Section des Unités de recherche
Report from the visiting committee
Research unit :
Génétique Moléculaire, Génomique, Microbiologie
UMR 7156
University Louis Pasteur – Strasbourg 1
February 2008
Section des Unités de recherche
Report from the visiting committee
Research unit :
Génétique Moléculaire, Génomique, Microbiologie
UMR 7156
University Louis Pasteur – Strasbourg 1
February 2008
Report of the expert committee
Research Unit:
Name of the research unit : Génétique Moléculaire, Génomique, Microbiologie
Label demandé : UMR
N° (in case of renewal) : 7156
Head of the research unit : M. Serge POTIER
Main University or School:
University Strasbourg 1
Other institutions and research organizations :
CNRS
Dates of the visit:
February 28th of 2008
2
Members of the visiting committee
Chairman:
Mr Bruno GOUD, Institut Curie, Paris
Experts:
Mr Claude BRUAND, INRA, Toulouse
MrAgamemnon CARPOUSIS, IBCG, Toulouse
Mrs Sylvie DEQUIN, INRA, Montpellier
Mr Alain NICOLAS, Institut Curie, Paris
Mrs Lorraine SYMINGTON, Columbia University, New-York
Mrs Denise ZICKLER, IGM, Orsay
Mrs Sylvie COURTOIS, Paris
Experts representatives of the committees in charge of personnel
evaluation (CNU, CoNRS, CSS INSERM, représentant INRA, INRIA,
IRD…) :
Mrs Annick JACQ, représentante de la section 22 du CoNRS
Mr Jean-Marc REICHART, représentant de la section 65 du CNU
Observers
AERES scientific representative:
Mrs Alexandra GRUSS
University representative:
Mr Philippe CARBON, Université Strasbourg 1
Research institutions representative:
Mrs Martine DEFAIS, DS CNRS
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Rapport du comité d'experts
1 z Short presentation of the Unit
The Unit was created on January 1st 2005 by the merger of two CNRS FRE (2326 and 2375). It is structured into
two Departments: « Microorganismes, Génomes, Environnement » located at the Institut de Botanique, and
« Génétique Moléculaire et cellulaire » located at the IPCB (at about 10 min walking distance from the Institut de
Botanique). Each Department is composed of 3 teams headed by University Professors (teams 1-3, Department 1) and
CNRS researchers (teams 4-6, Department 2).
The six teams comprise 23 scientists with permanent positions (17 Professors and Assistant Professors from
ULP; 6 researchers from CNRS), 13 permanent administrative and technical staff (ITA/IATOSS from ULP and CNRS), 3
post-docs, and 20 Ph.D. students.
The research Unit includes:
•
17 members with an HDR
•
17 members who have been Ph.D. advisor during the past 4 years
•
6 members who have been granted a PEDR
•
22 « publishing » according to AERES criteria / 23
•
20 Ph.D. students (withdrawal rate : 0%). 13 students were granted a Ph.D. since 2004. The average
length for a Ph.D. thesis was 40 months. Ph.D. fellowships included: 14 from the Ministery of Research
and High Education, 3 from the EU, 6 from the DGA, 5 from foreign governements, 1 BDI, 1 CIFRE, and
3 from the « Region Alsace »
2 z Execution of the visit
The visit lasted for one full day, but started the day before with an informal discussion and a dinner gathering
the Director, the group leaders and the committee members. The committee listened to an overall presentation by
the Director of the Unit about history, scientific strategy, human, technical and financial resources, fit within the
institutional and industrial environment, and governorship. Each group leader gave a formal presentation in the
presence of the members of the whole Unit. Two poster sessions organized at the two sites where the Unit is located
were presented by students, post-docs and young scientists and gave the committee a good overview of the research
projects. The committee had two separate meetings with most of the students as well as representatives of the
permanent staff scientists, technicians and engineers. The committee then deliberated in plenary session in the
presence of representatives of the Institutions (CNRS and ULP) supporting the Unit.
3 z Global analysis of the Unit, of its evolution, and of its position
at the local, national and european levels
The Unit has produced about 100 publications in peer-reviewed journals during the 2004-2008 period, including
high-profile journals of general audience (Nature, Mol Cell, Genes Dev) and the best or very good journals of the
specialities represented in the Unit (Mol Biol Cell, Hum Mol Gen, Traffic, Yeast, J Bacteriol). Team leaders have been
regularly invited to national or international conferences.
