Transcriptional Regulation During Oxidative Stress

项目摘要：这个项目直接解决了基本的生物学问题，即基因如何对环境刺激做出反应而开启和关闭。以酵母菌为模型系统，以对氧化应激的反应为刺激。酵母系统允许在活细胞中(在体内)识别和表征重要的角色，然后在机制水平上(在体外)扩展和完善这些研究。这种涉及遗传、分子和生化技术的多学科方法为不同技能水平的学生提供了研究机会。此外，氧化应激反应是一种关键的生理反应，对细胞在富氧环境中的生存极其重要。事实上，氧化应激也与人类的状况高度相关，因为它在衰老、神经退行性疾病和癌症中发挥着基础性作用。为了了解氧化应激反应中的转录主题，该项目探索了两个主要领域：调控因子在氧化应激反应中的作用和单个激活剂可以差异调控广泛的基因的机制(S)。综上所述，这些联合研究将推进对氧化应激转录反应的理解，并将增加对基因如何随着环境变化而开启和关闭的现有知识。除了智力上的优势外，该项目将在至少四个方面产生广泛影响。首先，这些研究的许多方面将为本科生提供合适的项目，他们可能有时间限制以及有限的实验室经验。其次，对技术和时间要求更高的研究将为研究生在许多不同学科(生物化学、遗传学、分子生物学)提供出色的交叉培训经验。重要的是要注意到，这些技术中的大多数都是通用的。学员当然可以利用这些技术来研究其他关键的遗传机制(DNA修复、复制、重组、RNA新陈代谢、表观遗传学等)。在他们未来的职业生涯中。第三，为了推广外展的传统，本科生和研究生都将参与到小学课堂上进行基因表达研究。第四，该项目的成果将在广泛的科学期刊上发表，并在当地和国际会议上展示。总而言之，该项目直接支持国家科学基金会的使命，即促进发现和理解，同时促进教学、培训和学习。

Project Abstract:This project directly addresses the fundamental biological question as to how genes are turned on and off in response to an environmental stimulus. Yeast is used as the model system and the response to oxidative stress as the stimulus. The yeast system allows for the identification and characterization of important players in living cells (in vivo), followed by expansion and refinement of these studies at the mechanistic level (in vitro). This multidisciplinary approach involving genetic, molecular, and biochemical techniques provides research opportunities for students at various skill levels. In addition, the oxidative stress response is a critical physiological response that is extremely important to cell survival in an oxygen-rich environment. Indeed, oxidative stress is also highly relevant to the human condition because it plays fundamental roles in aging, neurodegenerative diseases, and cancer. With the goal of understanding transcriptional themes in response to oxidative stress, this project explores two main areas: the role of regulatory factors in the response to oxidative stress and the mechanism(s) by which a single activator can differentially regulate a wide array of genes. Taken together, these combined studies will advance the understanding of the transcriptional response to oxidative stress, and will add to the current knowledge of the ways in which genes are turned on and off in response to an environmental change.In addition to the intellectual merit, the project will have broad impact in at least four ways. First, many aspects of these studies will provide suitable projects for undergraduate trainees, who may have time constraints as well as limited laboratory experience. Second, studies with higher technical and time demands will provide outstanding cross-training experiences for graduate students in a number of different disciplines (biochemistry, genetics, molecular biology). It is important to note that a majority of these techniques are versatile. Trainees could certainly utilize these techniques to investigate other critical genetic mechanisms (DNA repair, replication, recombination, RNA metabolism, epigentics, etc.) in their future careers. Third, to propagate the tradition of outreach, both undergraduate and graduate students will be involved in taking gene expression studies into elementary school classrooms. Fourth, results from this project will be published in broad based scientific journals, and presented at local and international meetings. Taken together, this project directly supports the mission of the NSF to advance discovery and understanding, while promoting teaching, training and learning.