Soutenance de Thèse Shiny Martis-Badiaka (CRP)

Titre : Computational Modeling of Virulence genes expression: a study of gene regulation during pathogenesis

Résumé :

Plant pathogens are a major threat to food security all around the world. Virulence genes enable the pathogens to disease the host and pose threats. We study and computationally model the expression of virulence in pathogens. The pel genes, a major virulence factors in pectinolytic bacteria which infect plants and cause soft rot disease. The Pel enzymes released by the pathogen results in the maceration of tissue in crop and facilitate pathogenesis. We model the pel genes in our model organism Dickeya dadantii. We study pelD/E genes which encode proteins with similar enzymatic activities, but also share the same set of transcriptional regulators, thus raising the question of the benefit of this duplication and the specific role of these two genes. We model their expression with respect KdgR repressor and CRP activator. We develop a quantitative dynamic kinetic model of this process, that reproduces the observed behavior of the two genes and explains their specific role in the infection. The regulatory part of the model is based on experimental values, and fitted kinetic parameters are subjected to systematic evaluation. The model is robust and has multiple applications for studying the pathogenesis of pectinolytic bacteria. In addition, we explore the instance of carbon catabolite repression observed during the regulation of virulence genes Dickeya dadantii.
The novel antibiotic seconeolitsin is characterized in the gram-negative model organism Dickeya dadantii. Growth kinetics and MIC studies are carried out.  The variations in the level of supercoiling in the presence of seconeolitsin and novobiocin are quantified and analyzed.  The effect of supercoiling on the expression of genes, especially the pelE gene is studied using the novel antibiotic seconeolitsin. The study explores the role of supercoiling as a gene regulator.

Langue: Anglais

Rapporteurs :

Dr Stephane GENIN, LPMI Toulouse
Dr Hidde de-JONG, INRIA Grenoble

Membres du jury :

Dr Stephane GENIN, LPMI Toulouse
Dr Hidde de-JONG, INRIA Grenoble
Dr Sylvie REVERCHON, INSA Lyon
Dr Sam MEYER, INSA Lyon