Project Details
Projekt
Functional characterization of prenylated Rho proteins in the pathogenesis of Inflammatory bowel diseases
Applicant
Privatdozentin Dr. Imke Atreya, Ph.D.
Subject Area
Gastroenterology
Term
from 2015 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 190140969
Our recent data identified prenylated Rho-A in intestinal epithelial cells (lECs) as a crucial player in gut homeostasis. Accordingly, a spontaneous development of mild intestinal inflammation could be observed in mice lacking Rho-A in lECs. Further supported by decreased expression levels of the prenylation-catalyzing enzyme GGTase-lß and a cytosolic redistribution of Rho-A In lECs of IBD patients, our findings strongly suggest prenylated Rho-A as an important target protein in IBD pathogenesis. In the proposed project we therefore aim at the functional characterization of Rho-A in lEC biology and in the context of chronic gut inflammation. In particular, we will take advantage of genetically engineered mouse strains in order to investigate the impact of lEC-specific Rho-A deficiency on the course of chronic colitis. Analyzing the activation profile and downstream signaling cascades of Rho-A under steady state conditions as well as in the context of mucosal inflammation in murine and human IBD tissue samples will allow us to define its exact role and pathogenic relevance in lEC function. Furthermore, our project will deal with the role of epithelial protein prenylation in IBD. In particular, we will focus on the identification of new prenylated target proteins with potential relevance for IBD, characterized by an altered prenylation status under inflammatory conditions, which would represent interesting candidate proteins for intensified translational investigations.
DFG Programme
Clinical Research Units
