Teaching

Researches

7th Croucher-Pasteur Exchange Programme

The 7th Croucher-Pasteur Exchange Programme has hosted seminars of five Principal Investigators from Institut Pasteur:

  • Dr Jean-Christophe OLIVO-MARIN (Department of Cell Biology and Infection)
     
  • Dr Chiara ZURZOLO (Department of Cell Biology and Infection)
     
  • Dr Philippe BASTIN (Department of Parasitology & Mycology)
     
  • Prof Felix REY (Department of Virology)
     
  • Prof Simon WAIN-HOBSON (Department of Virology)

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).

Professor WAIN-HOBSON has funds for either a PhD or a postdoc, regardless of whether candidates can apply to the Croucher Foundation. Don't miss this chance!


"Cells, images and numbers"

Dr Jean-Christophe OLIVO-MARIN, Quantitative Image Analysis Unit, Institut Pasteur, Paris, France

Date: Tuesday, 12 April 2011

Time: 2:00 p.m. - 3:00 p.m.

Venue: Seminar Room 7, LG/F, Laboratory Block, Faculty of Medicine Bldg, 21 Sassoon Road, Pokfulam, Hong Kong

Abstract: The lecture will present specific methods and algorithms for the processing and quantification of 2- and 3-D+t images sequences in biological microscopy. We will demonstrate algorithms of PSF approximations for image deconvolution, image segmentation, multi-particle tracking and active contours models for cell shape and deformation analysis. We will illustrate the application of our methods in projects related to the study of the dynamics of genes in cell nuclei, the movement of parasites in cells and the detection and tracking of microbes in cells. One specific goal in biological imaging is indeed to automate the quantification of dynamics parameters or the characterization of phenotypic and morphological changes occurring as a consequence of cell/cell or pathogens/host cells interactions. The availability of this information and its thorough analysis is indeed of key importance to help deciphering underlying molecular mechanisms of infectious diseases.


"The mechanisms of prion intracellular replication and spreading: role of tunnelling nanotubes"

by Dr Chiara ZURZOLO (Membrane Trafficking and Pathogenesis Unit, Institut Pasteur, Paris, France)

Date: Tuesday, 19 April 2011

Time: 9:00 a.m. - 11:00 a.m.

Venue: Seminar Room 7, LG/F, Laboratory Block, Faculty of Medicine Bldg, 21 Sassoon Road, Pokfulam, Hong Kong

Abstract: Transmissible spongiform encephalopathies (TSE) result from a post-translational alteration in the conformation of a host-encoded GPI-anchored protein called PrPC. Conversion of the normal protein to the scrapie isoform PrPSc is the key event in the pathogenesis of these diseases. In familial forms, the conversion may occur spontaneously as a result of mutations in the PrP gene. Defining the mechanisms of PrPSc generation and the cellular basis for the pathogenic conversion of PrP is necessary to understand the pathogenesis of TSE. The intracellular compartment where PrPC - PrPSc conversion occurs and how this process leads to neurological dysfunction are still unknown. We have analysed the biosynthethic/degradative pathway, exocytic/endocytic trafficking, and the membrane compartmentalization of PrPC and of some mutants responsible for the hereditary diseases. In infected cellular models we are studing the site of pathological conversion and the intercellular spreading. We have recently shown that prion conversion occurs in the recycling compartment (Marijanovic et al., 2009), thus opening the door to novel therapeutical approaches.

Another unresolved question is how prions spread from the periphery of the body (normally the intestine as common site of prion access) to the central nervous system (CNS) and sequentially spread inside the CNS. We were able to show formation of Tunneling nanotubes (TNTs) containing PrPC and PrPSc between cells of the same and different origins including catecholaminergic neuronal cell line (CAD) as well as between dendritic cells (DC) and primary neurons (Gousset et al., 2009). TNTs are thin actin containing membrane tubular connections, detached from the substrate, that form bridges between cells, and may therefore represent an efficient mechanism for the transfer of PrPSc, by the cells at the peripheral entry-site to neurons in vivo. Indeed we demonstrated that TNTs are responsible for the spreading of infectious prions between different cells in colture (Gousset et al., 2009). We have futher shown that immune DCs uptake prions and spread them to neurons via TNTs (Langevin et al., 2010). Based on these data we propose that through the establishment of TNTs, peripheral dendridic cells can spread infection to neurons of the PNS and then by retrograde transport to the CNS. This discovery could have major impacts on prion research and in other fields of cell biology and medicine.


"Assembly of cilia and flagella: a 500-piece jigsaw"

by Dr Philippe BASTIN, Trypanosome Cell Biology Unit, Institut Pasteur, Paris, France

Date: Wednesday, 20 April 2011

Time: 9:00 a.m. - 11:00 a.m.

