Untangling heterogeneity in DNA replication with nanopore sequencing
About Michael Boemo
Michael Boemo is a postdoctoral research assistant in the Sir William Dunn School of Pathology at University of Oxford with Professor Conrad Nieduszynski, and currently holds the Emanoel Lee Junior Research Fellowship at St. Cross College. Michael completed his PhD in condensed matter physics in 2016 at the University of Oxford where, together with Professor Andrew Turberfield and Professor Luca Cardelli, he developed a computing system comprised of autonomous robots made from DNA. Dr Boemo is interested in developing computational methods to study systems biology, and his current work aims to develop methods to study DNA replication dynamics at single-molecule resolution and a new process algebra for the simulation of biological systems.
Genome replication is a stochastic process whereby each cell exhibits different patterns of origin activation and replication fork movement. Despite this heterogeneity, replication is a remarkably stable process that works quickly and correctly over hundreds of thousands of iterations. Existing methods for measuring replication dynamics largely focus on how a population of cells behave on average, which precludes the detection of low probability errors that may have occurred in individual cells. These errors can have a severe impact on genome integrity, yet existing single-molecule methods, such as DNA combing, are too costly, low-throughput, and low-resolution to effectively detect them. We have created a method called D-NAscent that uses Oxford Nanopore sequencing to create high-throughput genome-wide maps of DNA replication dynamics in single molecules. I will discuss the informatics approach that our software uses, as well as questions pertaining to DNA replication and genome stability that our method is uniquely positioned to answer.