Title: Tipping the balance from tolerance to anti-cancer immunity in Tasmanian devils
A transmissible cancer first identified in 1996 has been the primary driver for an 85% decline in wild Tasmanian devils. Recently a second type of transmissible tumour was discovered in wild devils and further threatens the long-term persistence of wild Tasmanian devils. These two transmissible tumours offer a unique opportunity to learn how tumours avoid being killed by the immune system, and the knowledge we acquire from studying these transmissible tumours could have help us to understand cancer and transplant rejection in humans and other species. We have recently developed cutting-edge molecular tools (i.e. recombinant cytokines and checkpoint molecules) for studying and manipulating the devil immune system. The goal of this project will be to assess functional responses of tumour cells and immune cells to cytokines and manipulation of checkpoint molecule and cytokine signalling pathways at the RNA and protein levels. Bioinformatics skills are highly desirable, but not essential.
1. Determine most effective methods for stimulating anti-tumour immune responses using
2. Identify novel immune evasion pathways using RNA-seq
In the past few years I have heard several people say that Tasmanian devils, the animal I am studying for my postdoctoral research, have the strongest bite force of any animal. Interestingly, I have also heard many people say that spotted hyenas, the animal I studied during my Ph.D. research, have the strongest bite for of any animal. Clearly something must give. I will give the devil its due by saying that maybe devils have pound-for-pound the strongest bite, but I have no evidence to back this up. In fact, I doubt that anybody has real evidence to back up their claims about animal bite force.
A former PhD student on the MSU Hyena Research Project actually tried to measure the bite force of hyenas, but they would usually just nibble on the bite force tester, and thus the test isn’t valid. It comes down to a problem of motivation. I suspect that the only time a hyena uses its full jaw strength is when it is cracking open large bones to eat the nutritious bone marrow inside. Hyenas have been known to crack open giraffe femurs, and there is no way that a devil could do that. Check back later for my thoughts about why eating bone marrow would be good for the hyena immune system.
My friend James holding giraffe bones. Try sinking your teeth into those bones!
Bone crushing teeth of a spotted hyena!
If I had to guess which animal actually has the strongest bite force, I would guess an elephant. They literally eat trees. I wouldn’t put my hand in an elephant’s mouth. This finally brings us to the actual topic of this post, how to get blood from a hyena. The research I did to earn my Ph.D. was focused on understanding how spotted hyenas do everything wrong when it comes to getting sick (i.e. eating rotten carcasses, live in large social groups, fight…), but somehow rarely get sick and almost never die of disease as far as I can tell. The most common causes of death for wild hyenas are lions, people, and crocodiles. In order to begin understanding the immune system of hyenas, it was necessary to get blood from hyenas.
As if eating wood isn’t hard enough, this wood is covered with thorns. In the words of my friend Sarah Benson-Amram, “So much for you plant defences!”
So how do you get blood from an animal that can bite your hand off? You use an air rifle to shoot the hyena with a plastic dart filled with an anaesthetic. Click this MSUToday: Learning about hyenas link for a short video about darting a hyena and the measurements and samples we get from the hyena after we dart it. Some of you may recognize the shooter, but mostly you will want to pay attention to my Ph.D. supervisor, University Distiguished Professor and National Academy of the Sciences member Kay Holekamp. She has been running the MSU Hyena Research Project since 1988. If you want to know something about hyenas, she is the person to ask. Actually, she is a very good person to ask about many topics in biology and science in general.
Andy with Hendrix. Yes, she was named after Jimmy Hendrix
Hyenas often have very nice, clean teeth. Andy’s thumb can be used to get an idea about how big the canine teeth are.
One thing that people are often very surprised to learn is that hyenas are actually more closely related to cats than dogs. This is so surprising that even my idol David Attenborough got it wrong in his Life of Mammals documentary. I was also sceptical about this little known hyena fact the first time I heard it, but I have actually confirmed hyena-cat-dog relationship in my own research looking at how the hyena immune system detects potential pathogen. I sequenced the DNA for a group of immune receptors called toll-like receptors (TLRs) and found that the DNA for all 10 of the hyena TLRs that I sequenced was more similar to cat DNA than to dog DNA. See table 2 in Characterization of toll-like receptors 1-10 in spotted hyenas for further details. Check back soon to see latest Wild Immunity research on hyenas which will be published in PloS ONE in October, 2015.
Check out a nice video from Smarter Every Day on the Tasmanian devil facial tumor disease. Most of the people in the video, except the host, are my new colleagues at the Menzies Research Institute Tasmania.