Lauren A. O'Connell, PhD - US grants

South American poison frogs are brightly colored and highly toxic, advertising their unpalatabilily to potential predators. Poison frogs do not make these toxins themselves, but instead acquire toxins from the ants and mites they consume in their diet. Although scientists have long known that poison frogs accumulate toxins from their diet, how the frogs accumulate the toxic chemicals is unknown. The goal of this research is to understand how poison frogs accumulate and move toxins from the gut through the liver and to the skin for storage. Describing this process will increase our knowledge of how animals have evolved special physiological mechanisms to acquire new resources from their environment. As many of these toxins and other frog chemicals are small molecules similar to many pharmaceutical drugs, understanding how poison frogs transport these chemicals may yield more general insights about how this process is different from other animals (including mammals), which cannot accumulate these compounds. This research will provide learning experiences to all age groups in both the United States and in Ecuador, where fieldwork on poison frogs will be conducted. This award is co-funded by the NSF Office of International Science and Engineering. Research will be incorporated into science K-12 classrooms through the Little Froggers School Program, which teaches children about ecology and evolution. High school biology teachers will be involved in fieldwork in Ecuador and will incorporate their research findings into their science curriculum. This research will also involve training of undergraduate, graduate, and postdoctoral students in chemistry, ecology, proteomics, and bioinformatics.

Poison frogs acquire chemical defenses from dietary arthropods and have evolved specialized physiological adaptations for toxin bioaccumulation and modification. Although sequestering defensive chemicals is one component of well-studied ecological and evolutionary relationships between arthropod prey and frog predators, the mechanisms used by poison frogs to sequester and modify toxins are largely unknown. The overall goal of this research is to understand the physiological mechanisms of toxin bioaccumulation in poison frogs through three aims: 1) Identify proteins involved in bioaccumulation of dietary toxins in the Little Devil frog using thermal proteome profiling. 2) Determine toxin pharmacokinetics in distinct genetic backgrounds of the Little Devil frog using captive feeding experiments and liquid chromatography mass spectrometry across several time points. 3) Test the hypothesis that different Little Devil frog populations have local adaptations to efficiently accumulate chemicals found in local arthropod prey by characterizing population differences in toxin-binding protein abundance using tandem liquid chromatography mass spectrometry. Together, this work will test whether variation in toxin-binding protein levels is due to genetic differences between populations, response to dietary toxin availability, or a combination of both genetic and environmental contributions. This research will more broadly add to the knowledge of how ecological resources shape animal physiology.

Project Summary Infants communicate to their caregivers that they need food by crying. This represents our very first social interaction that lays the foundation for a healthy life by acquiring nutrition for growth and establishing a strong social bond with caregivers. Infants that cannot regulate their nutrition are at risk for malnourishment or obesity, whose deleterious effects will negatively impact the wellness of these individuals for their lifetime. Abnormalities in social recognition and communication, like those found in autism spectrum disorders, also become apparent during infancy. Despite the critical importance of infants communicating nutritional need to caregivers, the neuronal basis remains unknown. To address this deficit, I propose to study social tadpoles that beg their parents for food by dancing. Tadpoles use this begging display to encode nutritional state, enabling us to quantify hunger- based communication. These tadpoles are translucent, allowing us to visualize the development and activity of neurons in the brain. I am combining this novel model system and behavioral paradigm with advanced neurogenetic tools to interrogate the neuronal substrates of hunger-based communication. I will examine whether nutritional quality influences the development of neurons that regulating feeding and communication with in vivo brain imaging. I will also test for a functional role of these neuronal cell-types in begging behavior using a high throughput behavior assay, whole brain clearing and immunohistochemistry, and cell-specific manipulations of neuronal activity. As social recognition is important for establishing parent-offspring bonds, I will then use in vivo neural activity imaging to determine how tadpoles recognize their parents using multi-modal sensory integration. Completion of these experiments will transform our understanding of a social behavior critical for infant survival and life-long wellbeing. There is a pressing need for this research because there are currently no established models for studying the neural mechanisms of infant communication of hunger. This work is important to public health because some of the most prevalent disorders afflicting children in the United States are eating related disorders and conditions involving abnormalities in social recognition and communication, such as autism spectrum disorders. More research on infant feeding and communication is needed to better understand these pathologies in the youngest members of our society.

Project Summary Infants communicate to their caregivers that they need food by crying. This represents our very first social interaction that lays the foundation for a healthy life by acquiring nutrition for growth and establishing a strong social bond with caregivers. Infants that cannot regulate their nutrition are at risk for malnourishment or obesity, whose deleterious effects will negatively impact the wellness of these individuals for their lifetime. Abnormalities in social recognition and communication, like those found in autism spectrum disorders, also become apparent during infancy. Despite the critical importance of infants communicating nutritional need to caregivers, the neuronal basis remains unknown. To address this deficit, I propose to study social tadpoles that beg their parents for food by dancing. Tadpoles use this begging display to encode nutritional state, enabling us to quantify hunger- based communication. These tadpoles are translucent, allowing us to visualize the development and activity of neurons in the brain. I am combining this novel model system and behavioral paradigm with advanced neurogenetic tools to interrogate the neuronal substrates of hunger-based communication. I will examine whether nutritional quality influences the development of neurons that regulating feeding and communication with in vivo brain imaging. I will also test for a functional role of these neuronal cell-types in begging behavior using a high throughput behavior assay, whole brain clearing and immunohistochemistry, and cell-specific manipulations of neuronal activity. As social recognition is important for establishing parent-offspring bonds, I will then use in vivo neural activity imaging to determine how tadpoles recognize their parents using multi-modal sensory integration. Completion of these experiments will transform our understanding of a social behavior critical for infant survival and life-long wellbeing. There is a pressing need for this research because there are currently no established models for studying the neural mechanisms of infant communication of hunger. This work is important to public health because some of the most prevalent disorders afflicting children in the United States are eating related disorders and conditions involving abnormalities in social recognition and communication, such as autism spectrum disorders. More research on infant feeding and communication is needed to better understand these pathologies in the youngest members of our society.