4
The present organisation results from a deep restructuration that took place over the past 4 years. In 2002, the
teams of Department 1 have reoriented their projects towards comparative genomics and genome evolution of
hemiascomycete species (team 1) and environmental microbiology (Team 2) which led to the creation of two
independent teams in January 2006 (teams 2 and 3). This reorientation was supported by both ULP and CNRS. In
Department 2, a new team has emerged, being supported by a CNRS ATIP programme since 2005 (team 6).
The Unit is very well-integrated locally, and especially within the University. The Director of the Unit is
currently Dean of the Faculty for Life Sciences ; Professors and Assistant Professors coordinate several teaching
programmes (master and bachelor specialities). One group leader (team 2) is involved in a programme that gathers
twenty-two teams of the « Region Alsace » (programme « REALISE »). Two group leaders (teams 1 and 3) are in charge
of two GDR at the national level (GDR 2354 « Genolevures » and GDR 2909 « Métabolisme de l’arsenic chez les
procaryotes). Two group leaders (teams 4 and 5) have contributed or contribute to european networks (« MitEURO »,
2002-2006, team 4 ; RTN Marie Curie « Penelope », 2007-2011, team 5). Overall, the Unit has a good visibility at the
local, national and international levels.
4 z Evaluation team by team
Team 1 : « Evolution des génomes des microorganismes »
This team is composed of seven permanent staff scientists from ULP (2 PREX, 1 PR2, 4 MCF), two technicians (1
TCS CNRS, 1 AT ULP) and three Ph.D. students. The focus of this team is to study genome evolution using the
hemiascomycetes fungi as a model system. There are two main areas of investigation: comparative genomics and
creation of genetic assays to study gene duplications and gene loss in Saccharomyces cerevisiae. The progress during
the last four years was outstanding, particularly in light of the high teaching demands of most of the permanent team
members. A major achievement was an article in Nature (2004) resulting from a collaborative effort pioneered by the
team leader comparing genomes of representative species from the hemiascomyetes fungi. Major genome remodeling
events, such as massive and local duplication events, and reduction of genome size, are definitively at work during
evolution. In addition, several published studies made use of a clever genetic assay to detect gene reactivation
demonstrating that reversion can occur by a wide range of chromosomal rearrangements, including retrotransposon
insertion, deletion, segmental duplication and chromosome translocation. The spectrum of events was altered in
diploids compared with haploids, presumably because rearrangements that are haplo-lethal can be recovered in
diploids. The study of diploids is justified because most yeasts are naturally diploid and studies of genome
rearrangements by other labs have focused on haploids.
Future studies are aimed to (1) complete DNA sequence analysis of additional species representative of each
clade within the hemiasomycetes to further characterize the genome organization and evolution of these species,
with particular reference to gene duplications and the types of genes lost or gained between species. Further, to
pursue the reconstitution of the evolution of hemiascomycete species and develop tools of genome annotations,
within the excellent context of the “Génolevures” consortium. (2) To further study the various mechanisms for
chromosome rearrangements, genetic control of these events and the effect of ploidy using the well-characterized
ura2 reversion assay and a new genetic assay to characterize gene loss (3) To use the rearranged strains to address
the important issue of the molecular processes involved in genome incompatibilities and en-route speciation, and to
analyze the global consequences of different classes of rearrangements by transcriptional profiling.
The methods proposed are appropriate and the team is expected to make significant progress towards the
stated goals. The committee fully supports the proposed research lines. It also recommends: (1) a more systematic
analysis of different Saccharomyces cerevisiae isolates as performed for the DUP240 family, (2) the development of
functional “experimental evolution” approaches, integrating quantitative trait and fitness analyses, and (3) the
purchase of equipment for “in house” high throughput sequencing that will ensure the genome-wide view and boost
the competitiveness of the team.
