Project Reference: TRG27-VET-EM1

Project title: Transposable element regulation in an ancient transmissible cancer

Project outline

Transmissible cancers are unusual diseases of animals which occur when cancer cells themselves become infectious agents and spread through populations. Transmissible cancers arise, like all cancers, by malignant transformation of cells of the body. Unlike “ordinary” cancers, however, which remain confined to that one body, transmissible cancers continue to survive by spreading their cells to new hosts. This requires transmissible cancers to avoid destruction by the new host’s immune system despite their status as foreign “allogeneic” grafts. Once established, transmissible cancers can persist for millennia, spread vast distances, and even cross species barriers. However, very little is understood about genome regulation of these unusual infectious diseases despite their potential to provide unique biological insights of broad relevance.

One of the most fascinating transmissible cancers known in nature is the canine transmissible venereal tumour (CTVT). This is a sexually transmitted cancer of dogs which manifests as genital tumours. Remarkably, CTVT first arose in a single “founder dog” that lived several thousand years ago; it persisted beyond its founder dog by the transfer of cancer cells to new hosts during mating, and subsequently spread throughout dog populations worldwide. Indeed, CTVT is the oldest and most prolific cancer known in nature. CTVT is thus a unique resource with which to understand the long-term genome evolution of somatic cells. 

In this project, which is based at the Transmissible Cancer Group (www.tcg.vet.cam.ac.uk), you will make use of a large panel of CTVT genomes to understand how transposable elements are regulated in CTVT. Our hypothesis is that transposable elements have been massively mobilised in CTVT due to deregulation of genome defence mechanisms and alterations in DNA methylation profiles. We will test this by analysing identities and patterns of transposable elements in CTVT genomes collected from dogs around the world.

Principal Supervisor

Professor Elizabeth Murchison

Email address: epm27@cam.ac.uk

Department / Partner Institute: Veterinary Medicine

Website: https://www.tcg.vet.cam.ac.uk/

BBSRC strategic theme

Understanding the rules of life