2017-2018 Beckman Scholars
Elizabeth Rodier “Validation of a cover blocker for epilepsy associated KNCQ2 channels.” (PI: Tzingounis)
Major: Physiology and Neurobiology; Minor: Spanish
Abstract: KCNQ2 potassium channels are critical controllers of neonatal brain activity. A growing number of gain-of-function pathogenic KCNQ2 variants have been reported in patients with severe neonatal epilepsy. Currently there are no specific KCNQ2 channel inhibitors to block the activity of these channels. The goal of my project is to provide insight into the drug “HN38” as a potential treatment for the gain-of-function variants of KCNQ2 potassium channels. I will determine the selectivity of HN38 on KCNQ channel family members, as well as determine whether this drug can inhibit gain-of-function variants identified from pediatric epilepsy patients.
Jessica Young “The role of Jun kinase (JNK) signaling pathway in Drosophila ovulation." (PI: Sun)
Major: Physiology and Neurobiology
Abstract: The Jun Kinase (JNK) signaling pathway has been thoroughly investigated within cell apoptosis and cancer metastasis; however, its role in ovulation has not been studied. I will investigate the role of the JNK signaling pathway using the novel Drosophila ovulation model, which utilizes a conserved cellular and molecular mechanism. Preliminary research performed implicates that the transcription factor Jun is involved in ovulation. Further investigation of other components in the JNK pathway will establish a Drosophila model for understanding the mechanism by which the JNK signaling pathway regulates ovulation and where it exists within the established ovulation signaling pathway.
2016-2017 Beckman Scholars
Brock Chimileski “The neurochemical phenotype of lateral hypothalamic hypocretin/orexin and melanin-concentrating hormone neurons identified through single-cell gene expression profiling and manipulations to metabolic state” (PI: Jackson)
Major: Physiology and Neurobiology/ Molecular and Cell Biology
Abstract: One essential, yet poorly understood, brain region is the lateral hypothalamic area (LHA). The LHA integrates diverse physiological signals to regulate hunger, metabolism, arousal, and motivation. It is comprised of a heterogeneous cell population, but two cell types are of particular significance; the hypocretin/orexin and melanin-concentrating hormone (MCH) neurons, which are named as such because they release either hypocretin/orexin or MCH as their primary neuropeptide. For both of these cell types, many questions still pertain to their precise neurochemical properties and subsequent roles in the neural circuitry that regulate the function of the LHA as a whole. This project attempts to better define the molecular characteristics of these neurons by addressing three questions: 1) What neuropeptides and fast neurotransmitters are co-expressed in these populations, 2) what is the diversity in gene expression within these populations, and 3) are these properties dependent on physiological state?
To investigate these questions, we optimized a single cell isolation method and performed gene expression profiling for 48 key genes in many single hypocretin/orexin and MCH cells. In addition, in-situ hybridization and immunohistochemistry were performed for key markers in coronal brain sections containing the LHA. Additional trials were conducted using mice that underwent 24 hours of food deprivation directly prior to experimentation. This analysis revealed that both of these cell populations have extensive co-expression with other neuropeptides in addition to their primary neuropeptide. Furthermore, they express markers for both excitatory and inhibitory neurotransmitter components, creating the possibility of a dual excitatory/inhibitory fast neurotransmitter phenotype. Experiments with manipulations to physiological state through food deprivation are on-going. Through this detailed characterization of the neurochemical phenotype of Hcrt/Ox and MCH neurons, we hope to further our understanding of their unique roles in the neural circuitry of the LHA modulating behavioral and physiological homeostasis.