Holmqvist lab

Bacteria are constantly challenged by harsh conditions in their ever-changing natural environments. To survive and proliferate, bacterial cells cope with stressful conditions by rapidly re-wire gene expression. To this end, bacteria have acquired complex gene regulatory networks, which at the post-transcriptional level are dominated by RNA-binding proteins and regulatory small RNAs. We study molecular mechanisms and cellular functions of bacterial RNA-binding proteins and their RNA ligands to understand how these regulatory macromolecules contribute to bacterial growth and survival.

Popular science presentation

The aim of my research is to gain a deeper understanding of the molecular processes that enable pathogenic bacteria to successfully infect and reproduce within human host cells. Previous research has shown that bacterial proteins whose function is to bind ribonucleic acids (RNA), so‑called RNA‑binding proteins, are crucial for bacterial infectivity: bacteria lacking certain of these proteins exhibit strongly reduced virulence, but the underlying reasons for this have not been established. Central to understanding the mechanisms by which RNA‑binding proteins regulate bacterial infectivity is identifying which RNA molecules they bind to during the course of infection. I use state‑of‑the‑art, technology‑based methods to gain deeper insight into the mechanisms employed by RNA‑binding proteins, as well as how the activity of these proteins affects bacterial physiology and virulence.

Research projects

The aim of our research is to understand biological functions and regulatory mechanisms of RNA-binding proteins (RBPs) and regulatory RNAs in pathogenic bacteria. This will lead to a better understanding of the regulatory decisions made by bacteria in adverse environments, such as inside the infected host.

RBPs are built of RNA-binding domains that recognize distinct motifs buried in RNA transcripts. The specific interactions between RBPs and their RNA ligands often result in regulation of gene expression, e.g. by activating or inhibiting mRNA translation, or by altering RNA stability. To understand the function of any given RBP, it is key to identify both its RNA ligands and the specific binding motifs. To do this in a comprehensive manner, we use CLIP-seq (crosslinking and immunoprecipitation sequencing) that allows for simultaneous identification of all RNA sequences bound by an RBP at any given moment. This approach can faithfully inform on cellular recognition motifs and RBP specificities, and reveal regulated cellular processes and regulatory mechanisms. We study Salmonella as a model system for bacterial pathogenesis. Salmonella causes typhoid fever and gastroenteritis leading annually to hundreds of thousands of deaths. Within the human host, a number of harsh environments force bacterial pathogens to rapidly change their physiological state by re-wiring gene expression and activate virulence gene expression programs. To fully understand the infection process, it is therefore critical to understand how gene expression is controlled within the pathogen.

Alumni

Sofia Bergman, former PhD student

Kim Boi Le Huyen, former Postdoc

Liis Andresen, former Postdoc

Thomas Stenum, former Postdoc

Yolanda Martinez Burgo, former Postdoc

Alisa Rizvanovic, former PhD student

 

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