CAREER: The Impact of Aneuploidy on Transcription: A Mechanistic Approach

非整倍体是一种染色体拷贝数异常的现象，在进化和自然界中普遍存在。 对于细胞来说，非整倍体既有积极的影响，也有消极的影响。 非整倍性改变转录，但驱动这些变化的机制尚不清楚。 强大的酵母模式生物将被用来确定潜在的分子机制，使用染色质免疫沉淀，下一代测序和计算分析的组合。 了解这些机制将提供巨大的洞察力，不仅是非整倍体，而且一般的转录调控。 该项目将导致更好地了解非整倍体的成本和效益。 更广泛的影响一个类似的跨学科的方法将被用来建立一个夏季本科生合成生物学研究计划，并开发一个互动的小说工具，用于教学负责任的研究行为。 科学理解的巨大飞跃往往来自于那些无视传统学科界限，坚持不懈地追求手头问题的人。 在这项提案中，PI试图通过科罗拉多大学国际基因工程机器（iGEM）团队的发展，将这一理念灌输给几代本科生。 这个合成生物学竞赛将学生聚集在一起，度过一个密集的夏天，设计和构建独特的生物电路。 此外，PI试图通过开发一个互动的小说游戏，将学科前的哲学引入到负责任的研究教学中。 这个游戏不仅将以一种参与和互动的方式训练科学家，而且还将使人们能够研究同伴压力如何影响道德行为。 培养诚实、聪明、有创造力的科学家的长期影响是无法估量的。

Aneuploidy, an abnormal chromosome copy number, is common in evolution and nature. For the cell, there are both positive and negative effects of aneuploidy. Aneuploidy alters transcription but the mechanisms driving these changes are not understood. The powerful yeast model organism will be utilized to ascertain the underlying molecular mechanism using a combination of chromatin immunoprecipitation, next-generation sequencing, and computational analysis. Understanding these mechanisms will provide tremendous insight into not only aneuploidy but also transcriptional regulation in general. This project will lead to a better understanding of the costs and benefits of aneuploidy. Broader Impact A similar cross-disciplinary approach will be utilized to build a summer undergraduate research program in synthetic biology and develop an interactive fiction tool for teaching responsible conduct of research. Tremendous leaps in scientific understanding often arise from individuals who ignore traditional disciplinary boundaries to relentlessly pursue the question at hand. In this proposal, the PI seeks to instill this philosophy into generations of undergraduates through the development of a University of Colorado internationally Genetically Engineered Machines (iGEM) team. This synthetic biology competition brings students together for an intensive summer to design and construct unique biological circuits. Additionally, the PI seeks to bring the ante-disciplinary philosophy to teaching responsible conduct of research by developing an interactive fiction game. This game will not only train scientists in an engaging and interactive manner but also will enable studies into how peer pressure influences ethical behavior. The long term impact of creating honest, intelligent, and creative scientists is incalculable.