Mechanisms of infection and virulence of Salmonella in the liver
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a foodborne pathogen that induces gastroenteritis in humans and animals. While most of the research investigating Salmonella infection have focused on intestinal and immune cells, the liver is one of the main targets of Salmonella. The liver is mainly composed of epithelial cells, called hepatocytes, with a strong metabolic function. Still, little is known about how Salmonella can infect hepatocytes and whether Salmonella can persist and grow inside these cells.
The aim of this PhD is to define the mechanisms by which Salmonella infects hepatocytes and mediates its intracellular growth. This knowledge is highly relevant to inform future strategies to reduce Salmonella pathogenicity in the liver.
To do this, the PhD student will get extensive training in in vivo techniques including animal handling and infection, as well as isolation of primary liver cells for characterisation in culture. The student will receive training in cellular biology methodologies including analysis of gene regulation by qPCR and protein expression by western blot, ELISA and immunohistochemistry. The student will also learn microbiology techniques and will receive training in complex methodologies including transposon directed insertion-site sequencing (TRADIS) and its analysis using bioinformatics tools.
This extensive training will provide the student a series of valuable transferable skills essential for the progression of their scientific career.
The project will be carried out at the Beraza Lab in collaboration with the Kingsley Lab at Quadram Institute, co-housing research laboratories with clinical facilities combining basic with biomedical research.
References
Edyta E Wojtowicz et al. Low protein diet protects liver function upon Salmonella infection by metabolic reprogramming of macrophages.
Biorxiv 2024. https://doi.org/10.1101/2024.03.01.582753
Isaacs-Ten, A. et al. Metabolic Regulation of Macrophages by SIRT1 Determines Activation During Cholestatic Liver Disease in Mice. Cell Mol Gastroenterol Hepatol 13, 1019-1039 (2022). https://doi.org:10.1016/j.jcmgh.2021.12.010
Isaacs-Ten, A. et al. Intestinal Microbiome-Macrophage Crosstalk Contributes to Cholestatic Liver Disease by Promoting Intestinal Permeability in Mice. Hepatology 72, 2090-2108 (2020). https://doi.org:10.1002/hep.31228
Blokker, B. A. et al. Fine-Tuning of Sirtuin 1 Expression Is Essential to Protect the Liver From Cholestatic Liver Disease. Hepatology 69, 699-716 (2019). https://doi.org:10.1002/hep.30275
Blokker, B. A. et al. Fine-Tuning of Sirtuin 1 Expression Is Essential to Protect the Liver From Cholestatic Liver Disease. Hepatology 69, 699-716 (2019). https://doi.org:10.1002/hep.30275