News
Christian de Duve's latest book is out
"De Jésus à Jésus en passant par Darwin", published by Odile Jacob.
Click on the link below to see La Libre Belgique's column (October 15, 2011) "de Duve en appelle au message de Jésus":
http://www.lalibre.be/culture/livres/article/692061/de-duve-en-appelle-au-message-de-jesus.html
Hepatic stem cells
Embryonic Ductal Plate Cells Give Rise to Cholangiocytes, Periportal
Hepatocytes, and Adult Liver Progenitor Cells
The main cell types in the liver are the hepatocytes, which exert most metablic functions of the liver, and the cholangiocytes, which line ducts through which bile flows to the intestine. In the embryonic liver, it was considered that a cell population –called ductal plate cells- located around the branches of veins constituted the progenitors of the cholangiocytes, whereas a distinct cell population was considered to give rise to the hepatocytes.
The team of Frederic Lemaigre now used a genetic labeling technique which enables to mark specifically the ductal plate cells in the mouse embryonic liver, and then to follow the fate of the marked cells after birth and in the adult (Carpentier et al. Gastroenterology 2011). It was found that the ductal plate cells give rise to cholangiocytes, as expected, but also to a subpopulation of hepatocytes, thereby revealing that the ductal plate cells have wider differentiation potential than previously thought.
Moreover, the liver has the capacity to regenerate after injury. In some conditions, such regeneration depends on so-called adult hepatic stem cells, the origin of which being debated. The team has shown, using the same genetic labeling technique, that the ductal plate cells give rise to the adult hepatic stem cells, which can now be traced and investigated during liver regeneration.
Orientation-specific signalling by thrombopoietin receptor dimers
(Thrombopoietin Receptor Signals from Different Dimeric Orientations to Promote Physiologic and Pathologic Blood Formation)
Thrombopoietin (Tpo) is a cytokine produced by the liver that is critical for regulation of the formation of platelet cells, the small anucleated blood cells that derive from the cytoplasm of megakaryocytes and that prevent bleeding upon injury. Tpo also regulates the numbers of hematopoietic stem cells and other myeloid cells. The group of Stefan Constantinescu described in 2006 and 2010 mutations around the transmembrane domain of TpoR that induce different levels of receptor activation and myeloproliferative diseases in vivo (Staerk et al., Blood 2006 107(5):1864-71; Pecquet et al., Blood 2010 115(5):1037-48).
The team thought to probe whether this receptor could actually signal from several different individual dimeric conformations. To this end short (28 amino-acid) dimeric peptides were genetically fused upstream of the transmembrane domain of TpoR, in the place of the extracellular domains. A set of seven distinct dimers was obtained, which scanned all possible dimeric interfaces. The laboratory has now shown that only one dimeric orientation of TpoR is totally inactive, while others promote either normal platelet formation, myeloproliferative disorders, and, surprisingly, in one conformation the receptor induces a myelodysplastic disorder resembling another human disease (Staerk et al., EMBO J, 2011, In Press Sep 2. doi: 10.1038/emboj.2011.315.). Thus, subtle differences in cytokine receptor dimerization provide a new level of regulation of function, that is relevant for disease. This property could be exploited by partial agonists, antibodies or small molecules.
Interview with Christian de Duve at the Lindau Nobel Laureate Meeting, 2011
In this Scientific American podcast Steve Mirsky interviews 1974 Nobel laureate of physiology and medicine Christian de Duve about going from a cell biologist to a theorist on evolution and the origin of life (duration 21.25 min).
http://www.scientificamerican.com/podcast/episode.cfm?id=science-legend-christian-de-duve-11-09-09
Guido Bommer obtains a permanent FNRS position
Guido Bommer arrived at the de Duve Institute at the end of 2008 with the support of a Brains-Back-to-Brussels grant from the Region Bruxelles Capitale. He is leading a small research group investigating the role of small regulatory RNAs in different human diseases. Starting from October 2011 he will be supported by a permanent position of the FNRS.
Interferon-lambda protects epithelia against viral infection
Interferons (IFNs) are cytokines that are produced by virus-infected cells. They act on the receptor expressed by neighboring cells to transmit infection alert signals. After stimulation by IFN, cells express a series of genes that make them more resistant to subsequent viral infection.
IFN-lambda was discovered recently and appeared to have very similar activities as the previously known IFN-alpha/beta.
In a previous work, it was found by the team of Thomas Michiels that IFN-lambda acted almost exclusively on epithelial cells, in contrast to IFN-alpha/beta that acts on almost any cell type, suggesting that IFN-lambda evolved as a protection of mucosa against pathogen invasion (Sommereyns et al., PLoS Pathog. 2008 Mar 14;4(3):e1000017....). Now, work performed by the teams of Mathias Hornef (Univ. Hanover) and Peter Stäheli (Univ. Freiburg), in collaboration with our Institute have confirmed the view that IFN-lambda acted as a protection of mucosal surfaces. This work recently published in PNAS showed that IFN-lambda acts in a non-redundant way, to protect the gastro-intestinal epithelium against infection by rotavirus (Pott et al. Proc Natl Acad Sci U S A. 2011,108: 7944-9).
Lauréats Welbio à l'Institut de Duve
Jean-François COLLET
Comprendre les mécanismes rédox impliqués dans le repliement et la réparation des protéines dans l’enveloppe cellulaire: une étape vers le développement de nouveaux antibiotiques
Pierre COULIE
Exploration et analyse d’interactions inefficaces entre des cellules cancéreuses et des lymphocytes T humains
Benoît VAN den EYNDE
Etude des mécanismes d’apprêtement des antigènes et caractérisation de nouveaux sous-types de protéasome
Pierre van der BRUGGEN
Le rôle des galectines dans la régulation de la
réponse immunitaire
Emile VAN SCHAFTINGEN
La réparation de métabolites fautifs, une nouvelle vue de la spécificité enzymatique
Miikka VIKKULA
Identification de nouveaux gènes lymph/angio-géniques en utilisant le séquençage à haut débit.
