Award Abstract # 1558062
Zombie Ants: Towards a Mechanistic Understanding of the Precise Control of Animal Behavior by a Microbial Parasite

NSF Org: IOS
Division Of Integrative Organismal Systems
Recipient: THE PENNSYLVANIA STATE UNIVERSITY
Initial Amendment Date: February 10, 2016
Latest Amendment Date: February 10, 2016
Award Number: 1558062
Award Instrument: Standard Grant
Program Manager: Mamta Rawat
mrawat@nsf.gov
 (703)292-7265
IOS
 Division Of Integrative Organismal Systems
BIO
 Directorate for Biological Sciences
Start Date: February 15, 2016
End Date: January 31, 2019 (Estimated)
Total Intended Award Amount: $547,000.00
Total Awarded Amount to Date: $547,000.00
Funds Obligated to Date: FY 2016 = $547,000.00
History of Investigator:
  • David Hughes (Principal Investigator)
  • Gang Ning (Co-Principal Investigator)
  • Andrew Patterson (Co-Principal Investigator)
  • Philip Smith (Co-Principal Investigator)
Recipient Sponsored Research Office: Pennsylvania State Univ University Park
201 OLD MAIN
UNIVERSITY PARK
PA  US  16802-1503
(814)865-1372
Sponsor Congressional District: 15
Primary Place of Performance: Pennsylvania State Univ University Park
110 Technology Center Bld
University Park
PA  US  16802-7000
Primary Place of Performance
Congressional District:
Unique Entity Identifier (UEI): NPM2J7MSCF61
Parent UEI:
NSF Program(s): Symbiosis Infection & Immunity
Primary Program Source: 01001617DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1074, 1228, 9178, 9179
Program Element Code(s): 765600
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.074

ABSTRACT

One of the most complex examples of symbiosis in nature is the precise manipulation of animal behavior by a microbe. Ophiocordyceps is a fungus that infects zombie ants. Infection of ant workers by thousands of these fungal cells causes the workers to leave the colony and die attached by their mandibles to plants that overhang the trails of ant colonies. There the fungus uses the dead ant bodies to produce spores that infect other ants. The manipulation is complex and spectacular given the fact that an organism without a brain controls the behavior of one with a brain. In this project the research team will use an integrative approach to ask how fungi change ants from being productive members of their colony to "fungi in ant's clothing?". The project will use measurement of gene expression, metabolism and tissue structure to ask how, during the 3 week period of infection, the fungi effectively take control of the ant. This work will provide many general insights into the nature of parasitism and may have broader societal relevance because these fungi are known to be important sources of small molecules with medical relevance. The work is relevant to the broader mission of NSF to increase scientific literacy as the zombie ant system has been shown to be a very useful tool for communicating the elegance and beauty of natural systems.

How can a microbe control the central nervous system of an animal? Animals are intimately associated with microbes that span the symbiotic spectrum from mutualism to parasitism. In some cases, microbial parasites of animals have evolved to control animal behavior in ways that enhance parasite transmission. The zombie ants represent one prominent example. In this system a fungal parasite (Ophiocordyceps unilateralis) has evolved a precise level of behavioral control over the ants it infects. Worker ants infected by O. unilateralis move out from their colonies at precise times of day to highly specific locations on leaves in forests, where they bite into vegetation before dying. This altered behavior provides a platform for the eventual release of spores from a long fungal stalk that grows from the cadaver of the ant. This striking system involves an organism in one kingdom of life (Fungi) that controls the behavior of an organism in another (Animalia). How does an organism without a brain control the behavior of one with a brain? The investigators will address this using time series infectionstudies to measure chemical changes in both the parasite and its host. By using three different but complementary tools (serial block face scanning electron microscopy, metabolomics and transcriptomics) to examine these changes across time, the investigators hope to understand the basis of these behavioral changes.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Emilia Solá Gracia , Charissa de Bekker, Ephraim M. Hanks, David P. Hughes "Within the fortress: A specialized parasite is not discriminated against in a social insect society" PloS One , 2018 https://doi.org/10.1371/journal.pone.0193536
Maridel A. Fredericksen, Yizhe Zhang, Missy L. Hazen, Raquel G. Loreto, Colleen A. Mangold, Danny Z. Chen and David P. Hughes "Three-dimensional visualization and a deep-learning model reveal complex fungal parasite networks in behaviorally manipulated ants" PNAS , 2017 https://doi.org/10.1073/pnas.1711673114
Yizhe Zhang, Lin YangJianxu ChenMaridel FredericksenDavid P. HughesDanny Z. Chen "Deep Adversarial Networks for Biomedical Image Segmentation Utilizing Unannotated Images" International Conference on Medical Image Computing and Computer-Assisted Intervention , 2017 doi: 10.1007/978-3-319-66179-7_47

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

A dramatic phenomenon in nature is the ability of fungal parasites to control ants climb vegetation to bite hard into leaves and twigs before being killed. This gruesome mind control is adaptive for the fungus because it must grow from the dead body of the ant and the death grip behavior it induced means it has secured a safe place to grow and ultimately launch spores from that infect other ants. This is the zombie ant system.

In our NSF project we set out to understand how this happens. We were particularly interested in the difference between fungi, which are microscopic and the ants that they control which are not only multicellular animals but occur in large cohesive societies. We wanted to know how the organism without the brain controls the one with the brain.  We took a multidisciplinary approach that integrated behavioral studies, micro-scale histology with Serial Block Face SEM, standard SEM, immunofluorescence confocal microscopy, metabolomics and transcriptomics. We found that at the time of manipulation, when the ant is manipulated to bite, the fungal parasite has arranged itself into a complex 3D network that surrounds and penetrates the host cells. Surprisingly the fungal cells do not enter the brain of the ant. We did find however the brain of zombie ants are very different to those of healthy ants. We found that the fungus injects specialized compounds into the brain of the ant and the brain has a very distinct chemical signatures, dominated by neuromodulator changes and oxidative reductive processes. We suggest that the zombie ant fungus manipulates its ant host from the periphery, carefully manipulating the muscles while preserving the brain intact, presumably because that is necessary for the full successful behavioral manipulation. Zombie ants are apparently like zombies in human fiction- the brain is critical.

 


Last Modified: 03/19/2019
Modified by: David Hughes

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