While the proportion of people infected with the Human Immunodeficiency Virus (HIV) dying of Acquired Immunodeficiency Syndrome (AIDS) has decreased significantly over the past four decades as antiretroviral therapy has become more common, the full structure of the HIV-1 genome remains unsolved. The 5′ leader of the RNA sequence is of particular interest to solve, as it is the most highly conserved region of HIV’s genome and plays a key role in the packaging and proliferation of the virus. NMR spectroscopy is our lab’s method of elucidating RNA complexes due to its ability to collect data on dynamic complexes in solution. Our group will be using a U1A reporter protein paramagnetically tagged by M8-DOTA-SPy to induce long-range pseudocontact shifts (PCS) in the NMR spectra of our RNA construct. The goal of this project is to elucidate the tertiary structure of the orientation of the TAR and polyA stems of the 5′ leader in relation to each other to build on the Brown et. al paper published in 2020. We will show binding through electrophoretic mobility shift assays (EMSAs) and show PCS of a TAR polyA construct.

Student support provided by the National Institute of General Medical Sciences, National Institutes of Health (NIGMS/NIH) under National Research Service Award T34 GM 136497, NIGMS Initiative for Maximizing Student Development Grant (2R25-GM55036), NIAID grant ##8 R01 AI150498, and the Howard Hughes Medical Institute.

Autism Spectrum Disorder (ASD) is, at once, one of the most common developmental disorders in the world and one of the most debilitating, however, its exact causes remain poorly understood. A preliminary genetic screen has identified the gene CaMKI as a molecular candidate involved in ASD. We hypothesize that mutations in CaMKI would lead to ASD-phenotypes such as sociability deficits and aberrant synaptic refinement. Using Drosophila as a model organism, we genetically ablated CaMKI and used a social assay to measure any resulting social impairment in adult flies, a hallmark of ASD in humans. Additionally, the role of CaMKI in synaptic refinement was tested at the larval neuromuscular junction (NMJ) as well as in the central nervous system. Furthermore, we live-imaged CaMKI-null embryos expressing the genetically encoded calcium indicator GCAMP to examine the activity pattern of the nociceptive class-IV (C4da) sensory cells. Our results suggest that this activity pattern is necessary for the proper development of neuronal networks, so any irregularities provide direct evidence of impeded maturation via synaptic refinement. This study explores the relationship between CaMKI and ASD which casts light on any connection between the disorder and developmental synaptic refinement, as a whole.

This work was funded, in part, through an Undergraduate Research Award from the UMBC Division of Undergraduate Academic Affairs.