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					               Section des Unités de recherche




Report from the visiting committee
Research unit : Myology Group – UMR_S 787
University Pierre et Marie Curie - Paris 6




                       February 2008
               Section des Unités de recherche




Report from the visiting committee
Research unit : Myology Group – UMR_S 787
University Pierre et Marie Curie - Paris 6




                       February 2008
Report from the visiting committee

The research unit :
    Name of the research unit : Myology Group

    Requested label : UMR_S

    N° in case of renewal : 787

    Head of the research unit : Mr David Sassoon




University or school :

    University Pierre et Marie Curie - Paris 6




Research organization:

    INSERM




Date(s) of the visit:

    February 11th 2008




                                                   2
Members of the visiting committee

  Chairman of the commitee :
  Mr Laurent SCHAEFFER, Lyon




  Other committee members :
  Mr Kevin P. CAMPBELL, Iowa City IA, USA
  Mrs Anne HAREL-BELLAN, Villejuif
  Mr Ulrike MAYER, Norwich, UK
  Mr Peter W. J. RIGBY, London, UK
  Mr Stefano SCHIAFFINO, Padova, Italy
  Mr Volker STRAUB, Newcastle upon Tyne, UK




  CNU, CoNRS, CSS INSERM,                             représentant INRA, INRIA, IRD…..)
  representatives :
  Mr Claude FEREC, Brest, CSS INSERM representative
  Mr Laurent LESCAUDRON, Nantes, CNU representative (section 66)




Observers

  AERES scientific representative :
  Mr Bruno GASNIER




  University or school representative:
  Mr Jean CHAMBAZ, University Pierre et Marie Curie - Paris 6




  Research organization representative :
  Mrs Chantal LASSERRE, INSERM




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Report from the visiting committee


      1 Short presentation of the research unit
      Total number of lab members : 37, including

           •    1 researchers with teaching duties

           •    4 INSERM full time researchers

           •    18 postdocs

           •    11 engineers, technicians and administrative assistants

           •    3 PhD students including 2 with a fellowship

      Number of HDR : 2 ; number of HDR who are PhD students avisors : 2

      Numbers of PhD students currently present in the research unit : 2

      Numbers of “publishing” staff researchers with or without teaching duties : 4 out of 5




      2 Preparation and execution of the visit
     The visit of the two myology units from University Pierre et Marie Curie was performed by (almost) the same
committee, and on two consecutive days : Day1, Myology Group UMR_S 787 ; Day 2, Unit ‘Diseases of striated muscle’.

      Day 1 :

           •    10h-10h30 : Review committee time

           •    10h30-11h00 : Overview of Unité by the director

           •    11h00-12h00 : Presentation of Team 2 by its leader

           •    12h00-12h45 : Presentation of Team 4 by its leader

           •    13h00-14h00 : Lunch with students/postdocs (Two large teams from the Myology Group were not
                represented because they will join the ‘Diseases of striated muscle’ in 2009. Possible opinion
                divergences between the departing groups and the others were thus not possible to evaluate at this
                occasion).

           •    14h15-15h00 : Presentation of Team 1 by its leader

           •    15h00-15h45 : Presentation of Team 3 by its leader

           •    15h45-16h30 : Visit of lab space facilities

           •    16h30-18h30 : Committee deliberation

           •    18h30 : Debriefing by the chairman of the committee




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       3 Overall appreciation of the activity of the research unit, of its
         links with local, national and international partners
           •    Preliminary comment :

      The site of the Pitié Salpêtrière hosts two laboratories working on skeletal muscle hereafter designated as Unit
1 (“Myology group”, UMR_S 787) and Unit 2 (“Diseases of striated muscle”). These units were evaluated on two
consecutive days by the committee.

        Unit 1 was created 18 months ago, a period during which working conditions were not optimal since the space
allocated to them (about 800 m2) was undergoing renovation. Therefore, scientific production from this unit is
difficult to evaluate since much of the work presented was performed in the former laboratories of the group leaders
(see evaluation of individual teams).

        The unit is very active in terms of national and international collaborations. It is involved in European networks
and is funded by many sources including ANR, AFM and NIH.

       Teams 1, 2 and 4 have an international reputation, attested by their collaborations with excellent foreign
laboratories. Team 3 just started 10 months ago.

