations in Paris (2014).

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

This point is excellent in terms of network participation. The Inserm U767 team founded the RTRS "Pregnancy and Prematurity" research and care network. The PremUp foundation was also created by the U767 with other parterns. PremUp organised annual meetings on perinatality with public participation and published numerous press articles, films and interviews.

Assessment of the unit's organisation and life:

The entity governance is recognised as performant by staff members. This point has been clearly mentioned by both engineers and technician staff, during their interviews.

A regular (monday) meeting was organized for all the team to talk about scientific, administrative and technical aspects.

The need for a future potential help (by a recruitment) was underlined by engineers and technician staff concerning the administrative charge of the future director in order to be able to conduct "as well as before" his scientific team. The team didn't mention any responsiblity in national and international training networks.

Assessment of the unit's involvement in training through research:

Assessment of the five-year plan and strategy:

The goal of the research project 2014-2018 is globally to obtain better knowledge of human placental development and function in normal and pathological conditions in order to improve early screening and care of the main obstetrical diseases associated with placental dysfunctions with a specific focus on the floating chorionic villous. The study will analyse the impact of the environment within the intervillous space in both physiological and pathological conditions on the formation, integrity, exchange andhormonol fucntions of the chorionic villous, the functional unit of the human placenta.

The project is clearly divived in work packages: WP 1: Formation of the placental barrier "Formation of the placental barrier" represents a very interesting working package of the future unit, which has a longstanding and worldwide-recognized expertise in studying mechanisms controlling trophoblast cell fusion which represents the key event in placental barrier formation. Understanding regulation of trophoblast cell fusion is not only fundamental to our understanding of placental function and hence fetal nutrition and wellbeing during normal pregnancy, but also critical to unravel mechanisms involved in the pathogenesis of diseases arising during pregnancy such as preeclampsia, intrauterine growth restriction or trisomy 21. This is of particular relevance to the human health in later life, since it became evident that abnormal fetal growth during pregnancy predisposes to a variety of adult diseases such as hypertension, cardiovascular problems or metabolic disorders.

As mentioned above, researchers of the unit are regarded as leading experts in the field since they unraveled numerous key mechanisms in trophoblast fusion such as the role of cAMP signaling and placental hormones. Importantly, they could also demonstrate that the fusion process and production of different forms of the pregnancy hormone called human chorionic gonadotrophin were impaired in trophoblasts of pregnancies carrying fetuses with trisomy 21. Hence, research of the unit not only investigates basic mechanisms in trophoblast differentiation but also has a strong focus on failures in this process in pathological pregnancies which will likely lead to the identification of novel biomarkers and improvement of diagnostic tools long-term.

The head of this working package has convincingly demonstrated that his expertise, knowledge and current research ideas will lead to further important insights in this particular area of pregnancy research. Besides his excellent publications in the field he gave an outstanding presentation on the current data, ideas, and projects during the AERES evaluation. As part of his PhD thesis he discovered that abnormal hCG (human Chorionic Gonadotropin) signaling impairs trophoblast fusion as occurs in trophoblasts derived from trisomy 21 placentae. He also identified other important regulators of trophoblast cell fusion such as ZO-1 and contributed to our understanding of the mesenchymal-trophoblast cross talk in the placental villus. His recent activities to identify the role of phosphatases and cAMP-dependent macro-complexes controlling trophoblast cell fusion sound very interesting and promising for the future since much remains to be learned about physiological and abnormal trophoblast differentiation.

It is also worthwhile mentioning that during his postdoctoral studies in Oslo, Norway, he produced excellent publications on AKAPs, (A-kinase anchoring proteins) protein-macro complexes controlling and organizing cAMP signaling in a spatial and temporal manner.

The project also presents interesting novel techniques to studying the protein interactions in macro-complexes of the placenta and to analyze trophoblast cell fusion, which are already established in the laboratory. Moreover, the role of different types of phosphodiesterases (PDE), inactivating cAMP, in trophoblast fusion and their potential roles in pregnancy disorders are largely unknown. Unpublished data of the group nicely demonstrated that different enzymes of the PDE family are involved in this fusion process.

In conclusion, the strong expertise in cell-and molecular biology of the placenta supported by excellent collaborations will allow the PI to study AKAPS and other interesting protein assemblies in the setting of physiological and pathological trophoblast function and differentiation which represents a novel and promising research direction of the working package within the next years.

