Ludwig DPhil Studentship - Single Molecule-based Detection of Mutations in Non-clonal cells
A DPhil project available with Benjamin Schuster-Böckler and Skirmantas Kriaucionis, Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford
Mutations in DNA challenge the integrity of heritable information in cells. High mutational load can cause cell death or lead to the manifestation of altered traits which in most cases are detrimental for an organism. One such example is cancer, a disease with one of the highest mortality rates in the developed world. Understanding the pathways that affect mutational load is therefore important both to prevent cancer as well as to treat it. One of the challenges in understanding mutational processes is detecting “non-clonal“ mutations that happen in individual cells before the onset of cancer. This project will aim to employ and refine techniques which enable the accurate identification of rare mutational events in individual cells. We aim to apply these methods to understand the causes of mutational patterns and thereby reveal new potential environmental carcinogens.
The student will be trained in state-of-the-art methodologies to employ massively parallel sequencing to detect mutations, in culturing of bacterial and mammalian cells, molecular cloning, and in the interpretation of complex data.
- Mutational signature distribution varies with DNA replication timing and strand asymmetry. Tomkova M, Tomek J, Kriaucionis S, Schuster-Böckler B. Genome Biol. 2018 Sep 10;19(1):129. doi: 10.1186/s13059-018-1509-y.
- DNA Replication and associated repair pathways are involved in the mutagenesis of methylated cytosine. Tomkova M, McClellan M, Kriaucionis S, Schuster-Böckler B. DNA Repair (Amst). 2018 Feb;62:1-7. doi: 10.1016/j.dnarep.2017.11.005. Epub 2017 Nov 24.
- 5-hydroxymethylcytosine marks regions with reduced mutation frequency in human DNA. Tomkova M, McClellan M, Kriaucionis S, Schuster-Boeckler B. Elife. 2016 May 16;5:e17082. doi: 10.7554/eLife.17082.