       The composition proposed for the unit is of four Teams. Teams 1 and 2 were already present in the former
unit. Teams 3 and 4 were recently recruited and will replace two teams that will join Unit 2 in 2009. The latter were
evaluated with Unit 2.

       Teams 3 is led by a young cell biologist dedicated to the study of the mechanisms through which cytoskeleton
controls the position of nuclei in cells. The committee considered that the recruitment of this group was a bet and a
“smart move”, since this topic is very timely for many neuromuscular diseases, not mentioning the fact that this team
brings top quality imaging techniques to Unit 1. Groups studying myopathies with central nuclei at Pitié Salpêtrière,
including Team 4 of Unit 1 and Team 1 of Unit 2, should greatly benefit from the input of this fundamental research,
and vice versa.

       Team 4 is presently a member of Unit 582 (Unit 2). It is led by a young scientist and clinician with a solid
experience in early onset myopathies. The focus of this group is closely related to the approaches developed in Unit 2,
however its affiliation to Unit 1 and the proximity with Team 3 will be mutually beneficial for identifying mechanisms
underlying these diseases.




       4 Specific appreciation team by team and/or project by
         project
       Team 1: Stem Cell and Muscle Biology

       This group arrived from New York almost two years ago to create a laboratory in the building of the University
Pierre et Marie Curie at 105 bvd de l’Hôpital.

       The group is composed of 1 INSERM research director, 8 contractual researchers and one contractual engineer.
The co-director of the group has not obtained a permanent position yet. Due to the pivotal role of the co-director in
running of the team, this constitutes a serious problem for the group.

       The group is extremely well funded since the leader has been awarded a senior “Chaire d’excellence”
(500 000€) and still benefits from its NIH and MDA grants. It is involved in a European network (Optistem)

       The main topic of the group is the study of PW1, a protein they initially isolated from a screen designed to
identify novel regulators of early stem cells. Further characterization revealed that PW1 was involved in the p53,
NFkB and TNFα pathways, thereby suggesting that p53 and PW1 might be involved in muscle atrophy. In postnatal
muscle, PW1 expression is restricted to satellite cells and interstitial cells, which might correspond to mesangioblasts.
The work of the group is a good example of basic research that could be rapidly transferred and integrated with
human biopsies.

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        A major challenge of the group is to realize the conditional inactivation of PW1 to investigate its functional
role in stem cell populations and in muscle atrophy. This will be a major issue because it should allow determining
whether PW1 is an actor rather than a marker in stem cells. Further characterization of PW1 positive interstitial cells
is also an important issue. In particular, it will be important to determine if they correspond to the mesangioblasts
described by a group from the San Raffaele Scientific Institute (with whom Team 1 collaborates) or to the AC133 cells
described by Team 2 of Unit 2.

       The group has produced excellent scientific papers in Genes and dev. (2006), Development (2004), and Nature
Structural biol. (2002). They are also very collaborative has illustrated by their association to numerous collaborative
papers.

        The last paper of the group was published in the excellent journal Genes & Dev. in 2006. Therefore the
scientific production of the group in Paris is difficult to evaluate since all the data published were produced in their
former laboratory. As mentioned above, the laboratory has undergone renovation for the last 18 month, which did not
facilitate the work.



       Team 2 : Mouse Molecular Genetics Group

       The group is composed of one INSERM research director, seven post doctoral fellows, one M2 student and one
contractual technician.

       This young Inserm Avenir group is very well funded (ANR maladies rares, Inserm Avenir program, AFM). Its
leader is a young, extremely dynamic and productive researcher. The different projects developed in the group are
coherent with previous activities of the group leader, who is already a renowned expert in early muscle development,
particularly for his contribution to the study of the roles of Pax genes during development.

      The group has developed a very elegant approach to purify myogenic population in vivo to analyse the
molecular networks involved in these cells using a microarray approach. This work will undoubtedly generate
important data, and allow this group to remain at the leading edge of muscle development.

        The group also develops new strategies to investigate cell cycle arrest in muscle cells during development by
conditionally inactivating cell cycle regulators, and molecular pathways downstream of Pax factors using an evo/devo
approach. The group is less skilled in these topics, and the outcome is less predictable. The group leader will have to
pilot these approaches carefully, and to evaluate soon enough their viability on the long run.

