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Epigenetic regulation of hormone action in Tribolium and Aedes

谷盗和伊蚊激素作用的表观遗传调控

基本信息

批准号：
10417159
负责人：
SUBBA R PALLI
金额：
$ 29.87万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10417159
关键词：
Acetylation Adult Aedes Agonist Animals Antibodies Binding Bioinformatics Biological Assay Biological Metamorphosis Biological Models CRISPR/Cas technology Cell Culture Techniques Cells Complex Culicidae Data Deacetylation Development Developmental Process Disease Disease Vectors Ecdysone Ecdysteroids Ecdysterone Endocrinology Ensure Enzymes Epigenetic Process Female Food Genes Genome Goals Growth and Development function Histone Deacetylase Histone-Lysine N-Methyltransferase Histones Homologous Gene Hormone Receptor Hormones Human Insect Control Insect Hormones Insecta Insecticides Juvenile Hormones Knowledge Laboratories Life Ligands Literature Livestock Malignant Neoplasms Mass Spectrum Analysis Mediating Medicine Methods Methoprene Methylation Modeling Modification Molecular Pathway interactions Pest Control Physiological Physiological Processes Plants Play Principal Investigator Process Proteins Publishing RNA Interference Regulation Reporter Reproduction Reproductive Process Research Research Support Response Elements Role Steroid Receptors Testing Tissues Tribolium Vertebrates Western Blotting base chromatin immunoprecipitation demethylation ecdysone receptor enzyme activity epigenetic regulation experimental study gene product genome editing histone acetyltransferase histone demethylase histone modification hormone analog hormone regulation hormone response element human disease insect disease vector mass spectrometer programs promoter receptor receptor binding response success transcription factor transcriptome sequencing vector control yeast two hybrid system

项目摘要

PROJECT SUMMARY There has been a continuous demand for development of insect control methods that are target-specific. Juvenile hormone (JH) and ecdysteroids (20-hydroxyecdysone, 20E is the most active form) are the major hormones that regulate many physiological and developmental processes in insects. Since these hormones are not present in vertebrates, they represent attractive targets for development of insect control methods. Hindering this effort is the lack of understanding on the molecular basis of action of these hormones. There has been excellent recent progress in understanding the molecular basis of 20E and JH action. Key players, including receptors, co-activators, response elements and target genes involved in the action of these hormones have been identified. Non-steroidal ecdysone agonists and JH analogs have been discovered, and commercialized for the control of pests and disease vectors. Research supported by this program showed that epigenetic modifications, especially acetylation levels of histones regulated by histone acetyltransferases (HAT) and histone deacetylases (HDAC) modulate JH and 20E action. Hormone action requires multiple layers of regulation because the same circulating levels of hormones exert diverse functions in different tissues and under different physiological conditions. Based on the published literature and preliminary data included in this application, we hypothesize that epigenetic regulators HDACs, HATs, histone lysine methyltransferases (HKMT) and histone demethylases (HDM) modulate JH and 20E action in the regulation of postembryonic development and reproduction. The main goal of this proposal to test this hypothesis by studying the mechanisms of action of epigenetic modifiers in JH and 20E action using T. castaneum, TcA cells, Ae. aegypti and Aag2 cells as model systems. The two Specific Aims of the proposal are 1. To identify and characterize epigenetic modifiers required for 20E and JH regulation of postembryonic development and female reproduction and 2. To study mechanisms of action of epigenetic modifiers required for 20E and JH regulation of postembryonic development and female reproduction. In the first Specific Aim, RNAi, CRISPR/Cas9 genome editing methods, RNA sequencing, bioinformatics, RT-qPCR, enzyme assays and cell culture approaches will be used to identify and characterize HATs, HDACs, HKMTs and HDMs required for postembryonic development and female reproduction in T. castaneum and Ae. aegypti. In the second Specific Aim, the mechanisms of action of 10-12 epigenetic modifiers will be studied using western blots and ChIP, reporter, Two-hybrid and pull-down assays, and mass spectrometry approaches. Results from the proposed research will impact medicine by providing information for the development of vector control methods. This information could help in understanding epigenetics of human diseases such as cancer. The results from the proposed research may help to transform our understanding of endocrinology of disease vectors.

项目总结