Large-scale genomic features and bacterial phenotypes

The project aims to understand how different components of bacterial genomes affect the properties of these organisms, such as the abilities to cause diseases, avoid treatment, and produce chemical components. To date, scientists have been mostly focused on mutations in particular proteins, but this is only the tip of the iceberg. Novel sequencing technologies allow scientists to read the genome deeper and to better understand what is encrypted inside. To use a simple analogy: if we imagine the bacterial genome as a text, scientists have been mostly focusing on the single word level. This project aims to use sophisticated mathematical methods to get insights into the grammar of this text. So, what is hidden in a genome? First, genes matrices that are used to synthesize the proteins. Second, regulatory elements that provide instructions on when and how many proteins should be produced in a cell. These instructions are very flexible, allowing to switch on and off many genes regulating the formation of different proteins in response to environmental conditions. Moreover, numerous repetitive elements in bacterial genomes induce puzzling patterns which might create new capabilities and characteristics for bacteria. Specifically, in bacteria that cause diseases, such repetitive motives in the genome enable randomly alternating ways to create a cell membrane. Subsequently, the human immune system might not recognize these cells as harmful, even if it was trained with these infections before. As a result, such microbes may cause long-term, persistent infections. This project focuses on developing computational methods that will help reveal such mechanisms in important human pathogens and thus help find ways to alleviate them. This will serve as a foundation for developing clinical strategies to treat patients more efficiently and develop better vaccines to prevent further infections. Moreover, many bacteria use similar mechanisms to cause diseases in animals and plants, which eventually may be transmitted to humans. A database with observed genomic features of different bacteria found in different sources will be made publicly available to build upon in further research and industrial applications. From the fundamental science perspective, the project aims to significantly improve our understanding of genome architecture and mechanisms of evolution. This knowledge may enable not only the creation of a better yogurt, but improve many processes that involve bacteria in food production, agriculture, and pharmacology.