       Finally, the group has generated mouse models for the Waardeburg syndrome, a rare genetic disease
associated with craniofacial defects due to mutations in Pax3. The mouse lines are already generated and initial
results are very promising. In addition to their medical interest, these models will allow to address developmental
questions in craniofacial morphogenesis and ectoderm and neural crest derivates.

        A technical point was raised: the success of the project will depend on the development of an efficient animal
facility on site. The laboratory is conscious of the problem, which is currently being addressed.

       Up to now the scientific production of the group leader in his former lab has been outstanding, but the
evaluation of the productivity of the group as an autonomous team is not yet possible since it is very recent. However,
given the quality of the projects currently developed, the committee is confident that the group will meet the
standards of scientific excellence.

      The committee considers that it would be a real chance for PhD students to be supervised by such excellent,
imaginative and dynamic group leaders starting their group, and that Team 2 should therefore recruit PhD students.



       Team 3 : Cytoskeleton architecture and cell polarization

       This team has been created a few months ago with the recruitment of a young cell biologist dedicated to the
study of nuclear positioning in the cell. The group leader has been awarded an Inserm Avenir position, and the team is
currently composed of two postdoctoral fellows and one PhD student. The group leader has decided to apply his skills
in nuclear position study to muscle cells differentiation and migration. The development of this topic is timely and fits
extremely well with the environment of the two myology units where several groups study myopathies associated with
myonuclei misplacements. The study of the molecular determinants of nucleus position in muscle is an important issue

                                                                                                                       6
in myology and the work of Team 3 should be very beneficial to the community. Conversely, the groups studying the
pathophysiology of myopathies with central nuclei will provide very valuable models to this group. The committee
encourages this Team to invest more on the study of nuclear movements in patients’ fibroblasts and to investigate
myopathies more actively than proposed in the project. Collaborations with the laminopathies group of Unit 2 are
evident, and close contact should be established with the European network of laminopathies.

       This group brings excellent cell biology and very nice imaging techniques to the unit. The set up for microscopy
is very impressive. The laboratory will have to address the problem of the storage of huge amounts of data that will
be generated by this group.

       The viability of Team 3 is less certain than for the other groups, since the group leader is less experienced than
the others, and his main achievement up to now is the excellent paper he published in Cell in 2005 during his post
doctoral training. However, the discussion with the team leader clearly showed his scientific quality. He is a very
imaginative and dynamic scientist. His projects are focused enough to be achievable, and he manages his recently
created group efficiently.

     The scientific production of Team 3 cannot yet be evaluated because it was created 10 months ago, but the
committee considers that the project is excellent and timely, and should generate important data.



       Team 4 : Early-onset myopathies

        The team leader has a permanent researcher position at Inserm. She was formerly leading an Inserm Avenir
group dedicated to early onset myopathies (EOM) in UMR_S 582 (Unit 2) and plans to join Unit 1 in 2009. The team will
be composed of the leader, one clinical associate, one contractual researcher, and one contractual technician. The
team leader is also a neurologist and spends one day per week at the neuromuscular disorders consultations of the
Institute of Myology. The group has previously identified 4 genes responsible for 8 forms of EOM, and now proposes to
focus on the pathophysiological mechanisms of EOM in order to identify new pharmacological targets amenable to
design therapeutic strategies.

       The reasons of her affiliation to Unit 1 are motivated by the desire to be in close proximity groups working in
basic science. This will help her to develop more mechanistic studies underlying the pathophysiology of the diseases.
Her decision was further influenced by the opportunity to lead an independent research group, what would not be
possible if she would have joined unit 2. The committee felt that this choice was sound, because collaborations with
more fundamental groups will be crucial for the success of the new focus of the team. Conversely, the presence of
this group will provide the unit with a clinical vision, and will contribute to develop bedside to bench exchanges.
However, the committee felt that collaborations with the other groups of the unit, and what is expected from them,
should be more precise in the project. The committee further thought that it was timely, and a wise career move, to
take on responsibility as an independent group leader and strongly encourages her to do so.

       The committee notes that this small group proposes to develop many projects, which might be too many
considering the clinical activity of the group leader. The group should advertise to recruit, and focusing will probably
be necessary.

