Research
We use Drosophila melanogaster to study the mechanisms by which evolutionarily conserved families of genes impact neuronal function and organismal behavior. Although the brains of flies and humans are quite distinct, many important neuronal genes have conserved molecular and physiological functions across these species. In fact, the functions of many neuronal genes were first identified in flies, and later found to be conserved in mammals.
We are currently working on an NSF funded project to understand how ion channels and transporters found in glial cells regulate neuronal activity and animal behavior, especially in the context of environmental stresses, such as fluctuating temperature. We can selectively manipulate the expression levels of a gene in a specific glial subtype, and study how this impacts surrounding neurons!
The variety and ease of genetic tools available to manipulate the genes of Drosophila melanogaster make it a great model organism. In addition to other genetic techniques, we use CRISPR/Cas9 gene editing to create GFP tagged proteins that allow us to assess subcellular localization. Pictured: GFP tagged potassium channel in axons of the adult ventral nerve cord. Hill et al., PLoS Genetics, 2019
In Drosophila, assays have been developed for embryonic, larval and adult stages, to assess a variety of behaviors, including locomotion, reproduction, aggression and even learning and memory! We also use seizure susceptibility assays to study gene environment interactions that affect nervous system homeostasis.
We have recently started looking at the origination of nervous system controlled movements during embryogenesis. We can manipulate specific genes, and then use a microscope to record and analyze embryo movement at different stages of development!
Another focus of the lab is on the non-voltage gated ion channel family of Degenerin/Epithelial sodium channels (DEG/ENaCs), which are found in species throughout the animal kingdom. These channels are found in diverse cell types, including in the nervous system. Some of the human genes encoding DEG/ENaC subunits are associated with neurologic and psychiatric diseases, suggesting that they play a critical role in the nervous system. We use a combination of genetic, molecular and behavioral techniques to study the mechanisms by which Deg/ENaCs impact neuronal function and organismal behavior.
Deg/ENaCs appear to be present at both the pre and postsynaptic sides of synapses, but their specific functions on each side are not well understood. In Drosophila we can easily manipulate pre or postsynaptic expression of Deg/ENaCs to study how they influence synaptic activity.
We previuosly showed that one specific Deg/ENaC subunit, ppk29, is expressed in muscle cells, and impacts neurotransmission at the neuromusuclar junction as well as motor behaviors. Hill et al., J. Neurosci, 2017