WP2 : Ontogenesis of the placental barrier

This working package will be focused on the ontogenesis of the placental barrier with two parts: (i) the role of the oxygen environment in the trophoblastic differentiation and functions; and (ii) the role of nuclear receptor PPAR gamma (PPAR and its target genes in placental development. Up to date, the redox status of trophoblastic cells is poorly known. For this first axis, the hypothesis is that oxidative/nitrosactive stress inside the trophoblasts due to changes in oxygenation (occurring well established steps of the placental development) may have physiopathological consequences (preeclampsia and IUGR) for trophoblastic differentiation and functions; and for the passage and metabolism of xenobiotics during pregnancy. The second part is based on previous interesting papers of the team identifying the important roles of PPAR in trophoblastic functions. The present project will develop the involvements of PPAR target genes during human trophoblastic differentiation. They also hypothesized that a dysregulation of PPAR , HCG and LOX could occur in placental pathologies.

* Strong points:

-The team leader's research has contributed in a fundamental manner to important advances in placental endocrinology. His studies have established the key roles of peptide hormones, such as HCG in the control of trophoblast differentiation and have contributed to the elucidation of current concepts on the role of the transcription factor, PPAR in placentation. Recently his team has shown that a hyperglygosylated form of HCG (H-hCG) exists in the placenta with a direct role in the control of trophoblast invasion. As a result of this insightful work concerning HCG and PPAR , this team became an independent part of the teams working in the field of hCG and PPAR in the placenta.

-The new project proposes a large and novel number of hypotheses focusing on the understanding of normal and pathological pregnancies, with an important feasibility in terms of technical and scientific support.

-The team has a strong support from the actual authorities: University, Hospital and Faculty of Pharmacy.

-This redox status project will be supported by the presence of newly recruited teaching-researchers specialized in this field.

* Weak points:

-The committee believes that with the workload that the team (and also unit) leader will have, he won't be able to run day-to-day specific projects and he needs to delegate some of his own proposed projects to young researchers.

-With the proposed new project the unit should consider the development of animal models, a criterion that was missing during the last term.

WP3: Placental transfer and metabolism of xenobiotics

This is one of the main new research topics of Unit UMR-S767. Placental transfer and metabolism of drugs and environmental toxins (such as benzo[a]pyrene) are studied using ex vivo human perfused placental cotyledon model. In the project, two types of immunosuppressive drugs (tacrolimus and cyclosporine) will be studied. First results have been obtained on tacrolimus which transfer has been evaluated using control placentas and placentas of transplanted women. This approach is completed by in vitro studies using trophoblastic primary cultures eliciting the evaluation of the xenobiotics impact on cell differentiation. Cellular and lipid markers will be characterized by means of a mass spectrometry, especially after long term exposure in placentas from transplant recipients. This topic is strongly supported by the Faculty of Pharmacy as demonstrated by the recruitment of a Professor in Biochemistry, previously working on the model of perfused placental cotyledon. Several fundings support this activity: ANR "Placentox", LFB or Mutuelle generale.

The perfused cotyledon model is simple, elegant and not very expensive. However, it only offers a localised, restricted and fixed view of pregnancy. Nevertheless, it can give first data on drug availability over the placental "filter". One interesting point is that the studies are not only performed on normal placentas but also on placentas from transplant recipients eliciting the study of the impact of the disease and/or the chronic drug use on placental transfer.

WP4: Translational Research

The first translational theme deals with the study of the maternal blood flow within the intervillous space by two approaches. Indeed, the researchers plane to assess the impacts of perturbations of maternal hemodynamics on the biological properties of the villous trophoblasts by (i) identifying the impact of the shear stress on the biological functions of human syncytiotrophoblasts and by (ii) examining the placental vascularization in normal and pathological pregnancies using ultrafast imaging (micro-Doppler). The second translational theme concerns the identification of biomarkers of abnormal trophoblastic differentiation in placentas with aneuploidy (trisomy 18, 13, 21, Turner syndrome 45X0). This work will be realized using a mixed approach: identification of biomarkers at cellular levels in cultures and after a validation of the candidates at the clinical interface. The feasibility of both projects is excellent due to the biological and obstetrical positions of both teaching-researchers at the hospital. This was also completed by an important competence of both project leaders in terms of scientific and technical fields. The recruitment of patients will be clearly helped by the different collections strategies and tools previously installed.

