Roland LE BORGNE
Nationality: French, Born May 1969, PhD
Position: Group leader, IGDR, Rennes, France
Married, 3 children
link Google Scholar (list of publications and H index):
http://scholar.google.fr/citations?user=UyWpMfsAAAAJ&hl=fr&oi=ao
link OpenWetWare (web site of the team): http://openwetware.org/wiki/LeBorgne
1- Education
2006- Habilitation à Diriger les Recherches- Université de Rennes 1
1992-1995- Ph.D at EMBL,Heidelberg, Germany with Bernard Hoflack
2- Research experience
2006- present DR1 CNRS (since 2014), Group Leader
Institute of Genetics and Development of Rennes-CNRS UMR 6061-Rennes
AERES evaluation of the team (2011-2016): A+
1999-2005: Ecole Normale Supérieure, Paris, with F. Schweisguth
1997: Chargé de recherche CR2 CNRS
1996-1999: Ph.D at EMBL (Germany) and then Institut de Biologie de Lille (France) with B. Hoflack
3- Teaching M2 SCMV Université Rennes 1, 4 hours/year
IGDR PhD Program: 50 h/years lectures+practicals: training to nano-ablation and FRAP
4- Awards
ATIP grant-2006
Bronze medal of CNRS-2003
EMBO Ph.D Fellowship-1992
5- Evaluation of Research/ Committees-Panels
2007-2010 Member of the CNRS Scientific committee ‘Interface physique, biologie et chimie’
CNRS
2000-2013 Member of the ‘Commission d’Expertises Nationales’-La Ligue contre le Cancer
2005-2013- Referee on 4 HDR and 17 thesis committees
Since 2006: Evaluation of grants from the ANR programme Blanc, Italian Pasteur Institution,
Humbolt fundation
Since 2005: Referee for Nature, Nature Cell Biology, Development, Current Biology, Traffic,
Molecular Cell Biology, Science Signaling, Nature Communications, Molecular Biology of the Cell,
Journal of Cell Science
6- Participations to juries (2011-today)
2015- Thèse de Pauline Salis, IBDM, équipe Le Bivic (rapporteur)
2014- HDR Neetu Gupta, Institut Pasteur, équipe Israël/Echard (examinateur)
- Thèse Charlotte Besson, Institut Pasteur, équipe Schweisguth (rapporteur)
- Thèse Onur Kaya, IMP Vienna, équipe Knoblich (rapporteur)
- Thèse d’Emmanuel Gallaud, IGDR, équipe Giet (president)
- Thèse de Benoit Dehapiot, IGDR, équipe Halet (president)
2013- AERES committee CRBM, Montpellier, France, Directeur A. Debant
- HDR Manos Mavrakis, IBDML équipe Lecuit (rapporteur)
- Thèse P-M Le Droguen, Institut Jacques Monod, équipe Guichet (rapporteur)
- Thèse N. Tavernier, Institut Jacques Monod, équipe Pintard (rapporteur)
2012- AERES committee Laboratoire de Neurophotonique, CNRS/Univ. Paris Descartes, Directeur V.
Emiliani
- HDR G. Rabut, IGDR, équipe Prigent (examinateur)
2011- HDR J. Pécréaux, Institut de Génétique et Développement de Rennes (Président)
- HDR R. Rousset, Institut de Biologie Du Développement et Cancer, Nice, équipe Noselli (Rapporteur)
- Thèse J. Moretti, Institut Pasteur Paris, équipe Brou/Israël (rapporteur)
- Thèse B. Jauffred, Institut Curie, équipe Bellaïche (rapporteur)
- Thèse A. Vallée, IGDR, Rennes, équipe Galibert (examinateur)
- Thèse S. Simoes, Institut Curie-UMR 144, équipe Raposo (Rapporteur)
7- Publications
Statistics
30 research articles, 7 reviews and 2 dispatches
Cumulated citation records (1993-2015): 3007
H-index: 27 (http://scholar.google.fr/citations?user=UyWpMfsAAAAJ&hl=fr&oi=ao)
Publications 2011-today
1- Le Bras S. and Le Borgne, R. (2014) Epithelial cell division – multiplying without losing touch. J. Cell
Science Oct 24 jcs 151472 (Epub ahead of print)- Commentary
2- Cotton, M., Benhra, N., and Le Borgne, R. (2013) Numb inhibits the recycling of Sanpodo in
Drosophila sensory organ precursor. Current Biology 23 (7), pp 581-7.Comment in Current Biology
23 (7) R270-2
3- Founounou, N., Loyer, N. and Le Borgne, R. (2013) Septins regulate the contractility of the
actomyosin ring to enable adherens junction remodeling during cytokinesis of epithelial cells.
