UC San Diego SearchMenu
2016 Research Showcase
BABP Abstracts
Abstract Title : Structural Motifs of Ly6h That Facilitate Regulation of Nicotinic Acetylcholine Receptors
Abstract : Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels that contribute to cognition and pathophysiological conditions, such as Alzheimer's disease. We have previously shown that several Ly6 family proteins are able to complex with and modulate nAChR activity. Since all Ly6 proteins are predicted to share a common tertiary structure consisting of a three finger domain, we hypothesized that one or more of these fingers might interact with and regulate nAChR function. To test this, we generated and assayed deletion constructs of Ly6h, an endogenous mammalian Ly6 protein required for normal intracellular trafficking of nAChRs and suppression of nAChR currents in the brain. Our data suggest that loop 3 is required for Ly6h to form stable complexes with α7 nAChRs, and to suppress its function. These studies provide insight into regulation of neurotransmitter receptors by Ly6 proteins and suggest avenues to correct aberrant signaling in disease states.
Abstract Title : The role of TRPV ion channels in regulating scrunching behavior in Dugesia japonica
Abstract : Transient receptor potential (TRP) ion channels are a family of proteins that mediate response to a variety of stimuli in diverse taxa, including humans. The vanilloid TRP (TRPV) receptor responds to noxious stimuli such as capsaicin and heat. Here we show that TRPV mediates a distinct locomotive phenotype in the freshwater planarian Dugesia japonica, called scrunching. This characteristic pain response can be easily quantified by computational image analysis. D. japonica is an effective model organism for the study of TRPV channels and other sensory receptors because their tractable nervous system contains similar neurotransmitters and cell types as those of the vertebrate brain; they also readily absorb chemicals added to their aquatic environment. Thus, our research may aid in the future development of novel pharmaceuticals for pain treatment in humans.
Abstract Title : Homology Modelling and Molecular Dynamic simulation of Plasmodium falciparum GGPPS
Abstract : Malaria, a life threatening disease affecting over 300 million people all over the world, is caused by the parasite Plasmodium spp. Over 2/3rds of the cases reported is caused by the species Plasmodium falciparum and Plasmodium vivax, with falciparum infections being far more lethal than vivax. Due to the genetic makeup of P. falciparum, the crystal structures of its proteins are extremely difficult to obtain, and most in vitro studies are performed with homologous vivax proteins. Therefore, obtaining three-dimensional, atomistic models of falciparum proteins can be of great help to identify new drug leads to treat Plasmodium falciparum infections. Many drug related studies target the Isoprenoid pathway, an important metabolic pathway which forms precursors to essential steroids. In Plasmodium species, one single enzyme appears to be responsible for the synthesis of both farnesyl and geranylgeranyl precursors, which was named Geranylgeranyl Diphosphate Synthase (GGPPS) based on its major product in vitro. Certain bisphosphonate drugs and benzoic acid ligands have been identified as good inhibitors of Plasmodium vivax GGPPS, confirming its potential as a new molecular target to treat malaria. In this work, we built a homology for Plasmodium falciparum (Pf)GGPPS based on the crystal structure of the analogous Plasmodium vivax protein, with which it shares 74% of sequence identity. We then investigated the main motions and dynamic behavior of PfGGPPS by means of molecular simulations, in different apo- and holo-states. Ligands included the natural product, GGPP, and two different inhibitors. Based on these simulations, we identified clusters of representative conformations that differ in terms of backbone conformation (RMSD) and pocket volume. We expect these structures to be valuable in silico models to be used in virtual screenings for potential new antimalaria drugs.