C. elegans to study organismal control of recovery from bacterial infections

线虫研究细菌感染恢复的有机控制

基本信息

批准号：
9027974
负责人：
Alejandro Aballay
金额：
$ 39.46万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-11-05 至 2020-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9027974
关键词：
Ablation Acute American Society of Hematology Animals Antibiotic Therapy Antibiotics Bacterial Infections Biological C. elegans genome Caenorhabditis elegans Cells Collaborations Computer Simulation Disease Dissection Drug Metabolic Detoxication Endocrine Exhibits Failure G Protein-Coupled Receptor Signaling G-Protein-Coupled Receptors Gene Expression Profiling Genes Genetic Homeostasis Immune response Immune system Immunity Infection Inflammation Inflammatory Laboratories Lead Ligands Link Mediator of activation protein Metabolism Modeling Natural Immunity Nature Nematoda Nervous System control Nervous system structure Neurons Neuropeptides Neurosecretory Systems Neurotransmitters Organism Oxidation-Reduction Pathway interactions Pharmaceutical Preparations Phase Physiological Physiological Processes Physiology Proteins Publishing Recovery Recurrence Regulation Resolution Role Signal Transduction Signaling Molecule Surface Synapses System Technology Testing Tissues Universities Virulence Factors Wound Healing Xenobiotics base cell growth regulation chronic autoimmune disease design dopaminergic neuron genetic approach immune activation insight killings microbial mutant neural circuit neuroregulation new therapeutic target optogenetics pathogen promoter protein folding public health relevance receptor-mediated signaling relating to nervous system research study response reverse genetics transcription factor

项目摘要

DESCRIPTION (provided by applicant) This proposal describes experiments designed to understand the mechanisms involved in the control of recovery from bacterial infections. To recover from an infection and return to homeostasis, the host must activate mechanisms capable of controlling the damage caused by pathogen virulence factors, inflammation, and a potentially toxic antibiotic exposure. Failure to properly recover from infections manifests in the form of recurrent infections, inappropriate wound healing, autoimmune diseases, and chronic inflammatory disorders. The mechanisms involved in pathogen recognition and immune activation have been very well studied, but the cellular and systemic responses involved in recovery after an infection is cleared are not well defined. We have established a Caenorhabditis elegans model of acute infection and antibiotic treatment for studying biological changes during the resolution phase of an infection. We found that genes that are markers of innate immunity are downregulated upon recovery, while genes involved in xenobiotic detoxification, redox regulation, and cellular homeostasis are upregulated. Using gene expression profiling, in silico analysis, and reverse genetic approaches, we have linked to the control of recovery from infection to the function of conserved transcription factors, including th GATA transcription factor ELT-2, the FOXO transcription factor DAF-16, and the Nrf transcription factor SKN-1. The proposed experiments will explore the general hypothesis that neural GPCRs and cell non-autonomous signals from different neurons may act on non-neural tissues to regulate recovery from infection at the organismal level. Given the conserved nature of GPCR-mediated signaling and the conservation of the transcription factors involved in the control of recovery, the proposed studies should lead to a better understanding of the mechanisms used by metazoans to control recovery from bacterial infection at the whole animal level.

描述（申请人证明）该提案旨在了解涉及细菌感染的含量的机制。在反复发作的不适，伤口愈合，自身免疫性疾病和慢性炎症疾病{在研究生物学的抗生素治疗中，建立了一种感染的生物学！转录因子ELT-2，FOXO转录因子DAF-16和NRF转录因子SKN-1。神经组织从生物水平的感染中恢复。