Coping with stress: the cellular maintenance of embryonic development

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.