Genetic interaction landscape of the Escherichia coli transcriptional factor machinery

In Bacteria, transcription factors (TFs) consist of sensory ligand-binding and DNA-binding helix-turn-helix (HTH) domains to respond to the environmental and internal stimuli. Although Escherichia coli is a well-studied model bacterium, yet half of its TFs’ characteristics remain unclear, including 72 genes of unknown function. Using E. coli synthetic genetic array, a quantitative approach to scoring the fitness of single and double mutant genes, I was able to measure pairwise genetic interactions (GIs) among all TFs in rich and minimal media (RM and MM) to create a differential (DF) GI network. DF network analysis demonstrated GIs altered in RM or MM growth conditions. Both static and DF GI networks were also effective in detecting TF pathways, highlighting new roles for uncharacterized TFs (YjdC, YneJ, YdiP) as regulators of cell division, putrescine pathway and efflux pump, and cold shock adaptation, respectively. Pan-bacterial conservation suggests that TF genes with similar GI profiles are co-conserved in bacterial evolution. Moreover, the E. coli TF GI network provided deep insights on conserved genetic association across bacterial phyla that can be valuable to build TF machinery organization, even in pathogens.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Doctoral -- first

Discipline thesis:degree_discipline

Biochemistry

Grantor dc:publisher

Faculty of Graduate Studies and Research, University of Regina

Year dc:date.issued

2022

Author dc:creator

• Hosseinnia, Ali

Advisor dc:contributor.advisor

• Babu, Mohan

Committee members dc:contributor.committeemember

• Raina-Fulton, Renata
• Widdifield, Cory
• Hansmeier, Nicole

Language dc:language.iso

en

DOI

https://doi.org/10.82465/5132

OAI identifier oai:identifier

oai:uregina.scholaris.ca:10294/15524