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

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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.