      The scientific production of the group has been good until now, and the future orientation towards more
fundamental aspects of pathophysiological mechanisms should benefit to the publication level.




       5 Appreciation of resources and of the life of the research unit
           •    Of the quality of the management:

       The young team leaders of the new unit rely on the director to manage the unit and deal with the budget.

       Funding is very comfortable and the space is sufficient for four young groups. Therefore, these groups are not
limited in their work and no conflicts were reported.

      Team leaders and people in charge of common facilities meet with the director every 4 months to discuss the
general running of the unit.


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           •    Of human ressources :

        The main criteria for the recruitment of new groups is scientific excellence in basic research related to the
field of myology. This policy seems to work well and will expand the techniques of the unit.

       Each group leader is in charge of the running of his/her staff. Each group is also involved in common duties.

        Technical staff is provided by MENESR (4), Inserm (3) and contractual (4) to assist the teams and run common
facilities.



       Of the communication strategy :

       One of the aims of the director is to create an open space environment to favour interchange and
collaborations. A huge open-plan laboratory space has thus been created to host the benches of the four groups in the
same room. This has so far proven to be successful and is indeed beneficial to communication.

       Several regular events are organized to favour scientific exchange :

           •    bi-weekly work-in-progress meetings where students and post docs present their ongoing projects
           •    bi-monthly technical meetings to discuss technical points over a coffee
           •    journal club dedicated to students and post docs. Senior researchers do not attend
           •    Speakers of Monday seminars have lunch with students/postdocs.
           •    “Classics”: papers before 1995 (not available on the web) presented by seniors to young fellows to
                provide them with a historical perspective.

       These initiatives are much appreciated in the laboratory and highly contribute to the dynamic of the unit. They
constitute an excellent training for the students and post docs.




       6 Recommendations and advice
            •   Strong points :

        This is a very dynamic laboratory, constituted of groups of excellent scientific quality. This dynamism is
facilitated by the enthusiasm of the director and of the young team leaders, by important funding and by the
recurrent scientific events. The ‘open space’ laboratory is an excellent initiative.
            •   Weak points :

       As stated in the introduction, the physical separation of this laboratory with the Institute of Myology is
regrettable, and although collaborations exist, it does not favour continuous exchange between clinical and
fundamental research. However, see recommendations below for the conditions and time frame for a successful
exchange.
            •   Recommendations :

       The groups of this unit contribute to create one of the best environments to study skeletal muscle, from
“bedside to bench”, in France.

       The two units evaluated by the committee work on very complementary topics, yet with different conceptions
and goals. The ‘Myology Group’ (Unit 1) unit is rather oriented towards fundamental myology, whereas the ‘diseases
of striated muscle’ unit (Unit 2) is rather oriented towards physiopathology and treatment of muscle diseases.
However, the separation is not that sharp. For example, Unit 1 has recruited a team which was formerly part of Unit 2
and is dedicated to the genetics, pathophysiology and treatment of early onset myopathies. Similarly, two groups of
Unit 1 plan to join Unit 2 in 2009.

      Overall, the committee has unanimously felt that it would be a great benefit to have Unit 1 and 2 working
together in the same building. However, the committee realized that at in the near future it was not possible to
achieve this goal, which should nevertheless remain a major issue to address in the long term.

        The question of the reasons that made that the creation of two, rather than one unit engulfing these two, was
also discussed. Obviously, in addition to the scientific rationale, the distribution of the groups between the two units

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has also been motivated by personal affinities or opportunities offered to the group leaders. It is also quite clear that
the visions of the two directors are different and that, up to now, attempts to create a single laboratory failed.

      The necessity to have one instead of two units was not considered to be a priority by the Committee, the
important goal remaining to favour the geographic unification of the units, to facilitate contacts between researchers,
postdocs and students. It is important to mention that active collaborations already exist between the groups of the
two units, and our recommendation is to reinforce and further develop the contacts between the groups.

       The complementarity between the two units also nicely illustrates the necessity to maintain basic research in
close contact with laboratories more dedicated to treatment, to feed them with new concepts and new avenues of
therapeutic investigation. This constitutes an absolute prerequisite to develop structures with long term viability.