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Team 2 : « Adaptations et interactions microbiennes dans l’environnement »
This team was created in 2002 on the basis of a CNRS-ATIP development award in fundamental microbiology to
the group leader. The group formed by the merge of three preexisting groups. In 2006, one of these groups
dissociated and became independent to give Team 3. The team is now composed of five permanent staff scientists (1
PR1 ULP, 3 MCF ULP, 1 CR1 CNRS), two technicians (1 T ULP, 1 AT ULP), and four Ph.D. students. The research project
centers around the topic of environmental microbiology, one of the new scientific axis of the Unit, with three main
themes i) degradation of, and adaptation to, halogenated pollutants (chlorinated methanes) by methylotrophic strains
(Methylobacterium), ii) characterization of a new tetrachloromethane-degrading strain isolated from a contaminated
area, iii) role of bacteria in the alteration of various materials.
In the 4 year evaluation period, Team 2 invested a lot in the organization of the lab, development of this new
topic, and in teaching activities through the setting up of a new curriculum linked to this environmental theme.
Although a number of good scientific contributions have been made, most of the production of the team is based on
work initiated prior to the creation of the group, on molecular adaptation/genomic plasticity in Lactobacillus
plantarum, and iron metabolism in Pseudomonas (~ 13 and 22 publications, respectively). These two topics have
progressively stopped, due to the retirement of one scientist and the reorientation of another towards the main topic
of the group. The number of publications related to this topic is still very low. However, given this refocusing of the
team’s members, the several new approaches that have been initiated, and the previous expertise of the group leader
in the bacterial metabolism of halogenated C1 compounds, it is the hope of this committee that productivity will
increase rapidly.
In addition to its reorientation efforts, the dynamism of the group is visible from the number and diversity of
its local, national and international collaborations, its various sources of funding, and its involvement in different
research networks. Of particular interest is the part taken by the group in an international network of collaborations
on annotation and comparative and functional genomics of eight Methylobacterium strains adapted to diverse
environmental conditions. This collaborative project could potentially lead to high quality publications.
It is clear that the pertinent environmental aspects of the topic, together with the numerous existing
collaborations of the group, will create new projects, generate new contracts and attract new people to the group.
However, care should be taken not to dilute the efforts by initiating too many different subjects. The committee
therefore strongly recommends focusing on a limited number of projects with clearly defined strategies and scientific
objectives.
Team 3 : “Ecophysiologie moléculaire des micro-organismes”
This team, which studies bacterial arsenic metabolism, was officially created only recently, in 2006. However,
the group of researchers of this team was previously part of Team 2, and the “arsenic” theme has been actively
developed since 2000. Currently, the group is composed of four permanent staff scientists from ULP (2 PR1 and 2
MCF), one post-doc, five Ph.D. students and one technician (TCN CNRS). The team leader has a leading role in a
French network of labs working on arsenic (GDR), and the team has published in the four years period, eight articles
on this topic in international journals, in addition to a number of articles by various members of the lab on other
subjects.
Initial focus on the metabolism of the new species Herminiimonas arsenicoxydans, capable of oxidizing
arsenite, has led to the identification of the operon responsible for oxidation of arsenite into arseniate. Current
research that will be expanded in the future is the functional genomics of H. arsenicoxydans (whose genome has been
recently sequenced by the GDR under the coordination of the team leader), including regulation of arsenic
metabolism. The group wishes to expand this research toward an exploration of the diversity of arsenic metabolisms
in contaminated ecosystems, using metagenomic and metaproteomic approaches, as well as comparative genomics
relying upon several sequenced genomes, including those of Thiomonas strains. One aim of the project is to develop
methods for water decontamination through bioremediation.
The various approaches developed by Team 3 are consistent with the aims of the project. Genomic studies are
likely to open up new avenues and bring results, which will broaden the previous, more focused studies on the
oxidation of arsenite by H. arsenicooxydans. The prospect of exploring the biodiversity of bacterial arsenic
metabolism is especially interesting. The new projects received ANR funding in 2007.
