Research Briefs, Science & Technology

New evidence of sticky proteins redefines bacterial cell organization

A team of biologists at McGill are changing the way scientists think about the subcellular organization of bacteria. The research group, led by Dr. Stephanie Weber, Assistant Professor of Biology at McGill, examines the spatial organization of living systems using E. coli, a species of bacteria commonly used in laboratory research. In a recent study published in the journal PNAS, the group found that bacteria are far more organized at the subcellular level than scientists traditionally thought.

Bacteria are classified as prokaryotes, meaning that they lack a nucleus and other membrane-bound structures collectively referred to as organelles. Unlike animal, plant, or fungal cells, bacteria do not discretely compartmentalize their cells with organelles.

The lead author of the study, Dr. Anne-Marie Ladouceur, a microscopy specialist at the McGill Advanced BioImaging Facility, found that bacteria may contain primitive organelle-like structures, contrary to what scientists have believed for decades.  

“We still think of [bacteria] as a ‘bag of enzymes,’” Ladouceur said in an interview with The McGill Tribune

Ladouceur believes that this outdated concept of bacteria vastly understates the degree to which these organisms are organized at the molecular level. To better understand how bacterial cells are organized, Weber’s group took a highly technical approach of tracking single molecules. Rather than using historically ubiquitous methods like light microscopy, Weber’s team instead applied techniques for studying a trendy phenomenon in molecular biology known as liquid-liquid phase separation (LLPS). 

LLPS is the emergence of organelle-like structures through “sticky” proteins that aggregate together, rather than being physically contained by a membrane. This phenomenon is similar to the way oil forms distinct droplets in water, rather than mixing evenly throughout. 

In recent years, LLPS has become a well-established mechanism for subcellular compartmentalization in animal models. Still, strong evidence for its presence in bacteria has previously been elusive, a detail that Weber attributes to their very small size.  

“All of the criteria to define phase separation used to require a droplet bigger than [the E. coli] cells,” Weber said in an interview with the Tribune.

In this study, the sticky proteins comprising the bacterial proto-organelles were identified as RNA polymerase (RNAP). RNAP is a key enzyme that functions in the early stages of gene expression, responsible for copying DNA into RNA. The group has identified clusters of RNAP molecules as the first instance of LLPS organized structures in bacteria. Weber noted that this finding provides evidence for an intermediate mobility state between immobile, DNA-bound, and freely diffusing RNAPs.

Interestingly, their data also provides a potential explanation for a previously noted discrepancy between the high number of RNAP molecules and a corresponding, lower-than-expected level of gene expression. The group’s research provides evidence that many of the intermediate state RNAP molecules are not actively transcribing, prompting future studies to account for low levels of gene expression.  

The McGill team also proposed that bacteria may use LLPS in order to quickly and acutely control the location, activity, and accessibility of these RNAP molecules in response to both cellular and environmental cues and in order to rapidly regulate growth.

This study is the first to provide evidence for the ubiquitous nature of LLPS as a mechanism of organizing cells. It is even possible that LLPS played a role in organizing macromolecules in the context of the RNA world hypothesis for the origin of life on earth, Weber and Ladouceur commented. 

“People have found that RNA and small proteins can form these condensates in vitro, and so [LLPS] could be a way to concentrate in the diluted soup of the RNA world,” Weber said.

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