Teaching

Researches

8th Croucher-Pasteur Exchange Programme

The 8th Croucher-Pasteur Exchange Programme will host seminars of two Principal Investigators from Institut Pasteur:

  • Dr Arnaud ECHARD (Membrane Traffic and Cell Division Lab, Institut Pasteur - CNRS, Paris, France)
  • Dr Matthew ALBERT (Department of Immunology, Institut Pasteur, France)
  • Dr Sandrine ETIENNE-MANNEVILLE (Cell Polarity, Migration and Cancer Unit, Insitut Pasteur, France)

Students and post-doctoral fellows wishing to perform research work at Institut Pasteur are also encouraged to search the Pasteur website to identify additional host laboratories of interest. Prospective candidates are invited to contact Anne LI to prepare the Croucher application (please check the Croucher website for eligibility criteria).


"Lipid and F-actin remodeling for successful cell division: Connections to the Lowe syndrome"

Dr Arnaud ECHARD (Membrane Traffic and Cell Division Lab, Institut Pasteur - CNRS, Paris, France)

Date: Tuesday, 17 April 2012

Time: 9:00 a.m. - 11:00 a.m.

Venue: Ms Chen Yang Foo Oi Telemedicine Centre, 2/F, William M W Mong Block, Faculty of Medicine Building 21 Sassoon Road, Pokfulam, Hong Kong

Abstract:
Cytokinesis leads to the physical separation of the daughter cells, and is characterized in animal cells by a complex series of cell shape changes and membrane remodeling. Following furrow ingression, daughter cells are connected for most of cytokinesis by an intercellular bridge, which is cut in a final step termed abscission. Cytoskeleton and lipid composition are profoundly remodeled during late cytokinesis steps, but how this occurs and whether it is important for successful cytokinesis remains to be established.

Growing evidence indicate that membrane traffic has a key contribution in the post-furrowing steps of cytokinesis. In order to identify more precisely the transport routes involved and how they function in cytokinesis, we previously conducted a systematic RNAi screen focused on Rab genes [1]. Rab proteins are key conserved GTPases that control membrane trafficking in eukaryotic cells, by regulating vesicle fusion, targeting and, as we reported recently, vesicle formation [2]. We found that Rab35 regulates an endocytic pathway and is involved in the initial stability of the intercellular bridge, after furrow contraction, by controlling the proper localization of SEPTIN2 in human cells. In addition, we noticed that Rab35 depletion led to additional cytokinesis defects characterized by either delayed or inhibited abscission [1].

I will present the molecular mechanism by which the Rab35 GTPase regulates lipid and cytoskeleton remodeling in terminal cytokinesis steps. We found that Rab35 controls the localization in late intercellular bridges of OCRL, a PI(4,5)P2 phosphatase. Our results indicate that PI(4,5)P2 hydrolysis is a key requirement for local removal of cortical F-actin and therefore normal cytokinesis abscission [3]. I will also discuss how these findings shed new light on the pleiotropic phenotypes associated with a disease, the Oculo-Cerebro-Renal syndrome of Lowe, in which this phosphatase is mutated. Finally, I will present how the Rab35 GTPase itself is regulated by an original ARF/Rab GTPase cascade that we recently discovered [4].

[1] Kouranti et al. Current Biology, 2006
[2] Miserey-Lenkei et al. Nature Cell Biology, 2010
[3] Dambournet et al. Nature Cell Biology, 2011
[4] Chesneau et al., Current Biology, 2012


"Biomarkers Lie: new insights into HCV disease pathogenesis and treatment"

Dr Matthew ALBERT (Department of Immunology, Institut Pasteur, Paris, France)

Date: Thursday, 26 July 2012

Time: 9:00 a.m. - 11:00 a.m.

Venue: Seminar Room 6, LG1/F, Laboratory Block, Faculty of Medicine Building 21 Sassoon Road, Pokfulam, Hong Kong

Abstract:
Treatment for chronic HCV is highly effective, however significant numbers of patients fail to achieve cure. We conducted multi-analyte profiling in order to identify pre-treatment predictors of response to therapy and demonstrated that CXCL10 (or IP-10) as an important negative prognostic biomarker. Given that CXCL10 mediates chemo-attraction of activated lymphocytes, it was counter-intuitive as to why this chemokine correlates with therapeutic non-responsiveness. We offered new insight into this paradox and provide evidence that the plasma CXCL10 in chronic HCV patients exists in an antagonist form, due to in situ NH2-terminal truncation of the protein. We provide evidence that dipeptidylpeptidase IV (DPP4 or CD26), possibly in combination with other proteases, mediate the generation of antagonist form(s) of CXCL10. These data provided the first evidence for CXCL10 antagonism in human disease, and provides a possible contributing factor for why patients fail to clear their HCV.

Based on these observations, we propose new screening tools for managing HCV treatment (and possibly other disease setting); and DPP4 as a novel therapeutic target for enhancing the efficacy of therapy in chronic HCV patients.


"Maintenance and dynamics of adherens junctions during collective migration"

Dr Sandrine ETIENNE-MANNEVILLE (Cell Polarity, Migration and Cancer Unit, Institut Pasteur, Paris, France)

Date: Friday, 12 October 2012

Time: 3:30 p.m.

Venue: Seminar Room 5, LG1/F, Laboratory Block, Faculty of Medicine Building 21 Sassoon Road, Pokfulam, Hong Kong

Abstract:
Collective cell migration is crucial during development as well as in adult organisms where it participates, for instance, in tissue renewal or wound healing. In cancer, cells migrate as groups or chains to invade the surrounding tissue promoting tumor spreading and metastasis. Our aim is to elucidate the molecular mechanisms that control cell migration and to determine how alterations of these mechanisms may lead to the abnormal migration of cancer cells.

Astrocytes are major glial cells of the central nervous system, where they help the neurons to develop, grow and function properly. In response to cerebral disease or lesion, astrocytes migrate in a tightly controlled and collective manner towards inflammatory sites where they participate to the formation of the glial scar. Astrocytes or their precursors give rise to the majority of cerebral tumors, the gliomas. The most malignant forms of these tumors are extremely invasive which renders them difficult to treat. We use primary astrocytes and glioma cells to study the mechanisms of collective migration.

As cells migrate collectively, intercellular junctions maintain the integrity of the cell monolayer while allowing differential movement and rearrangements of adjacent cells. In astrocytes, intercellular contacts are mainly formed by N-cadherin-mediated adherens junctions. Downregulation of N-cadherin is frequently observed in astrocyte derived tumors and lead to the perturbation of cell polarity and to an increased cell velocity. We have analyzed the dynamics of N-cadherin during 2D and 3D collective migration of astrocytes. We show that junctions undergo a continuous retrograde movement associated with the rearward flow of actin fibers. At the cell rear, adherens junctions are disassembled and N-cadherin is endocytosed. To compensate for the continuous rearward flow of adherens junctions, N-cadherin is recycled and transported back to the leading edge before being incorporated into new adherens junctions at the front of adjacent cells. This global turnover of cadherin complexes allows the cells to maintain stable, strong and yet very adaptable cellular contacts and thus favors cooperation between adjacent cells and collective directed movement. Investigating the molecular mechanisms responsible for the dynamics of cadherin complexes at the front, sides and rear of migrating cells, we found that the tumor suppressor p120catenin, which is strongly downregulated in highly invasive gliomas, plays a central role in the regulation of adherens junction dynamics, and thereby control the speed and directionality of collectively migrating cells.

Contact: .(JavaScript must be enabled to view this email address) or Anne Li at +852 2816 8403

Click here to download the poster.