Resolving Transcription-Replication Conflict

NIEDUSZYNSKI_E22DTP

At the heart of every cell a conflict is taking place, as the machinery of DNA replication and transcription clash. The conflict is over a specific sequence of DNA, which can only be engaged in either transcription or replication at any one time. Resolving conflicts between these two vital processes is essential for life on Earth, ensuring the genome is copied faithfully and avoiding genome instability, while enabling appropriate gene expression. Cells are able to efficiently resolve these replication-transcription conflict. However, we do not yet fully understand the pathways, which presents an exciting opportunity for a PhD student to join our lab. We have recently developed a novel genomic technology that can detect transcription-replication conflicts, which will allow us to discover pathways that the cell uses to protect the genome.

We offer a highly collaborative, multi-disciplinary PhD between the Nieduszynski (DNA replication; technology development) and Haerty (DNA transcription; bioinformatics) groups. The main aim of the project is to determine the mechanisms employed by the cell to resolve the inevitable conflicts between DNA transcription and DNA replication.

The student will work in a rapidly developing field and gain a unique expertise in nanopore single molecule sequencing, technology development and computational biology. The project will be conducted at the Earlham Institute, a BBSRC supported, world leading research centre for bioinformatics and sequencing technology development. The student will have access to training and career development opportunities at EI and at Norwich Research Park as part of the Norwich Biosciences Doctoral Training Partnership.

References

Müller, C. A. et al. Capturing the dynamics of genome replication on individual ultra-long nanopore sequence reads. Nat Methods 16, 429–436 (2019).

Boemo, M. A. DNAscent v2: detecting replication forks in nanopore sequencing data with deep learning. BMC Genomics 22, 430 (2021).

Gómez-González, B. & Aguilera, A. Transcription-mediated replication hindrance: a major driver of genome instability. Gene Dev 33, 1008–1026 (2019).