Doctoral dissertation

Regulation of asymmetries in gene expression might have a significant role in cell functioning

Tohtori
The results presented in this dissertation suggest that asymmetries in gene expression may be crucial for decision-making in bacteria, since they can be regulated by DNA sequence, the levels of regulatory molecules, and temperature shifts. These findings should be of use both for better understanding of natural systems and for fine-tuning behavior of synthetic gene circuits.

Even the simplest of living cells have evolved intricate machinery that allows surviving, reproducing, and performing other functions under various conditions. One of the qualities that allow bacterial cells to survive and thrive in diverse, fluctuating environments is the ability to adjust their properties and behavior depending on the environmental conditions. This ability requires coordinated work of small genetic circuits that provide the cell with the means for decision-making.

The information needed for these genetic circuits to function is encoded in genes, which are stored in the cell in the form of DNA. Two main steps of gene expression are transcription and translation. Transcription is production of an RNA molecule that corresponds to the nucleotide sequence of a particular gene from the segment of DNA that contains this gene. Translation is production of protein molecules from the RNA molecule. The behavior of small genetic circuits depends, among other factors, on the ability of protein numbers to cross certain thresholds for a sufficient amount of time. In bacteria, RNA numbers largely define protein numbers and thus can be used to study the decision-making processes.

Previous studies outlined the effects of mean and variance in RNA or protein numbers on the behavior of small genetic circuits. However, the distribution of RNA or protein numbers is often highly asymmetric, and this is not accounted for when considering only the mean and variance of the distribution.

Sofia Startceva’s dissertation demonstrates that these asymmetries can significantly affect the threshold-crossing abilities of molecular numbers. Further, these asymmetries can be regulated by DNA sequence, levels of regulatory molecules, and temperature shifts. These findings suggest that asymmetries in the distribution of RNA or protein numbers may play a key role in bacterial decision-making. The results obtained in this dissertation could be of use for investigating how regulation in bacterial transcription initiation affects functionality of natural genetic circuits and synthetic genetic constructs. This research might be of relevance especially for medicine and pharmaceutics, and possible future applications of this research may contribute to the betterment of the human society.

The doctoral dissertation of MSc (Tech) Sofia Startceva in the field of biomedical sciences and engineering titled Regulation of Single-Cell Bacterial Gene Expression at the Stage of Transcription Initiation will be publicly examined in the Faculty of Medicine and Health Technology at Tampere University at 13 o’clock on Monday 17.02.2020 in the auditorium F115 of the Arvo building, Arvo Ylpön katu 34, Tampere. The Opponent will be Professor Heinz Köppl, Technische Universität Darmstadt. The Custos will be Professor Andre S. Ribeiro, Faculty of Medicine and Health Technology of Tampere University.

The dissertation is available online at http://urn.fi/URN:ISBN:978-952-03-1440-8