Elucidating the triggers of de novo initiation of epigenetic silencing in plants

除了基因，所有生物体的基因组都含有寄生虫，称为转座因子，如果不加以控制，它们会自私地使细胞发生突变。这个项目试图了解细胞用来“关闭”基因组寄生虫的最初步骤。新的分子工具将产生并交付给生物界，连同揭示“关闭开关”机制的新数据，使开关可以有针对性，避免，或用作研究工具。此外，该项目将通过指导和培训本科生、研究生和博士后水平的研究人员，为下一代生物学家加入未来的科学队伍做好准备。该项目还将使数百名STEM少数民族中学生接触科学研究和科学方法，以促进社区互动，并赋予STEM更多样化的未来。染色质修饰，如DNA甲基化，在基因组维持和表达中发挥重要作用，提供可遗传的表观遗传信息，在细胞世代之间传递。对于细胞来说，这种机制是谨慎的，因为它避免了每个细胞和每一代都需要从头确定（第一次）基因组的哪些区域应该表达或沉默。然而，这种机制使得研究人员很难确定控制染色质修饰模式如何启动的规则。这个项目的目标是确定这些规则。利用拟南芥作为模式生物，该研究包括开发新的分子工具来研究小RNA产生的初始触发，这是指导染色质修饰必不可少的一步。然后，新的工具将用于测试参与小RNA代谢的已知蛋白质是否可以触发从头沉默，并发现在触发点起作用的新蛋白质。这些工具应该在该领域具有广泛的实用性，并且该研究有望提供变革性的见解，以解锁靶向，避免或设计植物中染色质修饰的能力。该奖项由生物科学理事会的两个项目共同资助：分子和细胞生物科学部的遗传机制和综合有机系统部的植物基因组研究项目。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

In addition to genes, the genomes of all organisms contain parasites, called transposable elements, that can selfishly mutate the cell if not controlled. This project seeks to understand the very first steps that cells use to "turn off" genomic parasites. New molecular tools will be generated and delivered to the biological community, together with new data to reveal the "off-switch" mechanism, so that the switch can be targeted, avoided, or used as a research tool. In addition, the project will prepare the next generation of biologists to join the future scientific workforce by mentoring and training researchers at undergraduate, graduate and postdoctoral levels. The project will also expose hundreds of STEM-minority middle school students to research science and the scientific method to facilitate community interaction and empower a more diverse STEM future.Chromatin modifications, such as DNA methylation, play important roles in genome maintenance and expression by providing heritable epigenetic information that is transmitted across cellular generations. For cells, this mechanism is prudent, as it obviates the need for each cell and generation to determine de novo (for the first time) which regions of the genome should be expressed vs. silenced. However, this mechanism has made it difficult for researchers to determine the rules governing how patterns of chromatin modification are initiated. The goal of this project is to identify these rules. Using Arabidopsis thaliana as a model organism, the research includes developing new molecular tools to study the initial trigger of small RNA production, a step which is essential for directing chromatin modification. Then the new tools will be used to test whether known proteins involved in small RNA metabolism can trigger de novo silencing and to discover new proteins that function at the trigger point. The tools should have broad utility in the field, and the research is expected to deliver transformative insights to unlock the ability to target, avoid, or engineer de novo chromatin modification in plants.This award was co-funded by two programs in the Biological Sciences Directorate: Genetic Mechanisms in the Division of Molecular and Cellular Biosciences and Plant Genome Research Program in the Division of Integrative Organismal Systems.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.