The demand for research on ways to mitigate antibiotic resistance has grown over the years. This includes efforts to engineer new categories of antibiotics and drug therapies that employ sophisticated strategies to target bacterial GRNs.
Despite the recent developments in molecular biology and bioinformatics, it is still challenging to establish relationships between the structure and dynamics of the GRNs of E. coli. In E. coli, GRN dynamics are affected by a multitude of variables, making it important to understand how the multi-dimensional nature of GRNs affects its responses to stresses such as environmental changes and antibiotics.
The importance of understanding the regulatory mechanisms of bacterial GRNs is particularly highlighted in studies on antibiotic resistance because existing antibiotics operate through straightforward mechanisms. However, if antibiotics were to simultaneously disrupt multiple elements and/or processes of GRNs, it would hamper the microbes’ ability to acquire resistance.
In her doctoral dissertation, Bilena Almeida applies techniques from computational biology, bioinformatics, and signal and image processing to study the key features of TFN that contribute to the transcriptional regulatory mechanisms which allow the E. coli bacterium to produce vital, temporally ordered responses to genome-wide stresses, such as medium dilution and a shift in temperature.
Almeida’s doctoral dissertation comprises three studies. In them she developed a new protocol and pipelines with variables that were found to be relevant for explaining the structure and dynamics of the gene cohorts that are responsive to medium dilution and cold shock.
“I began by investigating ways to change RNA Polymerase (RNAP) concentrations in live cells without altering the cell’s morphology and composition. RNAP is a global regulator of gene expression whose concentration differs with medium composition,” Almeida explains.
“I then proceeded to study the effects of these RNAP changes in gene expression at the genome-wide level and how the local and global topological features of TFN affect the genes’ response to medium changes. Afterwards, I contributed to a genome-wide study of the GRN response to cold shocks and the antibiotic Novobiocin,” she adds.
Almeida’s research results contribute to understanding how GRNs respond to, and, more importantly, how bacteria adapt to and survive genome-wide stresses that constantly occur in the oral-fecal route. This protocol and the pipelines have the potential to be extended to other bacteria.
“All in all, understanding how E. coli’s TFN determines the genome-wide responses to large-scale stresses could have extensive implications, including gaining insights into cellular and system-wide responses to environmental changes. This marks advances in understanding how bacteria respond to and/or resist antibiotics and drug treatments as well as exploring novel clinical applications related to, among other things, the gut microbiota,” Almeida concludes.
Bilena Almeida was born in S. Nicolau Island, Cape Verde. In 2017, she graduated with a master’s degree in biomedical engineering from the NOVA School of Science and Technology, NOVA University of Lisbon, Portugal. In 2018, she joined the Laboratory of Biosystem Dynamics led by Professor Andre S. Ribeiro to begin her doctoral studies. She is looking forward to continuing her academic career and pursuing a postdoctoral fellowship.
Public defence on Friday 19 January
The doctoral dissertation of M.Sc. Bilena Lima de Brito Almeida in the field of experimental and computational biosciences titled Transcription Factor Network Regulates E. coli’s Genome-wide Stress-response will be publicly examined at the Faculty of Medicine and Health Technology of Tampere University at 12 o’clock on Friday, 19 January 2024. The venue is lecture hall F025 in the Arvo building, address Arvo Ylpön katu 34, Tampere, Finland. The Opponent will be Professor Richard Röttger from the University of Southern Denmark, Denmark while Professor Andre S. Ribeiro from Tampere University will act as the Custos.
The doctoral dissertation is available online.
The public defence can be followed via a remote connection.
Photo: Suchintak Dash