Coping with stress: the cellular maintenance of embryonic development

应对压力：胚胎发育的细胞维持

• 批准号: 8598910
• 负责人: Brent L. Lockwood
• 金额: $ 3.51万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-12 至 2014-08-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8598910
• 关键词: Actins; Affect; Aging; Alzheimer' s Disease; Animals; Biology; Candidate Disease Gene; Cell Respiration; Cell division; Cell physiology; Cells; Cellular Stress; Chromosome Mapping; Complex; Confocal Microscopy; Cytoskeletal Proteins; Cytoskeleton; DNA; Defect; Development; Developmental Biology; Developmental Process; Disease; Drosophila genus; Drosophila melanogaster; Embryo; Embryonic Development; Environment; Evolution; Exhibits; Exposure to; Future; Genes; Genetic; Genetic Variation; Genotype; Goals; Health; Heat shock proteins; Heating; Human; Image; Knowledge; Life; Link; Maintenance; Maternal Messenger RNA; Measures; Messenger RNA; Methods; Microscopy; Molecular; Molecular Chaperones; Natural Selections; Neurodegenerative Disorders; New Hampshire; North Carolina; Organism; Oxidative Stress; Parkinson Disease; Pathology; Pathway interactions; Phenotype; Physiological; Physiology; Population; Production; Protein Biosynthesis; Proteins; Reactive Oxygen Species; Research; Resolution; Shapes; Staging; Staining method; Stains; Stress; Structure; Surveys; Survival Rate; System; Techniques; Temperature; Testing; Training; Transgenic Organisms; Tubulin; Variant; Whole Organism; Work; Zimbabwe; base; comparative; coping; developmental genetics; experience; fitness; in vivo; innovation; knowledge of results; maternal stress; professor; programs; response; stress protein; stress tolerance; therapy development; thermal stress

DESCRIPTION (provided by applicant): Sudden changes in the environment can disrupt cellular processes. Cells possess damage-control mechanisms to cope with these environmental "stresses", and thus exhibit some tolerance to such external insults. But cells can also be quite vulnerable; environmental stress causes cellular defects that are the basis of certain neurodegenerative diseases and aging. In the context of embryonic development, cells must execute a programmed set of rapid cell divisions, which are largely dependent on the action of cytoskeletal proteins whose structures and functions are highly sensitive to environmental stress. How do embryos maintain cellular function and normal development in the face of environmental stress? The goal of this research program is to identify the molecular and cellular mechanisms that underlie tolerance to environmental stress in vivo in Drosophila melanogaster embryos. The training will take an innovative approach by emphasizing the use of techniques in microscopy and developmental genetics to define and manipulate embryonic thermal tolerance. The embryonic thermal stress phenotype will be dissected at cellular resolution (1) across multiple genotypes, (2) in embryos with disrupted expression of candidate proteins that stabilize the cytoskeleton, and (3) among natural isolates of wild Drosophila from distinct thermal environments. This research will have a broad impact by contributing to our basic knowledge of how cells respond to environmental stress and by identifying candidate pathways that are the basis of stress tolerance at both the cellular and whole-organism levels.

描述（由申请人提供）：环境的突然变化可能会破坏细胞过程。细胞具有损伤控制机制来科普这些环境“压力”，因此对这种外部损伤表现出一定的耐受性。但细胞也可能非常脆弱;环境压力会导致细胞缺陷，这是某些神经退行性疾病和衰老的基础。在胚胎发育的背景下，细胞必须执行一组程序化的快速细胞分裂，这在很大程度上取决于细胞骨架蛋白的作用，其结构和功能对环境应激高度敏感。胚胎如何在环境压力下保持细胞功能和正常发育？本研究计划的目标是确定果蝇胚胎体内环境应激耐受性的分子和细胞机制。培训将采取创新的方法，强调使用显微镜和发育遗传学技术来定义和操纵胚胎耐热性。胚胎热应激表型将在细胞分辨率下进行剖析（1）在多个基因型中，（2）在具有稳定细胞骨架的候选蛋白质的表达被破坏的胚胎中，以及（3）在来自不同热环境的野生果蝇的天然分离株中。这项研究将产生广泛的影响，有助于我们对细胞如何应对环境压力的基本知识，并确定在细胞和整个生物体水平上作为压力耐受基础的候选途径。