PhD position: Study the cellular infection biology of Salmonella diarrhea with an in vivo-like tissue culture model

The Hardt lab studies Salmonella diarrhea. We are interested in the molecular and cellular mechanisms that explain how the food-​borne pathogen colonizes the gut, infects the gut tissue and causes disease.

Salmonella Typhimurium is a common cause of diarrhea resulting in much morbidity world-wide. As we are lacking vaccines and therapies, we need further research to identify targets for intervention. Research on the pathogen’s virulence factors and the host’s innate immune responses have been performed in mice or simplified tissue culture models. However, due to the lack of realistic tissue culture models, there is an important gap in our understanding of the molecular and cellular processes triggering gut tissue infection, inflammasome activation the extrusion of infected enterocytes.

The Hardt lab offers a fully funded PhD project aiming to establish an in vitro (i.v.) gut epithelium infection model which closely re-capitulates the real infection. The project will use this optimized setup to decipher the function of the Type III secretion system 1, enterocyte manipulation by the translocated effector proteins and the host’s innate immune defence.

Selected literature:

Fattinger, S.A., Böck, D., Di Martino, M.L., Deuring, S., Samperio Ventayol, P., Ek, V., Furter, M., Kreibich, S., Bosia, F., Müller-Hauser, A.A., Nguyen, B.D., Rohde, M., Pilhofer, M.*, Hardt, W.D.* and M.E. Sellin* (2020) Salmonella Typhimurium Discreet-Invasion of the Murine Gut Absorptive Epithelium. PLoS Pathogens 16(5):e1008503. doi: 10.1371/journal.ppat.1008503. free PMID: 32365138.
Hausmann, A.*, Felmy, B., Kunz, L., Kroon, S., Berthold, D.S., Ganz, G., Sandu, I., Nakamura, T., Zangger, N.S., Zhang, Y., Dolowschiak, T., Fattinger, S.A., Furter, M., Müller-Hauser, A.A., Barthel, M., Vlantis, K., Wachsmuth, L., Kisielow, J., Tortola, L., Heide, D., Heikenwalder, M., Oxenius, A., Kopf, M., Schroeder, T., Pasparakis, M., Sellin, M.E. and W.D. Hardt* (2021) Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF. J. Exp. Med. Vol. 218 No. 11 e20210862, https://doi.org/10.1084/jem.20210862. Free PMC PMC8480669.
Fattinger, S.A.*, Sellin, M.E.* and W.D. Hardt* (2021) Salmonella effector driven invasion of the gut epithelium: breaking in and setting the house on fire. Curr. Opin. Microbiol. 64:9-18. doi: 10.1016/j.mib.2021.08.007. Free access.
Fattinger, S.A.*, Maurer, L., Geiser, P., Bernard, E.M., Enzm U., Ganguillet, S., Gül, E., Kroon, S., Demarco, B., Mack, V., Furter, M., Barthel, M., Pelczar, P., Shao, F., Broz, P., Sellin, M.E.* and W.D. Hardt* (2023) Gasdermin D is the only Gasdermin that provides protection against acute Salmonella gut infection in mice. PNAS 120(48):e2315503120. doi: 10.1073/pnas.2315503120.

• An MSc or equivalent in the fields of Biology, Biochemistry or related fields
• Good written and oral communication skills in English (C1 or higher)
• Some knowledge of data analysis and a willingness to familiarize yourself further with relevant scientific software tools
• Experience with two or more of the following: tissue culture, organoids, cell biology, infection biology, FACS, fluorescence microscopy
• Good communication skills
• Ability to work in a team, have problem-solving skills, and the ability to self-organize and take personal responsibility in the fulfilment of tasks
• A curious mind, a positive attitude, a love of research

The PhD student will benefit from the lab’s expertise in Salmonella infection models and our large network of collaborators at ETH Zurich, the NCCR Microbiomes and world-wide partners. The Life Science Zurich graduate School will provide further opportunities for networking and technical support.

Start date: May 1st 2024, or later as negotiated.

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