Abstract

“Co-supervisors: Dr Liz Murchison (epm27@cam.ac.uk) and Máire Lawlor (ml28@sanger.ac.uk), https://www.tcg.vet.cam.ac.uk/

The canine transmissible venereal tumour (CTVT) is a transmissible cancer that affects dogs. This disease, which manifests as genital tumours, is transmitted between animals by the transfer of living cancer cells, usually during mating. CTVT originally arose as a cancer in a single individual dog that lived several thousand years ago. Rather than dying together with this original host, CTVT survived by transmitting its cells to other hosts as a foreign graft. Today, CTVT affects dogs around the world, and is the oldest and most prolific cancer known in nature.

CTVT persists at low clinical prevalence (~1 – 5%) in dog populations in most countries. However, the transmission dynamics that underlie this observation are not understood. Limited data on the natural clinical course of disease suggest long-term persistence in affected hosts and occasional immune-mediated tumour regression.

The goal of the project will be to develop and analyse mathematical models representing alternative hypotheses for the transmission dynamics of CTVT within dog populations. Using probability theory and computer simulations, the student will analyse the behaviour of stochastic models to determine conditions that allow the long-term persistence of CTVT at low prevalence. In particular, we will consider the effects of different sources of heterogeneity among dogs (i.e. dog genetic heterogeneity, tumour heterogeneity), and the impact of chemotherapy treatment. The student will have the opportunity to work with epidemiological data and be part of an exciting collaboration between biologists and mathematicians.

Overall, this project promises to broaden our understanding of the interaction between CTVT and its host, both at the individual level and across populations. This has implications for improving our knowledge of the infectious disease dynamics of this common canine pathogen, but also, importantly, may provide frameworks for understanding how CTVT may interact with the host immune system. The mechanisms whereby transmissible cancers interact with their hosts are of broad interest, both in veterinary and human oncology.

Suggested reading 1. Murchison EP, Wedge DC et al 2014 Transmissible dog cancer genome reveals the origin and history of an ancient cell lineage. Science. 343:437-40

2. Strakova A, Ní Leathlobhair M et al, 2016 Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer. eLife. 5, e14552.

3. Restif O, DTS Hayman, JRC Pulliam et al. 2012. Model-guided fieldwork: practical guidelines for multi-disciplinary research on wildlife ecological and epidemiological dynamics. Ecology Letters 15:1083-94. “