Coping with stress: the cellular maintenance of embryonic development

描述（由申请人提供）：环境的突然变化会破坏细胞过程。细胞具有损伤控制机制来应对这些环境“压力”，因此对这种外部侮辱表现出一定的耐受性。但是细胞也很脆弱；环境压力导致细胞缺陷，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，细胞必须执行一套程序化的快速细胞分裂，这在很大程度上依赖于细胞骨架蛋白的作用，而细胞骨架蛋白的结构和功能对环境应激高度敏感。胚胎如何在环境胁迫下维持细胞功能和正常发育？本研究计划的目标是确定黑腹果蝇胚胎体内环境应激耐受的分子和细胞机制。培训将采用创新的方法，强调使用显微镜和发育遗传学技术来确定和操纵胚胎的耐热性。胚胎热应激表型将在细胞分辨率上进行解剖(1)跨多个基因型，(2)在稳定细胞骨架的候选蛋白表达中断的胚胎中，以及(3)在不同热环境中自然分离的野生果蝇中。这项研究将通过促进我们对细胞如何应对环境应激的基本知识，并通过确定在细胞和整个生物体水平上作为应激耐受性基础的候选途径，产生广泛的影响。

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.