Developmental cell 24 (3), pp242-255. Cited in Faculty of 1000 Biology & comment in
Developmental Cell 24(4) 336-8
4- Hoffmann,C., Mazari, E., Lallet, S., Le Borgne, R., Marchi-Artzner, V., Gosse, C. and Gueroui, Z.
(2013) Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles.
Nature Nanotechnology 8 (3), pp 199-205
5- Beckett K, Monier S, Palmer L, Alexandre C, Green H, Bonneil E, Raposo G, Thibault P, Le Borgne R.,
Vincent JP. (2013) Drosophila S2 Cells Secrete Wingless on Exosome-Like Vesicles but the
Wingless Gradient Forms Independently of Exosomes. Traffic 14 (1), pp 82-96
6- Le Bras, S., Rondanino, C., Kriegel-Taki, G., Dussert, A. and Le Borgne, R. (2012). Genetic
identification of intracellular trafficking regulators involved in Notch-dependent binary cell fate
acquisition following asymmetric cell division. Journal of Cell Science 125 (Pt 20), pp 4886-901
7- Founounou, N. and Le Borgne, R. (2011) Tissue polarity: PCP inheritance ensured by selective mitotic
endocytosis. Current Biology 21 (18), R690-2 (Dispatch)
8- Benhra, N., Lallet, L., Cotton, M., Le Bras, S., Dussert, A., and Le Borgne, R. (2011). AP-1 controls
the trafficking of Notch and Sanpodo toward E-Cadherin junctions in sensory organ precursors.
Current Biology 21 (1), 87-95. Cited in Faculty of 1000 Biology
9- Burgess J, Jauregui M, Tan J, Rollins J, Lallet S, Leventis PA, Boulianne GL, Chang HC, Le Borgne R,
Krämer H, Brill JA. (2011). AP-1 and clathrin are essential for secretory granule biogenesis in
Drosophila. Molecular Biology of the Cell 22 (12), 2094-105.
10- Le Bras, S., Loyer, N. and Le Borgne, R. (2011) The multiple facets of ubiquitination in the regulation
of Notch signaling pathway. Traffic 12(2), pp 149-61 (Review)
8- International Conference-Lectures
2015 - EMBO Conference- The multidisciplinary era of endocytic mechanics and functions,
Mandelieu la Napoule, France, invited speaker
- The Notch meeting, Athens, organizing committee and invited speaker
- 14th EMBO endocytosis meeting-The multidisciplinary era of endocytic mechanics and functions,
Mandelieu La Napoule, France, invited speaker
- 56th American Drosophla Research Conference, Chicago, 1 talk selected from abstract,1 poster
2014 - The Notch Meeting Athens (Greece), invited speaker
- 19th The molecular and developmental biology of Drosophila-2014 Crete Drosophila meeting
(Chiana, Crete, 22-28th June), Selected Speaker
- Institut Albert Bonniot, Grenoble (France) invited by Corinne Albiges-Rizo
- IMP-Institute of Molecular Biotechnology, Vienna (Autria), invited by Juergen Knoblich
2013 - The Notch meeting (Athens), invited speaker
- Institut de Recherche Servier, invited by B. Lockart
- Gordon Research Conference, Cell Contact and Adhesion (Lucca, Italy), Talk (selection on
abstract)
- Institut Pasteur (Paris) Invited by A. Echard
- Centre de Biologie du Développement (Toulouse), invited by S. Plaza and F. payre
- Annual Drosophila Research Conference (Washington), 2 posters
- GRED (Clermont Ferrand), invited by V. Mirouse
- Laboratoire de Biologie du Développement (Paris), invited by M. Gho
2012 - The Notch meeting (Athens), Invited speaker
- 1st joint meeting SBCF-SFBD ‘When Development meets Cell Biology’, (Montpellier) invited
speaker
- Institut Jacques Monod (Paris) Invited by A. Guichet
- Annual Drosophila Research Conference (Chicago), Talk (selection on abstract)
- IBDML (Marseille) invited by L. Kodjabachian
- ESF- EMBO Conference on Cell Polarity and Traffic Membrane, Pulstuk, Poland, Talk (selection on
abstract)
2011 - Annual Drosophila Research Conference, San Diego, USA, March 30-April 3, poster
- EMBO Worshop on Septins, St Goar (Germany, March 6-9), Talk (selection on abstract)
9- Scientific animation
2015- organizing committee- The Notch Meeting, Athens (Greece)
2011 - Cell Cycle, Cancer and Development Meeting, St Malo, local organizing committee
2008 – organization of the ‘XIième rencontres Exocytose-Endocytose’- Batz sur Mer,
2007 - co-organization of the 'premières journées Interface Chimie-Physique-Biologie' de Rennes
10- Funding
2014-2019- Equipe Labéllisée Ligue Nationale contre le Cancer
2014-2016- FRM- Projet Innovant (genome editing and optognetics)
2014-16- Merlion Project- collaborative project with Dr Y. Toyama, NUS-MBI, Singapore
2012-2015 ANR blanc SVSE2-ApiNotch (Porteur)
2012-2015 ANR blanc SVSE5- KinBioFRET (Partners: M. Tramier & C. Prigent)
2011-12 La Ligue contre le cancer comité 35
2009-2012 ANR PNANO- Nanoparticles as modulators of signaling pathways (Partners: Z.
