Mechanisms of Mitochondrial Repeat-Mediated Deletion

智力优势：大多数真核细胞含有线粒体，这是一种为细胞产生能量的膜结合细胞器。除了在细胞核中发现的DNA外，线粒体还含有DNA。线粒体DNA的忠实维护对细胞的正常功能至关重要。线粒体DNA大片段的缺失在许多类型的细胞中都是常见的突变。在人类中，这些突变随着年龄的增长而积累，并与遗传性疾病综合征有关。这种类型的缺失也通常在面包酵母的线粒体DNA中观察到。这个项目的长期目标是了解这些缺失产生的机制，使用酵母作为模型系统。研究人员的目标是了解参与这一过程的蛋白质及其活动。研究人员设计了遗传策略来研究这些因素，以研究导致线粒体缺失的蛋白质，确定哪些蛋白质与线粒体DNA的双链断裂结合，并研究线粒体双链断裂修复中的时间事件。这项工作的完成将为线粒体DNA代谢的广泛领域提供新的信息，包括复制、重组和修复。更广泛的影响：这项工作将在几个方面对生物科学本科生的教育产生积极的影响。在过去的5年里，首席研究员指导了17名从事独立项目的本科生。酵母研究非常适合缺乏经验的本科生，使他们能够在夏季或学期中学习大量的技术和概念。此外，这项研究代表了与纽约州立大学布罗克波特分校的联合首席研究员的合作，这是一所不授予博士学位的四年制大学。生物科学系为本科生的研究提供了极好的机会。更重要的是，在过去的5年里，联合首席研究员的记录支持了布罗克波特生物科学系进一步参与研究的目标。联合首席研究员共资助了15名本科生和7名硕士生进行各种独立研究和指导研究项目，其中3名是CSTEP/McNair学者。研究人员将继续履行对科学教育的承诺，并让纽约州立大学布罗克波特分校和罗切斯特大学的生物学专业本科生参与目前的项目。首席研究员和联合首席研究员都改编了几个小项目用于实验课程。练习已经设计纳入标准酵母遗传方法和酵母双杂交技术教学实验室。学生们用与目前在首席研究员和联合首席研究员实验室进行的研究相关的诱饵进行筛选。

Intellectual Merit: Most eukaryotic cells contain mitochondria, the membrane-bound organelles that produce energy for the cell. In addition to DNA found in the nucleus of the cell, mitochondria contain DNA. The faithful maintenance of the mitochondrial DNA is essential to the normal function of cells. Deletions of large segments of the mitochondrial DNA are common mutations in many types of cells. In humans, these mutations accumulate with age and are associated with inherited disease syndromes. Deletions of this type are also commonly observed in the mitochondrial DNA of baker's yeast. The long-term goal of this project is to understand the mechanism by which these deletions arise using yeast as a model system. The researchers aims are directed at understanding the proteins involved in this process and their activities. The researchers have devised genetic strategies to study these factors to study the proteins that contribute to mitochondrial deletions, determine what proteins bind to double-strand breaks in mitochondrial DNA, and study the temporal events in mitochondrial double-strand break repair. Completion of this work will provide new information on the broad area of mitochondrial DNA metabolism, including replication, recombination and repair.Broader impacts:This work will have a positive impact in the education of undergraduates in the biological sciences in several ways. In the past 5 years, the principal investigator has mentored 17 undergraduate students pursuing independent projects. Studies with yeast are well suited to undergraduates with little experience, allowing them to learn a large number of techniques and concepts in a summer or semester. In addition, the research represents a collaboration with the co-principal investigator at SUNY-Brockport, which is primarily a 4-year institution that does not grant Ph.D. degrees. The Department of Biological Sciences provides excellent opportunities for undergraduate research. More to the point, the record of the co-principal investigator over the past 5 years has supported the goal of the Department of Biological Sciences at Brockport to further undergraduate involvement in research. The co-principal investigator has sponsored a total of 15 undergraduates, and 7 Master's students in a variety of independent studies and directed research projects, 3 of those were CSTEP/McNair Scholars. The researchers will continue to honor this commitment to scientific education with the involvement of undergraduate biology majors at SUNY Brockport and the University of Rochester in the current project. Both the principal investigator and the co-principal investigator have adapted several small projects for use in laboratory courses. Exercises have been designed that incorporate standard yeast genetic approaches and yeast two-hybrid techniques to teaching labs. The students perform screens with baits relevant to studies currently being performed in both the principal investigator's and the co-principal investigator's laboratories.