                                                                                                                       9
                                                             Dr. David Sassoon, Director
                                                             UMRS 787-Myology Group
                                                             Université Pierre & Marie
                                                             Curie-Paris VI- INSERM
                                                             105 bd de l’hôpital
                                                             75634 - Paris (Cedex 13)
                                                             France
                                                             david.sassoon@mssm.edu




M le President POMEROL
Paris VI


                                               Paris, April 11 2008


Monsieur,

Please find herein the “responses” we have to the AERES report regarding
their visit to our Unité on February 11th of this year. The responses are
essentially minor as the report (we believe) is overall very positive and thus
we would only like that a few issues become clarified. We (myself as Director
and the Team Leaders) have gone over the report and thus our responses are
combined. This may be treated directly by AERES or made part of the
document.

With best wishes,




David Sassoon
Rapport d'évaluation de l'UMR S 787 –Director: David SASSOON
Volet-“Response”
         We are delighted with the general conclusions of the committee and we thank
the committee for their careful review and time spent during this process. As the
AERES report will serve as a critical tool for helping our newly created research Unit,
as well as serve as a guide to our partners at Paris VI and Inserm concerning
questions regarding space, logistic support, etc., we would like the following points
clarified if possible.

General comment 1 - Other than suggesting geographical unity in the long-term as
opposed to fusing the 2 units, nonetheless, a significant amount of text is devoted to
unit 2 in a review of unit 1. Our only concern is that when this text is published on-
line, it will lead to the misunderstanding that these units are not independent
structures one of which is being renewed (UMR S 787-SASSOON) whereas the
second is being proposed for creation.

General comment 2 - The ‘vision’ of Dr Sassoon was endorsed by the committee
and for this we are delighted. However, part of that vision presented to the
committee was the additional recruitment of young groups. As the AERES report is
to serve as a critical tool for our partners in financing and creating space for research
units (should they be approved), it is important to have a comment on further
recruitment proposed.

General comment 3 - It would be useful to have general recommendations from the
committee regarding space issues, since Team 4 is currently not located within the
Myology Group whereas 2 departing groups are currently located in the Myology
Group. Specifically, page 7, section 5, paragraph 2 – It is noted that “space is
sufficient for four young groups”, however the proposed unit is composed of 1 senior
+ 3 young teams, team 4 will only move in 2009, and Teams 3 and 4 will grow as
noted by the committee. Therefore, the space is sufficient if the departing teams
release the space they presently occupy.

General comment 4 – The committee raised the issue of the need to recruit more
Ph.D. students, specifically with reference to Team 2. Team 2 has currently an M2
student that should therefore start the PhD program in September 2008. The current
university policies do not allow teams to host more than one PhD student per DR
poste (1DR position = 1.5 PhD students). It would be helpful to us all if this policy
regarding limits of students was addressed.

Minor Comments:

1- The report notes that members of departing teams did not attend the lunch. This
appears (as written) to be an error on our part. We presented only members of the
teams moving forward for the next 4-year plan. It should be pointed out that on that
day, almost all members of the departing teams were busy preparing for their review
the following day.

2- (Team 1) page 5, section 4, paragraph 3, Chaires d’Excellence is cited as direct
funding for Team 1. While this award was made to Dr Sassoon (co-director of Team
1), we note that most of these funds were used to support re-equipping the Unit and
supporting other teams. This is important since the proposal for this grant made to
the French Government stated that the funds would be used primarily to equip a new
Unit.
3-(Team 1) page 5, section 4, paragraph 4, the reviewers cite the work on PW1 as
the main topic of the group. While accurate, it leads to the impression that the work
outlined in the proposal on p53, aging, skin, cancer, etc. are minor topics which is not
the case.

4-(Team 3) page 6, paragraph 12, the committee should note that Team 3 has
managed in the short time since arriving to the Unit to obtain significant external peer
reviewed funding from, MDA, la ligue, FRM and ARC and all the team members have
fellowships.

5- Page 7, (Team 4), paragraph 1, line 3: Team 4 is already composed of the leader,
a contractual researcher, 2 clinical associates, a contractual technician and 2 master
students, one of which will stay as a PhD student from September. An additional
postdoctoral researcher will join the group from May 2008. All these members will
join the U787. Further recruitment is indeed necessary and planned.