Gueroui, V. Marchi-Artzner, C. Gosse)
2009-2011 INCA: Exosome biogenesis and use in immunotherapy against tumors (partners: M.
Labouesse, G. Raposo)
2008-2010 Association pour la Recherche sur le Cancer (ARC-subvention fixe)
2006 Aide à l’installation d’équipes-Rennes Métropole- Equipment
2006 FRM aide à l’installation d’équipes-Equipment
2006-2010 ACOMB (Accueil de Compétences en Bretagne): Investigating the role of membrane
trafficking during Notch signaling in Drosophila
2006-2011 ATIP+ CNRS double label ‘Biologie du Développement’ et ‘Biologie cellulaire’
11- Evaluation of the team by AERES and the SAB
SAB evaluation 2010
Dr. Leborgne is a thoughtful scientist who is well respected in the area of asymmetric cell division
and Notch signalling. He has been consolidating his research identity during the past 4 years as a
Team Leader. For example, he has proposed an interesting new model on how trafficking might
regulate the apico-basal distribution of Notch and its ligand and hence their ability to interact. He
has also two stories in the pipeline, including one on the trafficking of Sanpodo. We expect these
papers to be published this year and that they will confirm Dr. Leborgne’s position as a Team
Leader. It is important that no effort is spared to ensure that these papers come out in good
journals. During the past 4 years, Dr. Leborgne has also developed long term projects that have the
right balance between risk and originality. Overall, once Dr. Leborgne has 2-3 papers under his belt
as a group leader, he will be well under way to put his group on the map.
Score: A+
AERES-evaluation 2010 (conclusions only, full report can be find at
(http://www.google.fr/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCIQFjAA&url=http%3A%2F%2Fwww.aeresevaluation.fr%2Fcontent%2Fdownload%2F16693%2F264488%2Ffile%2FB2012-EV-0350936C-S2UR120001333-RD.pdf&ei=BzMBVYnoKIp7AbnvIC4Ag&usg=AFQjCNETulSM1hextXQKqT3VVJZwoPfoEg&sig2=AhCV95CCX1gtxAXnOowy3A&bvm=bv.87920726,d.ZGU)
A young, dynamic team exploiting a powerful genetic system to ask fundamental questions
about membrane traffic and its role in cell fate decisions.
Strengths and opportunities
The leader has proven an excellent scientific leadership. He has a clear vision on how to run his
research program, asks original questions and applies innovative approaches.
The project is exciting and ambitious. Feasible if the group can grow. The leader was able to
establish a very good international network and to be in contact with the possible main competitors
in his field.
Weaknesses and threats
The group might be too small to address all the questions raised and become really competitive
with the strongest players in the Developmental Cell Biology field.
Recommendations
The recommendation of the committee is to continue in this excellent direction. As all the
prerequisites are there (successful team, very good scientific environment, excellent facilities), the
leader should be more active in attracting international postdocs.
SAB evaluation2015:
The Le Borgne group has very robustly established itself in the institute. This is reflected in an
excellent list of publications that have had a very important impact in the fields of asymmetric
division, Notch signaling, membrane trafficking and epithelial biology. The work is original and solid,
and Dr Leborgne’s is recognized in these fields.
