Scientists investigate RNA binding proteins in bacteria

Cynthia Sharma, a researcher from The Julius Maximilian University of Würzburg (JMU), investigates how bacteria adapts to changing environments, with a specific focus on RNA binding proteins.

How does bacteria adapt to its environment?

When bacteria, such as the foodborne pathogens Campylobacter jejuni or Salmonella, infect humans, they typically contend with a hostile environment. However, due to various mechanisms they can adjust to these conditions and as a result have developed sophisticated survival and adaptation strategies. Sharma focuses on the RNA binding proteins within bacteria such as these, to ascertain their role in response to environmental changes.

Sharma focuses on a specific area of such cellular control that bacteria use to regulate their genes in response to environmental changes. Researchers will explore a class of proteins that can bind RNA molecules and thereby exert major influence on gene expression and cellular processes in bacteria. So far, this class of proteins is largely unexplored.

Sharma has been awarded an ERC Consolidator Grant of €2m to invest in studying this phenomenon, a grant which is awarded to outstanding scientists with a promising career.

During the next five years, Sharma plans to utilise this grant to significantly advance the research into RNA binding proteins. The funds for her project named: ‘Exploring the Expanding Universe of RNA binding Proteins in Bacteria’ (bacRBP), will mainly be employed for the expansion of her team, the purchase of consumables, and the development of new experimental technologies.

Professor Dr Cynthia Sharma. Photo: Petra Thomas / IMIB.

How will this grant be utilised with RNA binding proteins?

The aim of her ERC Consolidator Grant is to identify and characterise RNA binding proteins in bacteria.

“Our project is based on the hypothesis that there is a vast and largely unexplored universe of RNA binding proteins in bacteria that play crucial roles in cellular physiology,” explained Sharma. “RNA-based gene regulation plays a central role in stress response and virulence control of bacterial pathogens.”

For the past two decades, research into this area has primarily focused on small regulatory RNA molecules in the search for the matter involved in RNA-based regulation. Additionally, research into RNA is also a key focus at JMU, where important insights have been gained into the complex regulatory mechanisms involving RNA molecules.

Scientists now intend to investigate further by considering the proteins that can bind to RNA molecules and regulate them. Only a few well-characterised examples are known in bacteria, and they had been identified long ago. They have a so-called ‘RNA binding domain’ with which they can interact with RNA. “This enables them to influence gene expression and, thus, physiological processes of bacteria,” noted Sharma.

What other proteins have been noted to interact with RNA?

Recent research results – including those conducted in Sharma’s lab— have revealed both that there is a minimal number of RNA binding proteins, and there are also proteins that can interact with RNA despite the lack of canonical RNA binding domains.

Among them are metabolic enzymes, or proteins that are important for cell division. The interaction of these proteins with RNA was considered to be unexpected. “They seem to be moonlighting proteins with a second job,” said Sharma. However, it is still unclear if these proteins influence RNA or if rather the RNA influences the protein.

It is still unknown exactly how many of these proteins exist in bacteria, what tasks they perform, and what regulatory mechanisms they are involved in. With the help of the ERC grant, Sharma and her team aim to address and answer these questions over the next five years.

How will the team’s new method help address these unknown elements?

One major challenge is to identify RNA binding proteins in bacteria. Sharma and her team have recently made significant progress in this area. “My lab has developed a fundamentally new method that can greatly facilitate the systematic identification of such proteins in bacteria,” noted Sharma.

Therefore, with the help of this method, Scientists aim to search for RNA binding proteins under different stress and infection-relevant conditions, with a particular focus on proteins lacking a canonical RNA binding domain. This will be combined with techniques from genomics, transcriptomics, and proteomics, as well as approaches from molecular biology, microbial genetics, and high-resolution imaging techniques.

Sharma and her team aim to address three main goals in the bacRBP project:

  • The establishment of a widely applicable method for the systematic identification of RNA binding proteins in diverse organisms;
  • A greatly expanded set of RNA binding proteins in the two model organisms Campylobacterand Salmonella; and
  • New insights into mechanisms of gene regulation and cell division in bacteria.

“With the bacRBP project, we hope to significantly advance our understanding of RNA binding proteins and the way they regulate physiological processes in bacteria,” concluded Sharma.

This could not only reveal fundamental biological principles, but also could contribute to the development of novel biotechnological methodologies or antimicrobial strategies. This is an increasingly important aspect in view of the growing resistance of many bacteria to common antibiotics.

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