Genetics of susceptibility to infectious diseases
An outgrowth of concern about newly emerging and re-emerging diseases and the progressive development of antibiotic-resistant pathogens justifies increased interest in infectious disease research. The clinical outcome of infectious diseases is determined by complex interactions between the pathogen and the genome of affected individuals, under the influence of environmental and stochastic factors. To identify genetic mechanisms of susceptibility to infectious diseases, mouse models are essential. Actually, experimental standardized infection of mice from controlled mating between inbred strains, bred in specific-pathogen-free conditions, with a given dose of pure inoculum offers a powerful approach. This approach eliminates several sources of environmental variance hence making easier the identification of genes influencing host susceptibility. We focus our research on few life-threatening micro-organisms, including Yersinia pestis, the agent of Plague, Salmonella Typhimurium that causes salmonellosis, and the Rift Valley fever virus, responsible for hemorrhagic fever.
Biology of embryonic and adult stem cells
Stem cells are capable of both generating identical progeny, and producing transit amplifying cells (TA-cells) committed to differentiate. Regulation of the number of stem cells, TA-cells and differentiated cells is a crucial problem in multicellular organisms. Defects in stem cell renewal may lead to lineage disappearance or cancer. Many of the features that govern the behavior of stem cells remain unknown. Our research is directed towards understanding what drives stem cell emergence, maintenance, and differentiation of their TA-cells progeny. We are using genetic approaches in the mouse to address these issues in an in vivo context. We focus our research on Notchless, which our lab has discovered as an important regulator of stem cells maintenance. Our aim is to decipher the cellular behaviours and molecular mechanisms underlying Notchless function in stem cells using three main paradigms: embryonic stem cells, the haematopoietic system and the gut epithelium.