Adaptation of Proteins: Nature Plus Nurture

了解温度敏感蛋白如何在经历广泛不同温度的生物体中稳定，对基础科学和应用科学都具有重要意义。pi将研究在温度适应中起主要作用的两种类型的变化。首先，将研究蛋白质氨基酸序列的变化（它们的“性质”）。通过确定适应性取代在不同热适应物种的蛋白质中发生的位置，pi将更深入地了解蛋白质序列的特定改变如何影响分子的结构和功能，以及这些适应性变化如何帮助建立环境耐受极限。仅仅几度的温度变化就足以扰乱蛋白质并影响有机体的分布模式——这一发现对全球变暖模型具有明确的含义。此外，对进化过程如何改变蛋白质稳定性的理解将有助于生物技术学家为蛋白质稳定性的实验室工程制定策略。蛋白质的稳定性也受到细胞中浸泡蛋白质的小分子和水的影响。pi将研究蛋白质所处的水介质如何帮助“培养”蛋白质以增强其稳定性。新型稳定溶质的发现可以促进生物技术专家开发新型解决方案，用于长期、安全储存药物、细胞和组织。

Somero 9727721 Understanding how temperature-sensitive proteins are stabilized in organisms that experience widely different temperatures has significance for both basic and applied science. The PIs will examine two types of changes that play major roles in temperature adaptation. First, changes in amino acid sequences of proteins (their "nature") will be investigated. By determining where adaptive substitutions occur in proteins of differently thermally-adapted species, the PIs will gain a deeper understanding of how specific alterations of protein sequence affect the molecules' structure and function, and how these adaptive changes help to establish environmental tolerance limits. Temperature changes of only a few degrees centigrade are adequate to perturb proteins and affect organismal distribution patterns-a finding with clear implications for models of global warming. Furthermore, an understanding of how evolutionary processes alter protein stability will assist biotechnologists in developing strategies for laboratory-engineering of protein stability. Protein stability is also influenced by the small molecules and water that bathe proteins in cells. The PIs will investigate how the aqueous medium in which a protein functions helps to "nurture" the protein to enhance stability. Discovery of novel stabilizing solutes could facilitate development by biotechnologists of new types of solutions for the long-term, safe storage of drugs, cells, and tissues.