{"id":2,"date":"2019-01-25T22:45:06","date_gmt":"2019-01-25T22:45:06","guid":{"rendered":"https:\/\/my.vanderbilt.edu\/mbgd\/?page_id=2"},"modified":"2021-07-29T20:18:43","modified_gmt":"2021-07-29T20:18:43","slug":"sample-projects","status":"publish","type":"page","link":"https:\/\/my.vanderbilt.edu\/mbgd\/sample-projects\/","title":{"rendered":"Projects"},"content":{"rendered":"

Ongoing Projects<\/strong><\/h2>\n

1) G6PC\u00a0and\u00a0SLC37A4 mutants in Glycogen storage Diseases (Derek Claxton and Jonathan Sheehan in collaboration with Richard O’Brien)<\/strong><\/p>\n

Glucose 6-phosphatase catalyze the metabolic pathway of hydrolyzing glucose-6-phosphate (G6P) to glucose and inorganic phosphate. Literature survey suggests that insulin and other hormones and metabolites regulate glucose-6-phosphatase gene expression. Increased enzyme activity contributes to the increased Hepatic Glucose Production associated with diabetes. Glucose-6-phosphatase exists as a multicomponent enzyme system composed of a glucose-6-phosphatase catalytic subunit (G6PC), a G6P\/Pi antiporter (SLC37A4) and microsomal glucose transporter and a microsomal glucose transporter. The catalytic G6PC exists in three isoforms (G6PC1-3). G6PC1 functionally couples to the SLC37A4 antiporter to hydrolyze G6P. Mutations in G6PC1 that reduce enzyme activity cause Glycogen Storage Disease (GSD) type 1a which is characterized by severe hypoglycemia. This project proposes to obtain a detailed structural and molecular understanding of the mechanisms underlying the catalytic function of G6PC1.<\/p>\n

\"G6PC1\"<\/p>\n

The glucose-6-phosphatase system (Newman WG et.al.,<\/em> 2013)<\/div>\n

Our goals are to heterologously express and purify G6PC1 while retaining functional activity, to characterize the biophysical activity of the enzyme and do structural analysis through crystallography and cryo-EM.<\/p>\n

2) Structure and Mechanism of disease-linked mutants of NMDA receptors<\/strong>\u00a0(Brinda Selvaraj in collaboration with Erkan Karakas).<\/strong><\/p>\n

NMDAR (N-methyl-D-aspartate Receptors) mediate the majority of excitatory synaptic neurotransmission throughout the central nervous system and are key players in synaptic plasticity, which is important for learning and memory. NMDARs form heterotetrameric assemblies typically composed of two GluN1 and two GluN2 (A-D) subunits. Neurodegenerative disorders, chronic pain, stroke and schizophrenia have all been attributed to the dysfunction of NMDA receptors. Over-activation of NMDA receptors is excitotoxic and contributes to neuronal damage after stroke or traumatic Injury. Furthermore, chronic NMDA receptor hyperactivity gives rise to the loss of neurons associated with Huntington\u2019s, Parkinson\u2019s and Alzheimer\u2019s diseases.<\/p>\n

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