Understanding the effects chemical exposure has on neurodevelopment is crucial for protecting human health and improving environmental policies and safety. Our research uses zebrafish to investigate how environmental and chemical exposures influence early development, as their embryos allow us to observe changes across multiple biological levels. Within our collaborative lab structure, research teams work together to examine how various factors affect development from genes to behavior. My role in the lab includes training in zebrafish-based experimental techniques and beginning to conduct literature analysis to identify candidate chemicals for future experiments.
Plants have evolved a sophisticated set of pathways to detect and respond to light, which allows them to adjust their development in response to changing conditions. Red and far-red wavelengths are detected by photoreceptors called phytochromes (phys), with phyB being the major phytochrome involved in red-light response in the model plant Arabidopsis thaliana. Phytochrome levels are regulated by an E3 ubiquitin-ligase complex that includes the target-adaptor Light-Response BTB1 or BTB2 (LRB1 or LRB2) proteins. The Gingerich lab studies lines of Arabidopsis that contain mutations in the LRB1, LRB2, and PHYB genes. Analysis of growth responses to light and other environmental or physiological factors that intersect with light response helps us better understand how the phytochrome pathway regulates development. Here, we present an analysis of germination responses to red and far-red light and seedling development responses to the hormone methyl jasmonate in our lines. Germination response to red and far-red light is well-studied, and recent analyses have suggested roles for phyB in modulating jasmonate responses; thus, studies of these responses in lines with alterations of the phytochrome pathway might be informative.
Rare diseases affect 30 million Americans, many of whom remain undiagnosed due to limited functional characterization of DNA variants. Propionic acidemia is caused by variants in PCCA or PCCB that impair enzyme function, leading to severe metabolic dysfunction, often presenting in early infancy. While the Wisconsin newborn screening panel tests for this disorder, screening is neither 100% effective nor does it identify the cause of propionic acidemia in each patient. There are 979 reported DNA variants of uncertain significance or conflicting classification in PCCA and PCCB, meaning that it is unclear if these mutations cause the disease: thus, identification of one of these variants in a patient does not equal clear diagnosis. To address this gap, our lab uses a minigene system to examine whether variants have functional effects. Although we can effectively assess individual variants with this system, it is a relatively low-throughput method. We present our efforts at optimizing this system through improved sample processing, next-generation sequencing (NGS), and development of efficient R scripts. An improved pipeline should accelerate the resolution of variants of uncertain significance associated both with propionic acidemia and across rare genetic diseases.
Schistosomiasis is a neglected tropical disease that affects over 250 million people worldwide and is caused by parasitic flatworms known as schistosomes. Miracidia, the first larval stage of schistosomes, infect snails as intermediate hosts, where they mature into a larval stage capable of infecting humans. Although it is not definitively known how miracidia locate snails, they have been shown to detect and interpret light to navigate their environment. The purpose of this study was to analyze the movement of Schistosoma mansoni miracidia in response to the presence of light and to different wavelengths of light. Miracidia were loaded onto rectangular arenas and exposed to light gradients, including white, red, blue, and/or green light. The miracidia were recorded for 1 hour and tracked using custom code. As expected, and consistent with previous work, miracidia are photoattracted. Notably, preliminary results indicate that they prefer blue over red light but have no apparent preference between blue and green light. Future experiments will explore the integration of their light and chemical perception. Understanding this sensory coordination could be key to developing new strategies to reduce schistosome populations and the spread of schistosomiasis.
