Call for research applications
Recently the European Research Council opened a series of calls for groups aiming to solve a number of classic, fundamental questions that have perplexed scientists throughout the ages. Interdisciplinary approaches were welcome; no restrictions were placed on the composition of research teams or the methods to be employed.
Below are some representative applications submitted under Topic 12: “Why did the chicken cross the road?”
Cancer remains an enormous threat to human health, with 9.6 million deaths reported world-wide in 2018. Mortality is most often caused by aggressive metastases, which occur when cells migrate from a tumor, traverse the circulatory system and invade other tissues. While the immune system recognizes and eliminates most cells with metastatic potential, some manage to colonize target tissues and eventually disrupt their functions. In an analogous process, chickens may also migrate from their points of origin and traverse the circulatory system. A few escape elimination by automobiles and make it to the other side of the road, where they frequently engage in disruptive behavior. In some of these fowl, tumors have been detected, at levels that should not necessarily be considered non-trivial. This project will exploit the close homology between the causative mechanisms and behavior of chickens and metastatic cancer cells, in hopes of understanding their ability to escape immuno- and vehicular surveillance with the aim of identifying new targets and novel approaches for therapies.
The canonical Wnt signaling pathway influences a number of processes crucial to the development of embryonic organs by targeting complexes which would otherwise degrade cytoplasmic beta-catenin, thus preventing it from localizing to the nucleus and activating target genes. Recently a knock-down of Wnt in chickens was shown to result in embryonic lethality, and as a consequence a total inhibition of road-crossing activity by adult hens and roosters. Our lab has shown that neither canonical nor non-canonical Wnt signaling offers a complete explanation for this association. This suggests that cells possess a hitherto undetected pathway by which Wnt exerts an influence on gene expression programs. Elucidation of this signaling cascade may resolve questions related to the development of embryonic tissues and the disruptions of developmental programs that lead to the rise of cancer stem cells, ornery chickens and other phenotypes.
2004 saw the completion of the first draft of the genome of Gallus gallus – otherwise known as the chicken – providing researchers with the complete DNA sequence of their first bird. They immediately began trying to separate the meat from the bones of an organism that has long been a main course on the menu of models for biomedical research. The chicken has more chromosomes than humans, partially accounting for extra features such as feathers, beaks, and packing its embryos in eggshells. But presently only 18,346 coding genes have been identified, perhaps accounting for noticeable deficits in their cognitive abilities. Our group recently carried out a comprehensive review of genome-wide association studies (GWAS) related to chickens that have appeared in peer-reviewed publications. We identified 712 gene variants significantly associated with mortality in road-crossing chickens compared to a control group of survivors. Interestingly, we also found a correlation between 5-week survival and susceptibility to various pathogens such as avian flu, perhaps because the longer a bird lives, the more likely it is to acquire an infection. These findings have implications in breeding programs, which may have to choose between extending the lifespans of birds and creating pandemics that cost millions of human lives.
Road-crossing behavior has been observed in birds since the appearance of roads, somewhere around the beginning of recorded history. This activity is fraught with danger, as it makes the bird susceptible to death by horses, camels, elephants, automobiles, Roombas, and various other participants in stampedes. Yet the persistence of road crossing implies that it has some value for survival or reproduction. One possibility is that it promotes diversity within populations that would otherwise experience excessive inbreeding – hens living across the road are less likely to belong to a rooster’s brood. Natural selection through roads has caused distinct species of birds to adapt in different ways. Some developed flight; others hop along electrical lines. Chickens continue to cross roads the old-fashioned way; perhaps they have adapted by simply laying more eggs, ensuring that populations will survive despite significant decimations as road kill. In a few species, such as geese, traffic regulations seem to have become integrated into genetically programmed behavior that prompts them to take advantage of crosswalks and traffic lights. A similar phenomenon is observed in frogs and deer, which tend to cross roads at places where warning signs have been mounted, but these examples are most likely cases of convergent evolution rather than reflecting the principle of common descent.
The giant muscle protein titin is an essential component of sarcomeres, piston-like structures that expand and contract to give muscle fibers their elasticity. Without titin, organisms would basically be lumps of protoplasm, unable to cross roads or anything else without the application of some external force. Our lab uses the chicken as a model system to study the 244 domains which make up the titin protein, which partially unfold through the mechanical forces placed on sarcomeres. We are investigating the possibility that mutations cause truncated forms of the molecule that shorten the stride of chickens and thus result in higher mortality when they cross roads.