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Team 4 : « Transport mitochondrial d’ARN et maladies mitochondriales »
This group is composed of three permanent staff scientists (2 DR2 and 1 CR1 CNRS), one post-doc, one
technician (TCS, CNRS) and three Ph.D. students. The principal theme of research is the transport of RNA into
mitochondria. Although most proteins in the mitochondrion are encoded in the nucleus, synthesized in the cytoplasm
and transported into the organelle, the rRNA and tRNA components of the translational apparatus of the
mitochondrion are encoded in the mitochondrial genome and synthesized in the organelle. This group is at the origin
of the surprising discovery that a cytoplasmic lysyl-tRNA species is imported into the mitochondrion of yeast. Over the
past four years, the group has made significant advances in elucidating the mechanism of tRNA uptake. This process
involves the glycolytic enzyme enolase, which is associated with the outer membrane of the mitochondrion, and the
precursor of the mitochondrial lysyl-tRNA synthetase, which is believed to act as a carrier for the import of the
cytoplasmic lysyl-tRNA. Other work has demonstrated that the import of the cytoplasmic lysyl-tRNA is important for
translation in the mitochondrion at temperatures above 30° C. In the absence of lysyl-tRNA import, translation is
impaired at high temperature due to a defect in the endogenous lysyl-tRNA involving a chemical modification
necessary for reading AAG codons. This work suggests that the importation of the cytoplasmic lysyl-tRNA might be an
adaptation to growth at high temperature. Interestingly, the group has demonstrated that human mitochondria also
have a pathway permitting the importation of tRNA and 5S rRNA. In humans, genetic defects in the mitochondrial
genome affecting the translation apparatus are often associated with myopathies and neuropathies. In a specific
example involving a defective human mitochondrial tRNA, the group has demonstrated in cultured cells that
mitochondrial function can be restored by introducing a gene into the nucleus which expresses a functional tRNA that
is imported into the mitochondria. Ongoing research involves three directions: (i) the continuation of the work on the
elucidation of the mechanism of RNA import, (ii) understanding the role of the imported tRNAs, and (iii) the
development of new tools for treating human diseases by strategies involving the import of RNA into the
mitochondrion. The research of the group has been supported by a variety of grants including, most recently, funding
by the ANR on the project aimed at treating human diseases. During our interview of the members of the group, their
enthusiasm for the research project was fully evident. The leadership of the group is dynamic (steering committee for
MitEURO and co-organizers of several workshops) and appears to be very well organized. The scientific productivity of
the group in terms of published work is excellent (9 papers in high-impact factor journals) and the proposed research
for the next four years is well planned and ambitious.
Team 5 : “Cytosquelette d’actine et trafic intracellulaire”
This team is composed of two permanent staff scientists (1 DR2 CNRS and 1 MCF ULP), one technician (TCN
CNRS as of 5-2008) and two Ph.D. students. Two Post-docs (ANR and Marie Curie) will join in 2008. The team interests
are rather broad, extending from several aspects of actin-cytoskeleton organization in budding yeast to intracellular
trafficking. Nine papers (among which five as collaborators) and two reviews were published since 2004. Actin
organization is a tightly regulated process that co-ordinates complex cellular events but the molecular mechanisms
underlying these processes are not well understood. Three actin cytoskeleton associated SH3 domain proteins were
analyzed and will be exploited further in the next four years, along with other SH3 domain proteins : (1)
Bioinformatics-based research (in collaboration with O. Poch, IGBMC) through 20 genomes allowed a new alignment of
ARPs, which should now be fully exploited. (2) Involvement of the SH3-containing proteins in actin polymerization was
analyzed using in vitro actin polymerization assays on GST-SH3-coated beads. The interactions between SH3-domaincontaining proteins in different yeast species (a global interactome) will be developed through a Marie Curie Network
of young researchers. (3) Verprolin Vrp1 the yeast ortholog of the Wiskott-Aldrich syndrome interacting protein
(cytoskeletal regulator) and its interaction with Hof1/Cdc15 was found essential for cortical actin polymerization,
cellular growth and fluid phase endocytosis in cell extracts. Two additional projects include analysis of the nuclear
actin (in collaboration with two Japanese laboratories) and the development of new tools (photo-labile caged
fluorophores; in collaboration with M. Goeldner, Illkirch) for monitoring the dynamics of cytoskeletal proteins in
vesicular traffic.
The research plans are solid and worth undertaking. However, despite extensive collaborations through several
grants (ANR and European RTN), the team is and will remain rather small and the field extremely competitive: we
therefore recommend that this team focuses its attention on one or two subjects or identify a unique niche where
competition would be less strong.
