The Sharma lab at the University of Würzburg studies how bacterial pathogens adapt to changing environments and control their virulence. In particular, we aim to unravel mechanisms and functions of gene regulation during stress response and virulence control via small RNAs (sRNAs) and associated RNA-binding proteins (RBPs) as well as small proteins. Our main model organisms are the gastric pathogen Helicobacter pylori and the related foodborne pathogen Campylobacter jejuni. These widespread pathogenic Epsilonproteobacteria are intriguing models for bacterial RNA biology, as they lack homologs of the globally acting RBPs Hfq and ProQ and are thus quite distinct to enterobacterial models, such as E. coli and Salmonella, in terms of RNA-mediated regulation (riboregulation).
To study mechanisms and functions of riboregulation and small proteins in bacteria, we have been developing and employing diverse deep sequencing approaches for global transcriptome/translatome analysis and are combining them with microbiology, RNA biology as well as biochemistry, genetics, and molecular biology approaches. We have also been developing new approaches to globally capture and characterize RBPs in bacteria. Using three-dimensional (3D) infection models based on tissue engineering, we are investigating the roles of sRNAs, small proteins, and RBPs in virulence of H. pylori and C. jejuni. We have also been exploring mechanisms and functions of bacterial CRISPR-Cas immune systems, leading to new biotechnological applications. Our main research areas are as follows:
1. RNA-based regulation in bacterial pathogens
2. Identification and characterization of small proteins in bacteria
3. Biology and mechanisms of prokaryotic CRISPR-Cas systems
Publications from our lab can be found here: