Collaborative Research: From Molecules to Communities: How Levels of Selection Integrate to Tame Selfish Elements

合作研究：从分子到群体：选择水平如何整合以驯服自私元素

• 批准号: 2151033
• 负责人: Daniel Jarosz
• 金额: $ 102.71万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2151033&HistoricalAwards=false
• 关键词: Collaborative; Research; Molecules; Communities; How

Genes code for an extraordinary diversity of life on earth but in some circumstances, proteins called prions can also replicate across generations. They cause various diseases such as mad cow disease and chronic wasting disease but also sometimes provide beneficial traits. This suggests that some prions have been tamed by their hosts, and even provide a value. In contrast to genes, we understand very little about how evolution acts on prions. This proposal will be the first direct investigation of how natural selection acts on prions. In addition, the work will provide a characterization of the distribution of prion variants in the global yeast population. The project provides broad societal impact through increased understanding of prions which are an important class of emerging disease agents. This information will also allow a better understanding of viral evolution. Further broader impacts arise through the training of numerous undergraduate and graduate scientists, and through educational and outreach activities to the broader public. This proposal takes advantage of the fact that prions can be propagated both inside of cells and in a cell-free environment. Comparing the outcomes of evolution in each of these conditions will allow an examination of how prions are tamed by cells. The proposed research will lead to new insights into how evolution has impacted the origin and maintenance of prion proteins, spanning from the molecular scale to biological communities. The project will focus on one prion, termed [GAR+] and its evolution with and without a yeast host. Expected outcomes include a robust characterization of the multiple selective pressures that influence prion evolution including a comprehensive comparisons of the biological effects of prions evolved within a host or in a cell-free environment. To achieve this the study will employ a replicated experimental evolution of prions in yeast and in cell free chemical environments and will compare the changes between these two environments.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.

基因编码地球上生命的非凡多样性，但在某些情况下，称为朊病毒的蛋白质也可以跨代复制。它们会引起各种疾病，例如疯牛病和慢性消耗性疾病，但有时也提供有益的特征。这表明一些朊病毒已被宿主驯服，甚至提供了价值。与基因相比，我们对进化如何作用于朊病毒知之甚少。该提案将是首次直接研究自然选择如何作用于朊病毒。此外，这项工作还将提供全球酵母菌群中朊病毒变体分布的特征。该项目通过加深对朊病毒（一类重要的新兴疾病病原体）的了解，产生了广泛的社会影响。这些信息也将有助于更好地了解病毒进化。通过对众多本科生和研究生科学家的培训以及对更广泛公众的教育和推广活动，产生了更广泛的影响。该提议利用了朊病毒可以在细胞内部和无细胞环境中繁殖的事实。比较每种条件下的进化结果将有助于检查细胞如何驯服朊病毒。拟议的研究将对进化如何影响朊病毒蛋白的起源和维持（从分子尺度到生物群落）产生新的见解。该项目将重点研究一种名为[GAR+]的朊病毒及其在有或没有酵母宿主的情况下的进化。预期结果包括对影响朊病毒进化的多种选择压力的稳健表征，包括对宿主内或无细胞环境中进化的朊病毒的生物效应的全面比较。为了实现这一目标，该研究将在酵母和无细胞化学环境中采用朊病毒的复制实验进化，并将比较这两种环境之间的变化。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力评估进行评估，被认为值得支持。优点和更广泛的影响审查标准。