He is now making a very timely move into the mechanics of the epithelia, a very exciting field at
the moment. He approaches this by means of quantitative strategies that will give important
insights into epithelial mechanics, but also (in a very original approach) into the mutual interplay
between signaling and physics. Quantitative imaging and theoretical physics will be important
requisites for this approach. In order to establish this strategy, a tenured position for the postdoc
that initiated this approach in his lab will be essential.
12- Research activities and Main Facts
Previous major scientific achievements
Asymmetric cell division (ACD) is a conserved mechanism by which cell fate diversity is generated during
development and throughout adult life. How a cell can produce two daughter cells with different identities
and how defects in this asymmetry contribute to diseases are the fundamental questions we study using the
Drosophila adult sensory organ (SO) lineage as a model system. SO Precursors (SOP) are epithelial cells
present in a single layer neuroepithelium on the dorsal thorax of Drosophila. SOP undergoes a series of four
ACD in which a mother cell gives rise to two daughter cells via uneven segregation of the Notch regulators
Numb and Neuralized. Thus, at each division, the acquisition of cell identity is controlled by the differential
activation of Notch. Notch is activated by Delta (Dl) present on the surface of adjacent cells. Our recent work
contributed to show that sorting of N and Dl along the apico-basal axis at the exit of mitosis is important for
proper N activation. We identified new regulators of N signaling following asymmetric cell division including
membrane traffic regulators (AP-1) and regulators of epithelial cell cytokinesis (septins). We investigate the
molecular mechanisms by which AP-1 and septins controls N signaling by studying: - novel AP-1 interacting
factors and traffic regulators identified by genetic and biochemical means, - the role of AP- 1 on the transport
of E-Cadherin (E-Cad), - the role of AP-1 and E-Cad in the organization of N signaling platform, - the
remodeling of the junctions and the maintenance of epithelial cell polarity throughout ACD.
1- Spatio-temporal regulation of Notch activation by membrane trafficking
Using a compartmentalized antibody uptake assay, we propose that Neuralized-dependent transcytosis
regulates the signaling activity of Delta by relocalizing Delta from a membrane domain where it cannot
interact with Notch to another membrane domain where it can bind and activate Notch (Benhra et al, 2010).
To elucidate the intracellular routes followed by Notch and ligands during binary cell fate acquisition, we next
performed a RNAi screen and identified 20 new regulators including the AP-1 adaptor complex and the
septins (Le Bras et al, 2012). Using a combination of in vitro, ex vivo and in vivo approaches, we also
observed that Delta can be sorted into exosome-like vesicles and could regulate long distance Notch
signaling in vitro. Whether ELV have a functional significance in vivo remains unsolved (Monier et al,
unpublished observations). Similar observations were made for the morphogen Wingless in collaboration
with the team of J-P Vincent, NIMR, London (Beckett et al, 2013).
2- Role of AP-1 in Notch signaling and cell-cell adhesion
We identified AP-1 complex as a negative regulator of Notch signaling. It does so by regulating the
endocytic recycling of Notch and its cofactor Sanpodo towards newly formed E-Cadherin adhesive contacts
at the SOP daughter cell interface (Benhra et al, 2011). We further show that AP-1 acts through Numb and
demonstrate that Numb inhibits Sanpodo recycling rather than endocytosis as previously thought (Cotton et
al, 2013). This activity is tightly controlled by cell cycle. Together with the group of C. Prigent (IGDR,
Rennes), we found that the mitotic kinase Aurora A phosphorylates Numb and controls it ability to interact
with the AP-1 complex (Cotton et al, in revision). On a side project, in collaboration with J. Brill (U. Toronto),
we found that another evolutionarily conserved function of AP-1 is to control secretory granule biogenesis
(Burgess et al, 2011).
In addition, we found that AP-1 regulates E-Cad trafficking in epithelial cells (collaboration with U. Tepass,
Toronto) and in female germline cysts where sustained E-Cad dependent adhesion organizes a microvilli
meshwork and ensures proper attachment of ring canals (resulting from incomplete cytokinesis) to plasma
membrane (Loyer et al, submitted beginning of 2015).
