This Faculty Early-Career Development Award (CAREER) supported an integrative research and education project aiming to determine how behavior manipulating parasitic fungi of the genus Ophiocordyceps can hijack the behavior of carpenter ants. Certain parasites manipulate the behavior of their hosts as a means to increase their chances to spread. This is a rather widespread phenomenon that has evolved multiple times, independently across the tree of life. However, our understanding of this phenomenon is very limited. In this project we used the example of the zombie ants ? ants infected and manipulated by a fungus ? as a model to study how behavior changes upon infection, how ant and fungal tissues interact and which fungal and ant genes might play a role in these infection phenotypes. In this endeavor, we used an integrative approach in which we combined infection studies with behavioral assays, micro CT scans, transcriptomics, metabolomics and machine learning to predict protein-protein interactions. Moreover, because this project combined both field and laboratory work, we also collected important data on the natural history of this parasite host interaction that helped us to be able to better interpret our multi-omics data.

While it is generally known that ants infected with Ophiocordyceps climb up the vegetation to bite down at a vantage point that serves the spreading of fungal spores, our results revealed many more details that accompany this classic summit disease phenotype. Our behavioral studies showed that infected ants become arrhythmic and hyperactive while getting lost from foraging trails and failing to effectively communicate with nest mates. Our field studies refined our understanding of summiting by revealing that ants bite down at a very specific light level that might support fungal development. Moreover, these studies led to the discovery of two entirely new fungal species that could potentially be used in the future to battle fungal infections. Taken together, these studies strengthened our hypothesis that light-driven circadian rhythms might play an important role in this parasite-host interactions, which our transcriptomics studies confirmed. In addition to biological rhythms, secreted proteins are very likely to be the means by which Ophiocordyceps interact with and manipulate the ants. Thorough multi-omics investigations that combined independent infection experiments with detailed data analysis through transcriptomics, metabolomics and computationally predicted protein-protein interactions provided us with novel hypotheses about the manipulating proteins secreted by Ophiocordyceps and how they might affect ant host physiology and nervous tissue. To name one interesting outcome among many: we found that a class of proteins that are the major targets of novel drug development, bind to and are affected by fungal proteins. This suggest that some of our work could be used to inform the development of novel drugs in the future.

This project also had an important educational and outreach component. The PI increased awareness about the fungal kingdom and fostered an interest in the sciences with several diverse cohorts of students through a research-intensive course. In addition, through this award a Virtual Reality game about zombie-making was developed together with digital media and game development students. The short game is geared towards young teens, a demographic that often begins to lose their inherent curiosity about science and nature, to explain the life cycle of the fungus in an interactive, immersive and engaging way. Through the game the student encounters subjects surrounding evolution, infectious diseases, fungi and insects. After testing an early version of the game with a broad audience, and improving it based on this feedback, we made the game freely available online for all to download and experience.

Last Modified: 11/01/2023
Modified by: Graham A Worthy