How does genome architecture influence cancer risk across animal species?

Sarah McClelland (primary)
Cancer Genomics and Computational Biology
Barts Cancer Institute, Queen Mary University of London
Professor Trevor Graham (secondary)
Cancer Genomics and Computational Biology
Barts Cancer Institute, Queen Mary University of London


Cancer research has recently benefitted from the integration of evolutionary mathematical theory to study somatic genome evolution during tumour development. We have recently shown that in humans, specific chromosome features (such as chromosome size, centromere length and composition) can predispose to instability of specific chromosomes during cell division. Our aim is to understand how chromosome biology across species impacts genome stability, and the likelihood of developing cancer.

Using both experimental and computational biology and analysis of human and animal genomes, this PhD project will investigate mechanistic principles of chromosomal instability during both species and somatic evolution.


1 Worrall JT, Tamura N, Mazzagatti A, Shaikh N, van Lingen T, Bakker B, Spierings DCJ, Vladimirou E, Foijer F, McClelland SE. Non-random Mis-segregation of Human Chromosomes. Cell Rep. 2018 Jun 12;23(11):3366-3380.

2 N. Shaikh, A. Mazzagatti, B. Bakker, D. Muliaditan, D.C.J. Spierings, F. Foijer, S.E. McClelland†. Replication stress generates multiple distinct classes of DNA copy number alteration. BioRXiv

3 Siming Ma1, Akhil Upneja1, Andrzej Galecki2,3,4, Yi-Miau Tsai2,3, Charles F Burant5, Sasha Raskind5, Quanwei Zhang6, Zhengdong D Zhang6, Andrei Seluanov7,
Vera Gorbunova7, Clary B Clish8, Richard A Miller2,3, Vadim N Gladyshev1* Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity eLife 2016;5:e19130. DOI: 10.7554/eLife.19130

4 Cross et al, Sottoriva A*, Graham TA*
Stabilising selection causes grossly altered but stable karyotypes in metastatic colorectal cancer

5 Caulin A, Graham TA, Wang LS, Maley CC, Solutions to Peto’s Paradox Revealed by Mathematical Modelling and Cross-Species Cancer Gene Analysis
Philos Trans R Soc Lond B Biol Sci 2015 19;370(1673):20140222. doi:10.1098/rstb.2014.0222.

Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyGenetics
Techniques & Approaches
BioinformaticsGeneticsMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular Biology