Venue: Seminar Room 7, LG/F, Laboratory Block, Faculty of Medicine Bldg, 21 Sassoon Road, Pokfulam, Hong Kong

Abstract: Cilia and flagella are eukaryotic organelles composed of 9 doublet microtubules and of a specific set of up to 500 structural, matrix and membrane proteins. They play essential functions in cell motility, movement of surrounding fluids, signal detection and morphogenesis. Alterations of the function of cilia and flagella in humans result in various diseases called ciliopathies. The presentation will discuss the mode of assembly of such complex organelles that implies coordinate expression, trafficking and polymerisation of so many proteins at a given time and a given space. We will focus on intraflagellar transport, a dynamic system necessary for both construction and maintenance of the flagellum.


"Comparative structural studies of viral envelope glycoproteins"

by Dr Félix REY, Structural Virology Unit, Institut Pasteur, Paris, France

Date: Monday, 11 July 2011

Time: 10:30 a.m. - 1:00 p.m.

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

Abstract: I will outline the type of structural studies that we are currently pursuing in my laboratory, which aim at making comparative analyses, using different viruses, to explore the general ways in which enveloped viruses infect new cells, by delivering their genomic material into the cytoplasm. These studies provide insight into the mechanism of induction of the membrane fusion reaction, allow the characterization of the epitopes of recognized by neutralizing antibodies, and highlight potential receptor binding sites on the viral surface. I will show our overall results and describe the strategies that we are using to crystallize the envelope proteins from other viruses that should complement our current picture, and can be very informative to understand these processes in general. In particular, I will focus in a study of a complex of the dengue virus glycoprotein with a neutralizing antibody - termed 5H2 - isolated from a chimpanzee. The dengue virus envelope protein is made of three different domains - DI, DII and DIII. DIII is thought to be responsible for interactions with receptors, whereas DII carries the membrane fusion loop, and DI is located in between the two, at the center of an elongated rod-like molecule. Contrary to most murine antibodies that have been analyzed to date, which target DIII, the antibody repertoire of higher primates appears to contain only few antibodies that bind to DIII. The 5H2 antibody very potently neutralizes dengue virus serotype 4, binding with subnanomolar affinity to DI. This finding highlights the presence of an important epitope in this domain that should be considered for vaccine design in humans. Analysis of the binding mode shows that 5H2 inhibits the fusogenic transition from dimer to trimer – which is paramount to induce membrane fusion. This is in line with studies that show that the 5H2 antibody inhibits at a post-attachment step. Finally, the stoichiometry of binding, together with a Fab decoration pattern on the virion that is very similar to that of the E16 antibody that neutralizes the related West Nile virus, provide important information about the minimum number of free trimers that need to be present at the virion/target membrane contact area in order for infection to occur. Thus, in adition to describing the details of this important epitope, this study provides the first analysis demonstrating the need of several fusogenic trimers available simultaneously to induce membrane fusion by the flaviviruses.


"Novel human restriction enzymes for microbes – part of a much bigger picture"

by Prof Simon WAIN-HOBSON, Molecular Retrovirology Unit, Institut Pasteur, Paris, France

Date: Friday, 7 October 2011

Time: 11:30 a.m. - 1:00 p.m.

Venue: Seminar Room 1, G/F, Laboratory Block, Faculty of Medicine Building 21 Sassoon Road, Pokfulam, Hong Kong

Abstract: Bacteriophage targeted restriction enzymes resulted in DNA cleavage and helped usher in the DNA revolution. A new class of mammalian restriction enzymes, called APOBEC3 polynucleotide cytidine deaminases, have been identified that can edit single stranded retroviral DNA leading to DNA degradation downstream. Both HIV and HBV are vulnerable yet have solved the APOBEC3 problem in different ways. As DNA comes alive when single stranded it is no surprise that DNA viruses such as human herpesviruses being particularly vulnerable. That the APOBEC3 restriction enzymes were viral specific fitted nicely with the observation that several could be induced by type I and II interferons.
Yet given that thermodynamics teaches us that no system is perfect, how does the host cell protect its mitochondrial and nuclear DNA from these enzymes? After all the bacterial genome is protected by a modification enzyme. Here the parallel breaks down. Human mitochondrial and nuclear DNA are edited; indeed some of the APOBEC3 enzymes are pro-apoptotic and appear to be part of an unsuspected DNA catabolic pathway. Every sample of peripheral blood that we have studied, whether they be infectious disease associated or normal controls show signs of APOBEC3 editing of human DNA. There is far more mutation that hitherto expected. It will be argued that cancer is a pathological downside to the evolution of the APOBEC3 locus.

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

Click here to download the poster.