Bacterial gene regulatory network (GRN) is the molecular machine that most enhances bacterial survivability during several stresses, through tailored transcriptional programs involving hundreds of genes. Currently, we lack a deep understanding of the global mechanisms GRNs employ to selectively activate large, specific gene cohorts, within specific time frames, while leaving other genes mostly unaffected.
To answer this, Suchintak Dash used experimental approaches and computational methods to study the mechanisms triggering global transcriptional programs of the bacterium E. coli.
Suchintak used RNA-seq and flow-cytometry, supported by existing large-scale strain libraries to establish that changes in DNA compaction levels are a major trigger of many cold shock responsive genes. Next, through a comparative analysis of the stress response dynamics of neighbouring genes within operons, he found that simple structural features, such as the internal promoters, highly influence the operon’s stress response dynamics in surprising ways, such as RNA polymerase (RNAP) premature terminations. Finally, he developed a synthetic library for measuring the temporal changes in the RNA levels of the native global regulators that will be useful in many future studies.
“Overall, these findings will support future studies on the global regulation in E. coli, which plays key roles in phenotypic adaptation to stresses. Understanding these global mechanisms is critical for grasping how bacteria adapt to environmental challenges – a knowledge that could eventually lead to new approaches in combating bacterial infections”, Suchintak states.
Suchintak Dash is originally from India. In 2019, he joined Tampere University as a doctoral student at the Laboratory of Biosystem Dynamics of Professor Andre S. Ribeiro, after completing his master’s thesis at national University of Singapore. Upon completing his doctoral degree, Dash will continue his research work as a postdoctoral fellow at The University of Oxford.
Public defence on Friday 20 September
The doctoral dissertation of MTech Suchintak Dash in the field of Single-Cell Systems Biology titled Global regulation mechanics of E. coli stress response will be publicly examined at the Faculty of Medicine and Health Technology at Tampere University at 12 o’clock on Friday 20.9.2024. The venue is Kauppi campus, Arvo building, auditorium A109 (Arvo Ylpön katu 34, Tampere). The Opponent will be Dr Christoph Engl from the Queen Mary University of London. The Custos will be Professor Andre S. Ribeiro from the Faculty of Medicine and Health Technology, Tampere University.