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Access Type
WSU Access
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Biological Sciences
First Advisor
Jared M. Schrader
Abstract
NEW INSIGHT INTO THE CONTROL OF THE BACTERIAL TRANSLATION INITIATION MACHINERY
by
AISHWARYA GHOSH April 2025 Advisors: Dr. Jared Schrader Major: Biological Sciences Degree: Doctor of Philosophy In the central dogma of bacteria, translation initiation plays a crucial role in regulating the flow of genetic information into functional proteins. Traditionally, this process has been understood through the Shine-Dalgarno (SD) model, which describes the interaction between mRNA and the ribosome to ensure accurate translation initiation. While the SD model is well-established concept, the mechanisms regulating translation initiation beyond this model, particularly in bacteria like Caulobacter crescentus, which lack SD sites, remain unclear. Furthermore, although it is known that bacteria can survive and adapt to low temperatures, the precise molecular mechanisms behind this adaptation are not fully understood. Environmental factors, such as temperature, can impact the secondary structure of mRNA, but the connection between these factors requires further investigation. Here, I uncover new insights into translation initiation in C. crescentus, revealing that start codon selection is dictated by mRNA secondary structures, with optimal SD spacing further enhancing efficiency when mRNA structures permit ribosomal accessibility. Also, I identify the N-terminal intrinsically disordered region (IDR) of translation initiation factor IF2 as a key player in bacterial adaptation to cold shock. Our findings show that the N-terminal IDR of IF2 promotes phase separation in response to cold shock, enhancing bacterial fitness under low-temperature conditions. Our studies reveal that translation initiation in C. crescentus is regulated by mRNA secondary structures, and the presence of Shine-Dalgarno sequence boost translation initiation efficiency. Additionally, we observe that the formation of IF2 condensates is reversible, suggesting that these condensates are dynamic structures rather than aggregates. Bioinformatics analyses reveal that the N-terminal IDR in bacterial IF2 proteins is conserved across various bacterial species. These condensates could serve as functional analogs of eukaryotic stress granules, which are known to organize cellular stress responses. The insights gained from this work have profound implications not only for our understanding of translation regulation but also for bacterial stress adaptation. Additionally, it discovers a new type of condensate within the bacterial central dogma, contributing to our knowledge of how bacterial cells organize and regulate the biochemical processes. Our findings highlight the potential of bacterial condensates, specifically IF2 condensates, as novel therapeutic targets for the development of antibiotics aimed at combating the worldwide issue of antibiotic resistance in pathogenic bacteria.
Recommended Citation
Ghosh, Aishwarya, "New Insights Into The Control Of The Bacterial Translation Initiation Machinery" (2025). Wayne State University Dissertations. 4236.
https://digitalcommons.wayne.edu/oa_dissertations/4236