Research

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 sources and mechanisms of spontaneous mutations. We use small but mighty bacteria to define the basic mutational processes and explore their role in genome organization, evolution of antibiotic resistance and cancer.

In particular, we aim to understand how collisions between replication and transcription generate mutations. Replication and transcription are the two fundamental processes that use the same DNA template often simultaneously especially in rapidly dividing bacterial cells resulting in collisions between the two machinery. Two major mutation signatures were identified as resulting from collisions: Indels (insertions/deletions) and promoter base substitutions. We are investigating the mechanisms of the mutations generated by replication-transcription collisions.

We are further interested in understanding how genome organization is influenced by the conflicts between DNA replication and transcription. In many bacterial genomes, genes are preferentially encoded on the leading strand of replication so that their transcription is co-oriented with replication, called gene-strand bias. We are analyzing various genomic features that influence and are impacted by the gene-strand bias.

We are also investigating the role of replication-transcription conflicts in the development of antibiotic resistance in bacteria.

We employ bacterial genetics, molecular biology, experimental evolution combined with Sanger & next-generation sequencing and bioinformatics to address the questions.