Our laboratory studies the molecular mechanisms of post-transcriptional gene regulation in bacteria, particularly under stress conditions and during bacteriophage infection. We are interested in how RNA-binding proteins and small regulatory RNAs control translation, RNA degradation and bacterial adaptation to changing conditions. 

We combine molecular and systems-level approaches. At the single-molecule level, we use TIRF microscopy to observe the formation of RNA-protein complexes in real time. At the cellular level, we investigate how bacteriophages reprogram host RNA metabolism and translation, and how this knowledge may help identify new antimicrobial strategies. 

We apply this integrated approach to commensal and pathogenic E. coli strains, as well as clinically relevant bacteria such as antibiotic-resistant Acinetobacter baumannii.

Research Summary

Our research programme focuses on the principles of bacterial gene expression regulation. At the molecular level, we use biochemical methods and advanced single-molecule TIRF microscopy to understand how small regulatory RNAs and the Hfq chaperone protein recognize their targets and control the fate of mRNA molecules. 

By monitoring interactions between RNA, proteins, and ribosomes in real time, we study the basic principles of bacterial translational control and RNA degradation. We are interested not only in which molecules interact, but also when these interactions occur, in what order, and with what dynamics successive regulatory steps take place. 

The second major research area concerns bacteriophage infection. We investigate how phages reprogram host RNA metabolism and translation. To do this, we use transcriptomics and proteomics to identify interaction partners and regulatory targets in bacterial cells. 

In 2024-2025, we established experimental systems in antibiotic-resistant Acinetobacter baumannii and E. coli together with their phages. We also identified phage-encoded factors that modulate bacterial translation and RNA regulation. These studies are being developed through active, competitively funded research projects.

Scientific Impact

• Mechanistic insight: our work provides a mechanistic explanation of how small RNAs select their targets and coordinate gene silencing. By analysing the dynamics of target recognition, translation and RNA degradation, we move beyond static models of regulation and describe fundamental principles of gene expression control in bacteria. 
• Advanced technology: we use state-of-the-art single-molecule microscopy to observe regulatory processes in real time. This makes it possible to simultaneously follow RNA targeting, translation and degradation. 
• Potential applications: studies of phage-encoded factors acting on antibiotic-resistant bacteria may open new routes toward antimicrobial strategies against ESKAPE pathogens. Understanding sRNA design rules may also support the development of programmable bacterial regulators for synthetic biology, metabolic engineering and targeted therapeutic interventions. 

Future Goals

In the coming years, we will connect fundamental discovery with therapeutic potential. Our goal is to extend single-molecule analyses to capture the full regulatory path of an mRNA molecule: from its initial recognition by sRNA-Hfq complexes to its final fate at the ribosome. 

We will also use mechanistic insight to study the phage-host arms race in clinically relevant contexts, especially in ESKAPE pathogens.

Collaborations

• We collaborate with Prof. Sander Granneman from the University of Edinburgh to integrate single-molecule visualization with in vivo protein-RNA interaction mapping. 
• We also collaborate with Prof. Ben Luisi from the University of Cambridge to connect regulatory dynamics with mechanisms of RNA degradation. 
• Dr Tom Graefenhan from the Core Unit Systems Medicine in Wuerzburg supports us with transcriptomic analyses of phage infection.

Comment

"Our laboratory studies bacterial gene regulation in two main areas: first, how RNA-binding proteins and small RNAs control translation and couple it to RNA degradation; and second, how bacteriophages reprogram host RNA metabolism and translation. We combine single-molecule TIRF microscopy, which directly visualizes RNA-protein complex formation in real time, with high-throughput transcriptomics and proteomics. This allows us to identify interaction partners and regulatory targets in cells. " says Ewelina Małecka.

Visit the laboratory website for more details: https://maleckalab.com/