Mutations constitute the ultimate source of genetic variation, while also being predominantly deleterious and the cause of genetic diseases. Hence, it is critical to understand the rates and mechanisms of spontaneous mutations. We use small but mighty bacteria to define the basic principles of mutations and explore their role in genome organization, evolution, antibiotic resistance and human diseases.
In particular, we are investigating the link between replication-transcription conflicts and genomic stability. Conflicts between DNA replication and transcription are inevitable, as both processes concurrently use the same DNA template, especially in rapidly dividing bacterial and cancer cells resulting in collisions between their machineries. Such collisions impede replication progression, increase genomic instability and cause spontaneous mutations. Our lab will focus on how collisions affect genome duplication and gene expression leading to mutations.
To address these, we combine genetics & molecular biology with experimental evolution & next-gen sequencing. We believe that these studies will allow us to contribute to mutation biology and the evolution of antibiotic resistance, which may accelerate drug discovery.