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Team 6 : « Trafic membranaire et signalisation lipidique »
This team is composed of one permanent staff scientist (CR1 CNRS), one post-doc, three Ph.D. students and
one technician (IE CNRS). It is supported by a CNRS ATIP programme since 2005. Past work of the team has focused on
molecular mechanisms underlying the biogenesis of pre-lysosomal compartments MVBs (“Multivesicular bodies”) in
yeast S. cerevisiae. In particular, they have investigated the role of two phosphoinositide-binding proteins, Ent3 and
Ent5 and a new partner, Vps76, in this process. This study shows that Vps76, in association with Ent3/5 and the
ESCRT-0 complex, is involved in protein sorting at MVBs. The main plan of the team is to go on with the
characterization of the protein machinery and the role of phospholipids in endocytic trafficking, both in yeast and
mammals, a field in which the team leader has acquired a solid expertise. Others projects centered around the use of
yeast as a model system for functional characterization of proteins involved in the endocytic pathway and lipid
signaling, are developed in collaboration with other groups. They include the cellular role of MTM1, a phosphatase
mutated in X-linked myotubular myopathies (supported by an ANR grant in 2007), and the function of HIV-1 protein
Nef.
There are no publications as a group yet. However, three manuscripts have been submitted. This team is very
dynamic and appears to be well integrated in the Unit. The proposed studies address important questions in cell
biology around protein/lipid interactions and the formation of intracellular organelles. The only concern of the
committee is that the team leader should be cautious about developing too many projects and collaborations at the
same time, which may diminish the team’s performance in a highly competitive environment.
5 z Analysis of the life of the Unit
•
Management :
The overall management is satisfactory. All the teams recognize the leadership of the Heads of the two
Departments (who are also chairman and vice-chairman of the Unit) and are willing to work together. The general
assembly of the laboratory council voted unanimously (minus two abstentions) for the proposed Unit project.
Permanent scientists, administrative and technical staff, as well as Ph.D. students (Department 1) complained about
slowness of purchasing procedure for consumables and equipments, but the committee did not feel that a specific
problem exists within the Unit.
•
Human resources :
They are globally satisfactory. Each team has at least one technician/engineer. Students are numerous and
appear to be motivated and happy to work in this Unit.
•
Communication :
Being located on two sites does not facilitate communication between the two Departments, although this does
not seem to be a major problem for the moment. The communication between the teams, and between teams and
the Direction is satisfactory. ITA/IATOSS representatives were mainly concerned about career progression. The
committee felt that part of the problem could result from a lack of information and possibly support from the
Direction.
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6 z Conclusions
After individual evaluation of the teams, a frank and open discussion between members of the committee led
to the following conclusions :
—
—
—
Strong points :
•
The overall quality of research is very good, especially taking into account the fact that the
majority (17 out of 23) of permanent staff scientists have heavy teaching duties. Two teams (1
and 4) can be considered as leaders in their research areas.
•
The important restructuration of the Unit accomplished within the last 4 years has led to the
emergence of two Departments having a good visibility in their respective fields. The thematics
developed in each Department are different (genomics and evolution versus molecular and cell
biology), but the committee is expecting that more links will be established between the teams
in the near future. Some collaborations already exist based on shared technological and
methodological approaches linked to the use of yeast as a common model system. The teams
appear ready for more conceptual collaborations that should be favoured by their belonging to
the same Unit.
•
Teaching provided by Professors and Assistant Professors appears to be of excellent quality,
which explains that the Unit is able to attract many students (20 at present).
What needs to be improved :
•
Team 2 members are not focused on the present scientific project, but rather have continued
on previous topics.
•
The scientific project of Team 5 lacks focus.
•
The overall number of post-docs, and especially foreign post-docs, is low.
Recommendations :
•
The committee feels that the Unit now needs mainly time and stability to develop research
projects after a successful restructuration.
•
Nevertheless, key members of the Unit, including the vice-chairman and two group leaders are
expected to retire within the next 5-6 years, and the Unit should already prepare to organize
their take over and to attract new teams.
•
Teams 2 and 5, and to a lesser extent team 6, should be more focused on a limited number of
projets.
•
Effort should be made to attract foreign post-docs.
•
The communication between the two Departments could be improved by the organization of
joint seminars on a regular basis.
•
Attention should be made to better inform and possibly support within the Unit, the career
progression of administrative and technical staff.
•
Most of the Professors and Assistant Professors work in Department 1 whereas teams of
Department 2 concentrate the majority of CNRS researchers. This situation could be improved
by the recruitement of CNRS researchers in Department 1 and Assistant Professors in
Department 2.
•
Recurrent financial support from the CNRS should be significantly increased.
