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Juvenile hormone transporters in disease vector physiology

疾病媒介生理学中的保幼激素转运蛋白

基本信息

批准号：
10658269
负责人：
Naoki Yamanaka
金额：
$ 37.96万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-24 至 2027-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10658269
关键词：
Adult Aedes Arboviruses Biological Biological Assay Biological Models Biology CRISPR/Cas technology Carrier Proteins Cell Line Cell membrane Cells Cellular Membrane Chemicals Chikungunya virus Circulation Culicidae Cultured Cells Cytoplasm Data Dengue Virus Development Diffuse Diffusion Disease Vectors Double-Stranded RNA Drosophila genus Drosophila melanogaster Ecdysone Endocrinology Female Genetic Techniques Geographic Distribution Goals Growth Hormone Receptor Hormones Human Hydrophobicity In Vitro Injections Insecta Juvenile Hormones Lipid Bilayers Liposomes Luciferases Mass Fragmentography Mediating Membrane Membrane Transport Proteins Methodology Modeling Molecular Molecular Genetics Mosquito Control Mutagenesis Mutation Names Organism Orthologous Gene Peripheral Phenocopy Phenotype Physiological Physiology Proteins Quantitative Reverse Transcriptase PCR Reagent Reporter Reproduction Role Techniques Terpenes Textbooks Thyroid Hormones Travel Work Yellow Fever ZIKA combat disorder control global health hormone deficiency human disease in vivo in vivo evaluation inhibitor insect disease vector knock-down lipophilicity loss of function mosquito reproduction mutant novel pharmacologic receptor screening solute steroid hormone tool trafficking transcriptome sequencing vector

项目摘要

PROJECT SUMMARY/ABSTRACT Development and reproduction of insects, including human disease vectors such as mosquitoes, are mainly controlled by two lipophilic hormones: ecdysone and juvenile hormone (JH). Although these hormones need to enter their target cells to exert their biological effects, almost nothing is known regarding molecular mechanisms that regulate hormone transport across cellular membranes. This is due to the prevailing dogma in endocrinology that lipophilic hormones enter and exit cells by simple diffusion across lipid bilayers. However, despite this dominant assumption, the simple diffusion model of lipophilic hormone transport is not supported by any conclusive evidence in any organism. Indeed, recent studies now suggest that some lipophilic hormones, including the insect steroid hormone ecdysone, require membrane transporter proteins to travel across plasma membranes. The overall objective of this project is to identify and characterize membrane transporters required for JH trafficking across cellular membranes, and to thereby challenge the conventional paradigm that lipophilic hormones freely enter and exit cells by simple diffusion. The approach will combine in vitro and in vivo approaches to characterize JH Transporter (JHT), which was discovered in preliminary studies using the fruit fly model system. In Aim 1, functions of the JHT ortholog in the yellow fever mosquito Aedes aegypti, the primary vector for Zika, yellow fever, chikungunya, and dengue viruses, will be thoroughly investigated in vitro using an arsenal of molecular genetic tools. In Aim 2, JHT functions will be further studied genetically in Aedes. As JH controls both growth and reproduction in Aedes and other mosquitoes, characterization of Aedes JHT is expected to aid our effort to combat these deadliest disease vectors for humans. Indeed, in Aim 3, in vitro chemical screening will be conducted to identify compounds that can inhibit functions of Aedes JHT, and their effects will be tested in vivo. The significance of this project is therefore not just to overturn the long-standing dogma in endocrinology, but also to provide a critical proof of concept as well as seed compounds for developing novel pharmacological tools to control mosquitoes and other deadly disease vector insects.

项目总结/文摘