3- Epithelial cell cytokinesis and cell mechanics
How adhesive contacts with neighbors affect epithelial cell cytokinesis was unknown. We reported that,
septins (identified in our screen (Le Bras et al, 2012)) are specifically required for planar (but not orthogonal)
cytokinesis. During planar division, cytokinetic furrowing initiates basally, resulting in a contractile ring
displaced toward the adherens junction (AJ). The formation of new AJ between daughter cells requires the
disengagement of E-Cadherin complexes between mitotic and neighboring cells at the cleavage furrow,
followed by the assembly of E-Cadherin complexes on the daughter-daughter interface. The strength of
adhesion with neighbors directly impacts both the kinetics of AJ disengagement and the length of the new
AJ. Loss of septins causes a reduction in the contractility of the actomyosin ring and prevents local
disengagement of AJ in the cleavage furrow. By modulating the strength of tension induced by neighbors,
we uncovered a mechanical function for septins to overcome the extrinsic tension induced by neighboring
interphasic cells (Founounou et al, 2013; Le Bras and Le Borgne, 2014). This pioneer work opened new
avenue of research on epithelial cell mechanics and Notch signaling (see projects).
4- Biophysical approaches
Upon arrival in Rennes, I decided to team up with physicists (Z. Gueroui) and chemists (V. Marchi-Artzner)
in order to develop novel methodological approaches for spatio- temporal control of signaling activities (Dif
et al, 2009). Decisions on the fate of cells and their functions are dictated by the spatiotemporal dynamics of
molecular signaling networks. However, techniques to examine the dynamics of these intracellular
processes remain limited. As a proof of concept, we have shown that magnetic nanoparticles conjugated
with key regulatory proteins can artificially control, in time and space, the Ran/RCC1 signaling pathway that
regulates the cell cytoskeleton (Hoffmann et al, 2013). This pioneer quest is at the basis of the novel
methodological approaches including optogenetics we are currently developing.
Research plan for the next 5 years
1-Methodological developments-I. Gicquel, Irina K. and P. Uhart
We have begun to implement genome-editing tools based on CRISPR/Cas9 methodology. We are now
generating Knockout, Knock-In, introducing point mutations, and gene tagging in routine. In parallel we
develop optogenetic tools to conduct spatio temporally controlled gene product inactivation. This approach is
based on the ability of Arabidposis thaliana crytpochrome 2 to dimerize with CIBN upon light activation at
seconds time scale and in a reversible manner. The idea is to perform knockside away experiments of
membrane traffic regulators (AP-1, Numb, and novel regulator identified in our screen (Le Bras et al, 2012)
or to force the membrane localization of enzymes such as kinases or phosphatases.
I. Kolotuev develops correlative light and electron microscopy (CLEM) approaches and EM-immunolabeling.
2- cytokinesis and abscission of epidermal cells-E. Daniel and I. Kolotuev
As a direct follow up of our study on septins in epithelial cell cytokinesis (Founounou et al, 2013), we are
focusing on the late steps of cytokinesis, namely abscission and investigate the role of evolutionarily
conserved ESCRT machinery, that of polarity complexes and components of cell-cell junction during
epithelial cell abscission.
3- regulation of SOP cytokinesis and abscission-link to Notch activation- K.Bellec, S. Le Bras
Work from several groups (H. Bellen, M. Gonzalez-Gaitan, F. Schweisguth) including ours has pinpoint that
Notch signaling takes place during cytokinesis. Several non-mutually exclusive models involves distinct
modalities for Notch activation: activation from asymmetrically inherited Sara endosomes (M. GonzalezGaitan), activation at the basal interface separating SOP daughter cells (F. Schweisguth) and/or activation at
the apical interface (H. Bellen and R. Le Borgne). To address when and where the productive
ligand/receptor activation takes place, we will develop novel reagents (genome editing), and further develop
our non invasive and quantitative live imaging approach combined to genetic dissection of the process to
define epithelial cell polarity transmission, polarity of the novel SOP daughter cell interface, kinetics of
formation and composition of the novel adhesive interface that we hypothesize serves as a launching
platform for Notch activation.
In parallel, functional characterization of membrane traffic regulators (Le Bras et al, 2012) will be performed.
4- role of mechanical forces in epithelial cell cytokinesis and fate acquisition- M. Pinot
Cell biophysics approaches including laser nano-ablation, optical tweezers and FRET-based E-Cad tension
sensor are being developed to investigate the role of tensile forces during epithelial cells
cytokinesis/abscission, and within the novel adhesive interface of non-signaling epidermal cells versus that
of SOP daughter cells (launching platform), i.e. investigate mechano-transduction in signal transmission.