Hardt Lab Research
Research strategy
We study molecular, cellular and evolutionary concepts of bacterial infections. Salmonella Typhimurium, a common cause of food-borne diarrhea, serves as our primary model. The disease results from complex and dynamic interactions between the pathogen's virulence factors and metabolism with the normal microbiota inhabiting the gut, the host's gut epithelium and its immune system. We integrate expertise from biochemistry, microbiology, genetics, cell biology, biomedical imaging, systems biology, mathematical modelling, immunology and evolutionary biology to decipher the basic principles explaining the pathogen's biology, the host's mucosal immune response, and the function of the microbiota during discrete stages of disease.
Funding:
Why Salmonella Typhimurium?
S. Typhimurium (abbreviation for Salmonella enterica subspecies 1 serovar Typhimurium) is an important foodborne pathogen that causes numerous diarrheal infections in Switzerland, Europe and worldwide (external page Mølbak et al., Clin Infect Dis. 2014, external page Kirk et al.,PLoS Med. 2015, see also information from external page CDC and the external page Robert Koch Institute). Read more...
This pathogen offers unique technical advantages for the discovery of novel concepts of general importance in infection biology. Read more...
Finally, there is a wealth of information on the key virulence factors of S. Typhimurium. This provides an excellent basis for mechanistic studies of pathogen-host cell and pathogen-microbiota interactions. We are particularly interested in the type III secretion system 1 (TTSS-1), a syringe-like organelle that allows S. Typhimurium to manipulate and invade into gut epithelial cells (Fig. 1). Read more...
The mouse, a versatile model for studying the steps leading to Salmonella diarrhea.
The S. Typhimurium gut infection is a highly dynamic process. Our early work is summarized in the following reviews (external page Hapfelmeier et al., Trends Microbiol. 2005; external page Stecher and Hardt, Curr Opin Microbiol. 2011; external page Kaiser et al., Immunol Rev. 2012). Each stage of the infection requires distinct sets of S. Typhimurium virulence factors that enable appropriate interactions with the gut microbiota and with diverse cell types of the host's mucosa. For mechanistic analysis we are developing novel in vivo models and combining them with suitable ex vivo assays, biochemical approaches and mathematical modelling.
The stages of the disease that we are currently studying are outlined below (Fig. 2). For detailed information on our ongoing projects, please refer to the project pages.
