RNA MEDIATED REGULATION IN BACTERIA-PHAGE INTERACTION

Phages are viruses that specifically infect and kill bacteria. Phages are ubiquitous because they are the most abundant entities in the biosphere and are found in all habitats where bacteria proliferate. The ways by which phages takeover the bacterial cell for making phage progeny have long served as rich sources of information, inspiration, and tools for modern biotechnology, biology, and medicine. This includes, for example, our ability to make drought and disease-resistant crops or vaccines against infectious diseases like COVID. Inside the bacterial cell, proteins carry out all biological functions. The information for making proteins is carried on a molecule called RNA. Therefore, all biological functions in bacteria depend on how RNA is managed and bacteria use sophisticated processes to manage cellular RNA. To what extent phages depend on or change bacterial RNA management processes to benefit production of phage progeny is not known. In this project, we will study the details of how and why phages depend on and/or change bacterial RNA management processes. Results will advance fundamental knowledge by providing new biological insights into the interaction between phages and bacteria and, looking ahead, could provide new resources and knowledge for beneficial applications in biology, biotechnology, and medicine.

Central to gene expression in all biological systems is the post-transcriptional regulation of RNA. In bacteria, small non-coding RNAs (sRNAs) play a pivotal role in the post-transcriptional regulation of messenger RNA (mRNA). sRNAs can determine whether the targeted mRNAs are destined for translation, translational repression, or degradation. In many bacteria, a core component of post-transcriptional regulation is a protein called Hfq, which facilitates the interaction between sRNAs and their cognate RNA targets. Phages, viruses that infect bacteria, are the most abundant biological entities on Earth. They play important roles in the evolution and ecology of bacterial communities by transferring genes that contribute to bacterial virulence, stress recalcitrance and antibiotic resistance. However, we don't know to what extent phages rely on and/or modulate Hfq-licenced post-transcriptional regulatory networks in bacteria. An emerging concept in bacterial cell biology is that bacteria compartmentalise some aspects of Hfq-licenced post-transcriptional regulatory process and do so by forming subcellular structures, called Hfq-foci, that are analogous to eukaryotic organelles. However, we don't know whether phages (mis)appropriate the Hfq-foci to satisfy their post-transcriptional regulatory requirements.

In this project, we will leverage our experience of the prototypical E. coli-T7 interaction model to provide a holistic understanding of Hfq-licenced post-transcriptional regulatory basis of bacteria-phage interaction. In particular, the following questions will be addressed in this project:

1. Which Hfq-licenced post-transcriptional regulatory networks in E. coli are required for optimal T7 phage development?
2. How do Hfq-licenced post-transcriptional regulatory networks in E. coli change during T7 phage development?
3. Does T7 phage (mis)appropriate the Hfq-foci for its post-transcriptional regulatory needs?