Ophiocordyceps unilateralis is a group of insect-infecting fungi known for their ability to manipulate behavior. They do so to help themselves spread easier to new hosts. In this way, they are reminiscent of the pathogens from various zombie movies that infect humans and cause them to behave in ways that spread the disease (e.g. biting). For this reason, these fungi are often referred to as "zombie fungi". Fungi in general are a well known source of many chemicals that can be used for therapeutic purposes. Antibiotics are a common example of fungal chemicals that can be used to keep people healthy. For that reason, our research team is interested in exploring this group of fungi, which is known to affect the nervous system of mammals, in hopes of finding new compounds that can be used to help with behavioral disorders. Understanding how these "zombie-making" fungi are able to affect the nervous system is thus an important step towards exploring if these chemicals have any therapeutic use. The behavioral effects caused by these fungi are well described in nature, particularly in ant-infecting Ophiocordyceps. Previous studies have shown that in zombie ants the fungus first disrupts the social behaviors of its host, reducing their communication with nestmates and causes them to leave the nest, abandoning their social roles. This is important for the fungus because it allows the parasite to avoid detection and potential destruction by nestmates. These zombie ants then exhibit a climbing behavior known as summit disease, where they climbing nearby vegetation to a higher point that aids in the fungus's growth and spore dispersal. Finally, the ant bites down onto the plant material at this elevated position, ensuring that it remains stuck to the plant after death when the fungus grows out of the ant from the back of the head and makes new spores to infect new ants. By causing these behavioral manipulations, the fungus is better able to spread its spores further using the wind. However, while the behaviors may be well known, the chemicals involved in these behavioral manipulations have been more difficult to uncover. This is partly due to the fact that these fungi are hard to work with in a laboratory setting, making many of the modern day genetic tools unavailable to them. For this reason, this project focused on exploring ways that other model organisms, like bacteria, yeast, and nematodes, that are much easier to work with, could be used to help explore the functions of compounds from Ophiocordyceps species, particularly small secreted proteins. Because this project incorporates so many different organisms, it spans many biological sub-disciplines, and thus, lends itself well to the international exchange of personnel, advanced training, and ideas. If we are able to use the molecular genetics tools available to these more easy to work with model organisms, then we can bypass the barriers of working directly with the fungi in lab and open the door for rapid study of new fungal compounds. This approach would not only make studying zombie fungi much easier, but it would also create tools that can be used by a lot of other types of scientists who are interested in exploring the neurobiology of other hard-to-work-with insects, such as those that cause damage to agricultural crops.
