Alisa Rizvanovic defends her PhD thesis

Salmonella is an important zoonotic pathogen for both health and economic reasons globally. This pathogen must adapt to a constantly shifting environment both outside and inside the host, including variations in temperature, acid stress, food shortages, and other factors. For this, Salmonella can adapt its physiology and morphology in response to these changes by altering gene expression to thrive and survive. One of the ways that Salmonella can change gene expression is by using RNA-binding proteins (RBPs), proteins that can, together with small RNAs, regulate the steps that lead to protein synthesis by modulating RNA stability or translation.

Although ProQ has been recently described as a global RPB with the ability to target many RNAs in the cell, we do not fully understand yet what mechanisms it uses and what precise effects has on cell metabolism. Alisa's thesis focused on characterizing the ProQ regulator and its role in controlling protein expression in Salmonella.

Using methods like saturation mutagenesis and high-throughput sequencing, Alisa's work identified the main functional regions in ProQ, showing as well that these regions work via different mechanisms. Her research also determined that ProQ is important for Salmonella motility via modulation of the translation of the flagellar master regulator FlhDC. This role of ProQ in flagellar expression showed also to be important in the induction of persister formation, a type of phenotype in bacteria that allow the cells to survive in higher doses of antibiotics without being resistant.

We congratulate Alisa on her great work and thesis defense and look forward to seeing her next steps.

Want to learn more about Dr. Rizvanovic's work? Check out these links:

• ​Dr. Rizvanovic' published PhD thesis: Adapting to succeed: Post-transcriptional gene regulation in Salmonella
• Saturation mutagenesis charts the functional landscape of Salmonella ProQ and reveals a gene regulatory function of its C-terminal domain. Rizvanovic, A.; Kjellin, J.;  Fredrik Söderbom, F.; and Holmqvist, E. 2021. Nucleic Acid Research.
• RNA-binding activity and regulatory functions of the emerging sRNA-binding protein ProQ. Holmqvist, E.; Berggren, S.; and Rizvanovic, A. 2020. Review on Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms.
• The Small Toxic Salmonella Protein TimP Targets the Cytoplasmic Membrane and Is Repressed by the Small RNA TimR. Andresen, L.; Martínez-Burgo,Y.; Nilsson Zangelin, J.; Rizvanovic, A.; and Holmqvist, E. 2020. mBio.