In addition, since 2006, the director of the unit UMR-S767 INSERM has created and directs the foundation for scientific cooperation on perinatality, PremUP (www.premup.org). PremUP meets two main concerns including a better understanding of fetal growth disorders and provide assistance to patients. PremUP includes 6 maternity and neonatology units type 3 (with 20 000 births and 2500 premature babies) and research centers (10 INSERM units, 1 CNRS unit, 1 INRA unit, 1 IRD unit, 2 Centers for Clinical Investigation and 1 Center for Epidemiological Investigation). In addition, PremUP supports Perinat Collection that was selected in the first call for the projects EQUIPEX. This project allows collecting, preserving and developing large collections of fetal and perinatal samples. These collections are also documented and associated to clinical data and imaging in reproducible conditions. The PremUP foundation and Perinat collection are both unique tools to follow pathological pregnancies, the birth and the childhood and contributes in a unique way to improve the management of perinatal problems, especially those of prematurity. Finally, Prem Up and Perinat Collection are keys actors in structuring the French research from the physiology of human placenta to prematurity.

Conclusion:

The proposed project has a very important obstetrical relevance, mixing fundamental, clinical and translationnal approaches.

The work already done is of excellent quality, allowing this team to obtain national and international acknowledgment.

The feasibilty of the proposed projects is good due to the previous establisment of scientific, socio-economic and clinical networks. First of all, we would like to thank the committee for their report concerning the evaluation of our research unit and the helpful and positive comments of the referees. We have no general comments on the report, which covers and describes well the activities of our research unit. We wish nonetheless to bring some insights about the few specific points raised in the three recommendations of the report, and concerning animal models, as developed below.

1/ Research on the pharmacotoxicology of the human placenta currently benefits from financial support (Placentox) from ANR and another proposal is under evaluation. This latter financial support will allow the recruitment of a doctoral and/or a post-doctoral fellow to reinforce research on this topic. Research on the ontogenesis of the placental barrier and oxidative status of the trophoblast will be reinforced by the recruitment of an AHU in 2014. One funding proposal is under evaluation and will allow recruitment of a post-doctoral fellow to support this theme. In addition a fellowship for a Canadian post doc is under evaluation. We have also posted an offer for a CR position by internal mobility.

These two topics will benefit from the technical expertise of an AI from January 2014 and of a MCU position (September 2014) thanks to the arrival of a PU and a PUPH in the team.

2/ As mentioned in the report, our research is part of the PremUP program (foundation for scientific cooperation, www.premup.org), promoting translational research in perinatology It will profit specifically from PremUp technical platforms such as the Placental Physiopole and the imaging platform PremIMAGE, from the task force of the PemUp clinical and research network involving 20 000 births per year, and from well-characterized collections of biological samples (Equipex, Perinat Collection). Our project will be developed in collaboration with the "Pregnancy & Prematurity" teams of the PremUp network, including research teams (INSERM, CNRS, INRA) and care teams in the Paris region (maternity and paediatric units, AP-HP), allowing interactions with clinicians. Active collaboration with obstetric units (Cochin-Port Royal, , Robert Debré, CHIC

  Since 2007, the U767 was in charge and directed : 11 doctoral fellows (Doctoral school ED157 -Génétique, Cellulaire, Immunologie, Infectiologie et Développement), 3 "INSERM welcome (for clinicians)" positions, 18 Master's (3 M1 and 15 M2) research students, 3 BTS and 3 Licence pro. The day-to-day supervision of the PhD students is well done. Most of the researchers or teaching-researchers (PU, MCF, PU-PH, MCU-PH) are involved in teaching with participation in several Master programs. The unit is involved in several following research courses: -Reproduction and Development (University Paris 5 and 7); -UE Vascular Physiology and Pathology: regulation of angiogenesis (University Paris 6); -Cell Biology, Physiology and Pathology (University Paris 7); -Scientific seminar in Intra-uterine Growth Retardation for midwives and obstetricians (University Paris 5); -Training for adults : biotechnology and cell biology technicians (GRETA de Massy).

