NEW YORK (GenomeWeb News) – Roche subsidiary 454 Life Sciences is collaborating with researchers at Cold Spring Harbor Laboratory to fight a mysterious disease afflicting one of Australia’s signature animals: the Tasmanian devil.
The CSHL project, led by Tasmanian native Elizabeth Murchison, a post-doctoral researcher, aims to understand the genetics of a fatal cancer ravaging wild Tasmanian devil populations. The team presented its research plan to visiting Tasmanian government officials last week.
“Our efforts to sequence the devil’s genome mark the first time anyone has attempted to use the technology for exploring this particular type of cancer biology,” CSHL Research Director David Spector said in a statement. “When we have a complete view of the devil tumor genes, scientists will be able to identify the cancer-causing genes, which may lead to the development of therapies and vaccines.”
Tasmanian devils are the largest living carnivorous marsupial in the world and are found in the wild only on Australia’s island state Tasmania. The so-called devil facial tumor disease was first discovered in northeast Tasmania in 1996. Since then, the cancer — shown to be an allograft or transmissible cell line — has wiped out nearly 90 percent of the wild devil population in some parts of the state.
The tumor disease gets passed from one devil to another when the animals bite each other or come in close contact. The cancerous cells apparently evade the devil’s immune system and grow aggressively around the animals’ faces until it is impossible for them to eat. Consequently, most infected devils die of starvation. To date, the only comparable allograft-type tumor is the non-fatal, transmissible canine venereal tumor.
Murchison, whose previous research focused on the role of regulatory miRNAs, became interested in spearheading a devil tumor project three years ago, but did not start working on it until last year, when the Tasmanian government sent her a devil tumor tissue sample.
Now, the CSHL group is using several approaches to try to identify the devil tumor’s tissue of origin and to understand how it is controlled by specific oncogenes or tumor suppressor genes. They also hope to use miRNA analysis to compare the tumor with the animal’s normal tissues.
“What’s exciting about this project is anything we find out — because we basically know nothing about this tumor — could potentially be of therapeutic use,” project collaborator Hannah Bender, an Australian National University veterinarian based at CSHL, told GenomeWeb Daily News.
The team is currently sequencing full-length cDNAs from one animal’s tumor and host tissue in an effort to map all the genes expressed in the tumor using 454 Life Sciences’ deep-sequencing technology. They also hope to eventually establish a cDNA library so they can compare gene expression in several tumors, an approach that will help them determine whether the disease is evolving.
In an ongoing collaboration that started several months ago, 454 Life Sciences is contributing personnel and expertise to the studies. CSHL researchers are currently isolating devil tumor RNA and sending it to the company’s lab, where 454 scientists are trying to create a cDNA library. Once they have this library, Murchison explained, it will be possible to start applying microarray technology as well.
“[Microarrays are] something we’re hoping to do once we have the sequence from 454,” Murchison told GenomeWeb Daily News today. “Once we have the sequence we’re hoping to print some arrays.”
Time is of the essence, though, since the devil facial tumors are rapidly spreading across Tasmania. Some predict the disease will move across the state in the next five to 10 years and, at the current rate, wild devils will be extinct in just 25 to 30 years.
Part of the problem, Murchison explains, is that devil populations are “quite horrendously inbred in terms of their genetic diversity.” For example, research published in the Proceedings of the National Academy of Sciences in October suggests this lack of genetic diversity prevents the animals from mounting an immune response.
In that study, Australian researchers investigated whether tumor cells were evading host immune defenses by down-regulating the animal’s major histocompatibility complex, the system that distinguishes between self- and non-self. This was not the case. Instead, their genotype analysis of four microsatellite loci suggests that a lack of MHC genetic diversity makes Tasmanian devils susceptible to the graft-like tumors.
Murchison, Bender, and others have kept in close contact with their Australian counterparts in what may ultimately become an even larger collaboration. “We’re hoping the disease doesn’t wipe out the population in the wild,” Murchison said. “But it looks like it might.”