Baker’s yeast (Saccharomyces cerevisiae) has broad genetic homology to human cells. Although typically grown as 1-2mm diameter colonies under certain conditions yeast can form very large (10 + mm in diameter) or ‘giant’ colonies on agar. Giant yeast colonies have been used to study diverse biomedical processes such as cell survival, aging, and the response to cancer pharmacogenomics. Such colonies evolve dynamically into complex stratified structures that respond differentially to environmental cues. Ammonia production, gravity driven ammonia convection, and shear defense responses are key differentiation signals for cell death and reactive oxygen system pathways in these colonies. The response to these signals can be modulated by experimental interventions such as agar composition, gene deletion and application of pharmaceuticals. In this study we used physical factors including colony rotation and microgravity to modify ammonia convection and shear stress as environmental cues and observed differences in the responses of both ammonia dependent and stress response dependent pathways We found that the effects of random positioning are distinct from rotation. Furthermore, both true and simulated microgravity exacerbated both cellular redox responses and apoptosis. These changes were largely shear-response dependent but each model had a unique response signature as measured by shear stress genes and the promoter set which regulates them These physical techniques permitted a graded manipulation of both convection and ammonia signaling and are primed to substantially contribute to our understanding of the mechanisms of drug action, cell aging, and colony differentiation.

中文翻译：

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物理力调节酵母菌群体的氧化状态和应激防御的代谢适应性：太空飞行和微重力模拟。

贝克酵母（Saccharomyces cerevisiae）与人类细胞具有广泛的遗传同源性。尽管通常在某些条件下以直径为1-2mm的菌落生长，但酵母可以在琼脂上形成非常大的菌落（直径为10 + mm）或“巨型”菌落。巨型酵母菌落已用于研究多种生物医学过程，例如细胞存活，衰老以及对癌症药物基因组学的反应。这样的菌落动态演变成复杂的分层结构，对环境线索有不同的反应。氨的产生，重力驱动的氨对流和剪切防御反应是这些菌落中细胞死亡和活性氧系统途径的关键分化信号。可以通过实验干预来调节对这些信号的响应，例如琼脂组成，基因缺失和药物应用。在这项研究中，我们使用包括菌落旋转和微重力在内的物理因素来改变氨对流和切应力作为环境线索，并观察了氨依赖性和应力响应依赖性途径的响应差异。我们发现随机定位的影响与旋转不同。此外，真实的和模拟的微重力都加剧了细胞的氧化还原反应和细胞凋亡。这些变化在很大程度上取决于剪切响应，但是每个模型都有一个独特的响应特征（通过剪切应力基因和调节它们的启动子集来测量）。这些物理技术允许对流和氨信号的分级操纵，并为我们的发展做出了重要贡献了解药物作用，细胞衰老和菌落分化的机制。