Abstract: Compositions and methods for the treatment or prevention of Gram-negative bacterial strain infection are provided herein. Methods for the manufacture of said compositions are also provided herein.
Type:
Grant
Filed:
March 11, 2011
Date of Patent:
June 14, 2016
Assignees:
GlaxoSmithKline Biologicals, S.A., Utrecht University
Inventors:
Jan Poolman, Michiel Stork, Johannes Petrus Maria Tommassen, Nathalie Isabelle Devos, Vincent Weynants
Abstract: The present invention discloses a Gram negative bacterium in which the expression of a protein involved in LPS transport to the outer membrane is functionally down-regulated such that the level of LPS in the outer membrane is decreased compared to a wild-type Gram negative bacterium. Down regulation of Imp and MsbA proteins can result in such a bacterium. Outer membrane vesicle preparations derived from the Gram negative bacterium of the invention can be used in vaccines to provide protection against bacterial infection.
Type:
Application
Filed:
November 3, 2009
Publication date:
February 25, 2010
Applicants:
GLAXOSMITHKLINE S.A., UTRECHT UNIVERSITY
Inventors:
Martine Petronella Bos, Jan Poolman, Boris Tefsen, Johannes Petrus Maria Tommassen
Abstract: The APC tumor suppressor protein binds to .beta.-catenin, a protein recently shown to interact with Tcf/Lef transcription factors. Here, the gene encoding a Tcf family member that is expressed in colonic epithelium (hTcf-4) a was cloned and characterized. hTcf-4 transactivates transcription only when associated with .beta.-catenin. Nuclei of APC.sup.-/- colon carcinoma cells were found to contain a stable .beta.-catenin-hTCF-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed .beta.-catenin from hTcf4 and abrogated the transcriptional transactivation. Constitutive transcription of TCF target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium. It is also shown here that the products of mutant APC genes found in colorectal tumors are defective in regulating .beta.-catenin/Tcf-4 transcrpitional activation.
Type:
Grant
Filed:
January 7, 1998
Date of Patent:
December 7, 1999
Assignee:
Utrecht University
Inventors:
Nick Barker, Hans Clevers, Vladimar Korinek
Abstract: The APC tumor suppressor protein binds to .beta.-catenin, a protein recently shown to interact with Tcf/Lef transcription factors. Here, the gene encoding a Tcf family member that is expressed in colonic epithelium (hTcf-4) was cloned and characterized. hTcf-4 transactivates transcription only when associated with .beta.-catenin. Nuclei of APC.sup.-/- colon carcinoma cells were found to contain a stable .beta.-catenin-hTCF-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed .beta.-catenin from hTcf4 and abrogated the transcriptional transactivation. Constitutive transcription of TCF target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium. It is also shown here that the products of mutant APC genes found in colorectal tumors are defective in regulating .beta.-catenin/Tcf-4 transcrpitional activation.
Type:
Grant
Filed:
March 20, 1997
Date of Patent:
December 22, 1998
Assignees:
Johns Hopkins University, Utrecht University
Inventors:
Nick Barker, Hans Clevers, Kenneth W. Kinzler, Vladimer Korinek, Patrice J. Morin, Andrew B. Sparks, Bert Vogelstein