•
To locate the Unit on one site would improve its overall organisation.
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GÉNÉTIQUE MOLÉCULAIRE,
GÉNOMIQUE,
MICROBIOLOGIE
UMR 7156
FICHIER 2 : VOLET GÉNÉRAL (à annexer au rapport rendu public)
The following aims to provide complementary information relevant
to the section « what needs to be improved » page 9.
Serge POTIER
Professeur
Directeur du Laboratoire
Faculté des sciences
de la vie
Institut de botanique
28 rue Goethe
F-67083 Strasbourg Cedex
Tél. : (33) 03 90 24 18 13
Fax : (33) 03 90 24 20 28
www-ulp.u-strasbg.fr
[email protected]
Team 2 : “team 2 members are not focused on the present scientific
project, bur rather have continued on previous topics”
The diversity of research topics presented by Team 2, noted as
excessive by the Committee, should be considered as a testimony of
the structuration efforts undertaken for the creation of a team in
environmental microbiology at ULP, as wished by CNRS upon
recruitment of the team 2 leader in 2002. The efforts to link different,
unrelated research topics in the former Unit FRE2326 to stimulate
interactions between Unit members will now be documented by several
manuscripts, submitted or in preparation.
Of course, the research potential found today under the banner
"genomics of C1 halogenated compounds" is now such that work of
team 2 is already almost exclusively devoted to this subject, as indeed
recommended by the Committee. In other words, team members are
mainly focussed on this core research topic, as underlined by novel
experimental approaches of the subject which have recently emerged.
In this context, the willingness of several permanent staff
members of the original FRE2326 to change and/or extend fields of
research deserves explicit mention in our view, since this has been at
the expense of a more extensive publication activity for them in the
immediate short term.
Team 5 : “The scientific project of Team 5 lacks focus”
The team recognizes that its subject "Actin Cytoskeleton and
Intracellular Traffic" involves a complexity of numerous proteins for
outside reviewers and takes this opportunity to ask for rectification of a
number of errors in the evaluation text (see erreurs matériels) and
resulting confusion which they feel have reflected negatively on the
team's evaluated performance and objectives. In a small group
situation, the team leader's politics of international collaboration was an
essential choice that allowed us to make significant contribution with
international publication for each aspect of actin function addressed.
We appreciate the concern of the committee for an apparent dispersion
of topics in a small group. However, we emphasize the word apparent
and hope that the evaluation experts will agree that all aspects of our
project address the global function of actin. Current work on nuclear
actin function is a long standing solicited collaboration where results
progressed slowly as a secondary project but which are now exploited.
One article is in revision and a second one is being written to finalize
this project. The bioinformatics analyses are now well exploited since a
publicly accessible web site created with ARP analyses in 2005 is
frequently consulted and regularly updated.
Our project is now centered on the role in actin polymerization
and traffic of SH3 domain-containing proteins including the
determination of SH3 domain interactomes, supported by the RTN. The
proteins studied in the group are actin cytoskeleton associated and
involved in endocytosis, essentially through their SH3 domain
interaction with proline-rich activators of actin polymerization, such as
yWASP/Las17p and yWIP/Vrp1p. Functional analyses of the SH3
domain proteins of unknown function called Lsbs (for Las seventeen
binding), which we were the first to identify several years ago, are
currently being investigated as thesis subjects. In answer to the critique
of the group being and remaining small despite extensive collaborations
in several grants (two currently), we ask the committee to note that the
European RTN grant actually started less than a year ago. An RTN
doctoral student started in 2007, a post-doc has been hired starting in
May and the EU consortium has awarded us a second doctoral bursary
for 2008-2011. The ANR has just started, an interdisciplinary R&D
project to develop new tools for intracellular dynamics in which we will
use actin and its cellular partners as proof of principle. A post-doc will
be recruited for the biological aspects. Our collaborative work on this
subject has resulted in a recent publication, Orange et al. Chem
Commun. 2008,1217-1219. This article was very recently selected for
inclusion in the Chemical Biology Research Articles virtual journal, a
selection among 15 journals for articles of highest general interest.
We hope that these explanations of our current and planned
research activities will persuade the committee that our scientific project
is focused and to modify its conclusion that the scientific project of team
5 lacks focus (p9 what needs to be improved and in recommendations).
./.