5

  Statistics by field: SVE on 10/06/2013

  of the Human Placenta Re.: comments relative to the AERES report D2014-EV-0751721N-S2PUR140006289-002011-RT Paris, April 20, 2013

Grades 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%

Pathophysiology & Pharmacotoxicology of the Human Placenta, Université Paris Descartes, Inserm, Mr Thierry FOURNIER

 Supervising bodies' general comments

Créteil,Kremlin Bicêtre, Antoine Béclère, Armand Trousseau)) will allow us to obtain human placental tissues and blood samples, with the patients' informed consent. This project will take place on the site of the Faculty of Pharmacy Paris Descartes and will benefit from the technical equipment and expertise of members of Paris Descartes IMTCE: confocal and electronic microscopy (B. Saubamea, IMTCE), and mass spectrometry (O. Laprévote, IMTCE). In addition, we have developed collaborations with teams specialised in proteomics (F. Guillonneau), FRET (P. Vincent), and gap-FRAP (J. Dompierre). This project will also benefit from our active participation in networks that include many laboratories working in the field (Nuclear receptors group, Peroxysomes & PPARs association, International Francophone placental Group (GfP), French cAMP network (club AMPc), which will share scientific knowledge, techniques, approaches and tools. In addition, the Unit is in charge of the organization of the International Federation of Placental Association (IFPA) congress in September 2014. All together this will facilitate collaborations, translational research and international visibility.

3/ Concerning publications, we are currently publishing in specialized journals such as Placenta and in more generalist ones such as Endocrinology, Plos One, Am J Physiol, FASEB J and JCEM for the clinical aspect of our work. We will concentrate our effort to publish in higher ranked journal such as Embo J and JCI for fundamental and clinical studies, respectively.

Concerning the use of animal models: Due to the specificity of human placentation we have concentrated our effort on the development of original physiological models in order to mimic human placental pathophysiology as closely as possible. We have original in vitro models (primary cultures of human placental mesenchymal and trophoblastic cells isolated at different terms of pregnancy) and ex vivo models (human perfused placental cotyledon). The in vivo approach of our project will be considered in collaboration with Dr Chavatte-Palmer (INRA, RTRS PremUp foundation), who has developed a rabbit model of IUGR.


President Michel Cosnard

Michael Levin

Gudrun Rappold

Richard Trembath

Chairmen

In the name of Hcéres 1 : In the name of the expert committee 2

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

HCERES NOMENCLATURE

SVE2-1; SVE2-2; SVE2-3; SVE3-4; SVE5-1; SVE5-3.

SCIENTIFIC DOMAIN

The IHU Imagine is a pioneering centre for rare genetic diseases with the vision to integrate basic research into clinical practice. The core missions of the Institute comprise patient-focused research, innovative care, education and training and technology transfer. Imagine has organized itself into six thematic integrated care and research programs on rare diseases. Research activities are supported by several on-site core facilities and include experimental and clinical research platforms as well as the laboratory of medicine and pathology. Clinical resources are provided from the Necker-Enfants Malades Hospital.

UNIT WORKFORCE

GLOBAL ASSESSMENT OF THE UNIT

The Imagine Institute is a unique venture in Europe and also worldwide in linking a genomic focused research to the large patient base of rare paediatric diseases in the Necker Hospital. Groups within the Institute are world leaders in unravelling the genetic basis of childhood diseases. The overall scientific output of the Institution, compared to international standards, is outstanding. The Institute has published over 2,800 scientific papers in the last 5 years. More importantly, significant advances in the identification and functional characterisation of genes underlying genetic disorders in several fields have been made and preclinical and clinical trials carried out. International recognition of Imagine is shown by the participation in many European and international consortia and also by the fact that advanced ERC grants were obtained by 5 team leaders in the last 5 years.

The Institute has emerged as a global leading centre in bringing molecular genetics into clinical care, and for training young scientists in the field of molecular genetics. The program for the next five years is likely to make a major contribution to improved understanding and treatment of genetic diseases.

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 International evaluation and accreditation

INTRODUCTION

  HISTORY AND GEOGRAPHICAL LOCATION OF THE UNITThe IHU Imagine is a large research unit supported by Inserm and the University of Paris Descartes. It is located in the centre of Paris. In 2013, it was created by the merger of 23 research groups and currently houses 23 research laboratories, as well as several core facilities.MANAGEMENT TEAMMr Stanislas Lyonnet was appointed as director general of the research unit UMR1163 / IHU Imagine in 2015. He was the successor of Mr Alain Fischer and took office in July 2016.