CAREER: Molecular mechanisms underlying yeast cellular starvation tolerance; spatial reasoning to increase STEM participation

职业：酵母细胞饥饿耐受性的分子机制；

• 批准号: 1943488
• 负责人: Loren Hough
• 金额: $ 107.6万
• 依托单位: University of Colorado at Boulder
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1943488&HistoricalAwards=false
• 关键词: CAREER; Molecular; mechanisms; underlying; yeast

All organisms must respond to changes in their environment. For example, yeast which grow on grapes must survive drought, sudden rain, and changes in alcohol concentration during fermentation. In response to stress, cells alter the composition and chemical properties of their interior. An outstanding question is how changes in the interior of cells result in protection from stresses. Nuclear magnetic resonance spectroscopy (NMR) is a technique which can give information on the atomic level behavior of proteins within cells. In this research, NMR will be used to measure changes in protein behavior as cells are stressed. In addition, this project will facilitate the training of elementary school teachers and their students in spatial reasoning. Spatial reasoning is broadly defined as the ability to visualize, mentally manipulate, and create representations of complex three- dimensional objects. A widescale cultural misconception is that spatial reasoning skills are immutable; in fact, they are one of the most trainable of STEM-related skills. By targeting elementary school students, this project will serve to increase STEM participation in general and to mitigate disparities in STEM for underrepresented groups. Cells respond to environmental perturbations through wide-scale changes in their intracellular chemical environment, protein localization and dynamics, and global cytoplasmic physical properties. All of these responses are thought to be necessary for cell survival. To reconcile the sensitivity of stress-responsive proteins with the unknown changes in the cellular environment under stress conditions, we require an atomic-scale readout of intracellular protein behavior. In this research, in cell NMR experiments will be used to probe the intracellular environment in budding yeast. Budding yeast have well developed genetic, environmental and pharmacological perturbations that can be used to selectively control aspects of the cellular stress response. Comparisons between solution and cellular protein behavior by NMR will be used to determine how proteins change in cells and how cellular stress further effects proteins. NMR will be used to map atomic-level changes in stress-responsive proteins and a library of protein fragments will be used to determine sequence specificity of stress response. Manipulations of the yeast cells will be used to determine underlying chemical perturbations that lead to those changes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

所有生物都必须对环境的变化作出反应。例如，生长在葡萄上的酵母必须在发酵过程中经受住干旱、骤雨和酒精浓度的变化。作为对压力的反应，细胞改变其内部的组成和化学性质。一个突出的问题是细胞内部的变化是如何导致免受压力的保护的。核磁共振波谱（NMR）是一种可以提供细胞内蛋白质原子水平行为信息的技术。在这项研究中，核磁共振将用于测量细胞受到压力时蛋白质行为的变化。此外，本项目将促进小学教师和学生空间推理能力的训练。空间推理被广泛地定义为对复杂的三维物体进行可视化、心理操作和创造表征的能力。一个普遍的文化误解是空间推理能力是不可改变的；事实上，它们是stem相关技能中最容易训练的技能之一。通过针对小学生，该项目将有助于提高STEM的总体参与度，并减轻代表性不足群体在STEM方面的差距。细胞通过细胞内化学环境、蛋白质定位和动力学以及整体细胞质物理特性的大范围变化来响应环境扰动。所有这些反应都被认为是细胞存活所必需的。为了使应激反应蛋白的敏感性与应激条件下细胞环境的未知变化相协调，我们需要一个细胞内蛋白质行为的原子尺度读数。在本研究中，细胞内核磁共振实验将用于探索芽殖酵母的细胞内环境。芽殖酵母具有良好的遗传、环境和药理学扰动，可用于选择性地控制细胞应激反应的各个方面。通过核磁共振对溶液和细胞蛋白质行为的比较将用于确定蛋白质在细胞中如何变化以及细胞应激如何进一步影响蛋白质。核磁共振将用于绘制应激反应蛋白的原子水平变化，蛋白质片段库将用于确定应激反应的序列特异性。对酵母细胞的操作将用于确定导致这些变化的潜在化学扰动。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。