Consequences of Cell Death in Drosophila

果蝇细胞死亡的后果

基本信息

批准号：
9276443
负责人：
Tin Tin Su
金额：
$ 6.39万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9276443
关键词：
Address Angiopoietins Apoptosis Apoptotic Biological Candidate Disease Gene Caspase Cell Death Cell physiology Cells Clinical Complement Cytotoxic Chemotherapy Cytotoxic agent Data Drosophila genus Drosophila melanogaster Ensure Epithelium Experimental Models Exposure to Funding Future Genetic Genetic Screening Goals Health Homeostasis Homologous Gene Human Induction of Apoptosis Ionizing radiation Knowledge Larva Learning Ligands Link Malignant Neoplasms Mammals Mediating MicroRNAs Modeling Molecular Mus Operative Surgical Procedures Outcome Pathway interactions Platelet-Derived Growth Factor Production Protein Isoforms Proteins Publishing Radiation Radiation therapy Receptor Protein-Tyrosine Kinases Resistance Role Signal Pathway Signal Transduction System TP53 gene Testing Tissues Vascular Endothelial Growth Factors base cancer radiation therapy cancer therapy cell killing chemotherapeutic agent chemotherapy clinical practice clinically relevant combinatorial cytotoxic cytotoxic radiation design gene function gene product genetic analysis improved innovation ionization killings novel protective effect research study response standard of care tool

项目摘要

DESCRIPTION (provided by applicant): Ionization radiation (IR) is a major treatment module for cancer because of its ability to induce cell death. Understanding mechanisms that make cells more or less sensitive to killing by IR is an essential first step towards making radiotherapy more effective. The goal of this proposal is to understand one such mechanism. Specifically, the proposal will address a mechanism by which dying cells protect nearby cells from IR-induced apoptosis, using Drosophila as a model. Preliminary studies have uncovered two key players in this mechanism, a receptor tyrosine kinase (RTK) and a microRNA. The goal of this funding period is to identify additional molecular components, in order to reach a complete understanding of this novel effect of dying cells. The Aims are: 1. Investigate whether candidate gene products that underlie the protective effect are required in dying cells or in protected cells 2. Identify the signal that activates the RTK. 3. Identify the remaining components of the signaling pathway in a forward genetic screen. The impact of this project will be the advancement of the field through a molecular understanding of a novel response to cell death. Another potential impact could be the identification of a similar response in clinically relevant mammalian systems in future studies. If conserved in human, a mechanism by which dying cells render nearby cells more resistant to IR could have profound clinical implications, especially in settings where radiotherapy is applied sequentially with cytotoxic chemotherapy.

描述（由申请人提供）：电离辐射（IR）是癌症的主要治疗模块，因为它能够诱导细胞死亡。了解使细胞对红外线杀伤更加敏感或不敏感的机制是使放射治疗更加有效的重要第一步有效的。该提案的目标是了解这样一种机制。具体来说，该提案将以果蝇为模型，探讨垂死细胞保护附近细胞免受红外线诱导的细胞凋亡的机制。初步研究发现了该机制中的两个关键角色，即受体酪氨酸激酶 (RTK) 和 microRNA。该资助期的目标是确定其他分子成分，以便全面了解死亡细胞的这种新效应。目标是： 1. 研究濒死细胞或受保护细胞是否需要构成保护作用的候选基因产物 2. 识别激活 RTK 的信号。 3. 在正向遗传筛选中鉴定信号通路的剩余成分。该项目的影响将是通过对细胞死亡的新反应的分子理解来推动该领域的进步。另一个潜在的影响可能是在未来的研究中在临床相关的哺乳动物系统中识别出类似的反应。如果在人类中得到保留，垂死细胞使附近细胞对IR更具抵抗力的机制可能具有深远的临床意义，特别是在放射治疗与细胞毒性化疗相继应用的情况下。