Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Highly Commended in Overall Category 2018

Markéta TomkováWhen choosing my undergraduate university degree, I was deciding between computer science and medicine. Both seemed very exciting and rewarding, but in the end, I chose Computer science at the Charles University in Prague (some say that potentially because it was a larger challenge). I never regretted this a byte and the years of study were both fun and enlightening. Even though pure theoretical computer science is incredibly beautiful and elegant, I was attracted to application of computer science in other fields. When I found that Oxford offered an interdisciplinary DPhil between computer science and biomedical sciences, I was excited to have the opportunity to return to the medical research from a different perspective.

Going through the Life Sciences Interface DTC, I moved to the Ludwig Institute of Cancer Research to study a DPhil under the supervision of Dr. Benjamin Schuster-Böckler and Prof. Skirmantas Kriaucionis. I had initially no idea how fortunate I was with the choice of the project, supervisors, and research groups: not only I could work on an interesting project straight away, in a friendly and inspiring environment, but I could also come up with my own ideas and projects, which we eventually pursued further. Even though a bioinformatician, I would say my primary research interests lie in deciphering biological processes and principles. In this respect, cancer research is very rewarding, as while aiming towards a therapy, one can also gain important insight into how healthy cells work.

My work usually entails obtaining different types of sequencing data from thousands of human genomes, analysing the data using clusters of computers, and forming new hypotheses based on the results and previously published literature. One part of my research interests is studying the role of DNA modifications and damage in mutagenesis. In my first project, I researched the mutational properties of 5-hydroxymethylcytosine, a DNA modification brought into spotlight by Prof. Kriaucionis. We have shown it to be associated with low mutability, posing new interesting question as to whether it might play a role in protection of vital organs such as brain from cancer.

In another project, we explored which of the known mutational processes might be modulated by DNA replication. I developed a novel method to quantify the effect of replication-related features on mutational signatures (characteristic patterns of mutation types). The results suggest that DNA replication or replication-associated DNA repair interacts with most mutagenic processes. Moreover, the analysis gave new insights into mechanisms of mutagenicity in multiple signatures. We are currently working towards the development of lab technology which would allow us to test some of the hypotheses we formed.

Selected publications

Tomkova M, Tomek J, Kriaucionis S, Schuster-Böckler B. Mutational signature distribution varies with DNA replication timing and strand asymmetry. Genome Biology.2018;19(1):129. doi:10.1186/s13059-018-1509-y.

Tomkova M, Schuster-Böckler B. DNA Modifications: Naturally More Error Prone? Trends in Genetics.2018; 34(8):627-638. doi:10.1016/j.tig.2018.04.005.

Tomek J, Tomková M, Zhou X, Bub G, Rodriguez B. Modulation of cardiac alternans by altered sarcoplasmic reticulum calcium release: a simulation study. Frontiers in Physiology.2018; 9:1306. doi:10.3389/fphys.2018.01306.

Tomkova M, McClellan M, Kriaucionis S, Schuster-Böckler B. DNA Replication and associated repair pathways are involved in the mutagenesis of methylated cytosine. DNA Repair. 2017. doi:10.1016/j.dnarep.2017.11.005.

Tomkova M, McClellan M, Kriaucionis S, Schuster-Boeckler B. 5-hydroxymethylcytosine marks regions with reduced mutation frequency in human DNA. Elife. 2016;5(MAY2016):1-23. doi:10.7554/eLife.17082.

Bardella C, Al-Dalahmah O, Krell D, Brazauskas P, Al-Qahtani K, Tomkova M, et al. Expression of Idh1(R132H) in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis. Cancer Cell. 2016;30(4):578-594. doi:10.1016/j.ccell.2016.08.017.