NIH Director's Pioneer Award

概述：我正在提名自己获得美国国立卫生研究院院长S先锋奖，如果 获奖，我将用来研究基因的同源依赖的表观遗传机制 对动物模型以及最终对人类的监管。我研究的一个方面是 研究一种在植物中发现的与等位基因有关的现象，称为参数突变 导致基因表达的有丝分裂和减数分裂可遗传变化的通讯。 我的假设是，等位基因交流的范式转换机制，我们 发现了在植物染色质中的作用，也存在于哺乳动物中，可以解释 某些遗传性疾病的异常分离。 我把这篇文章组织成三个部分。在背景和意义上，我界定了 表观遗传学，简要总结了目前对机制的理解，并讨论了其 对了解一些人类疾病的重要性。在之前和现在的工作中，我 总结我们之前在参数调整方面的工作，并以此为基础来说明我的方法 为为什么这一提名应在NDPA过程中被考虑提供了证据。 在新的研究方向中，我简要描述了我提出的新方法，解释了如何 这篇文章建立在我过去工作的基础上，并讨论了为什么NDPA过程提供了一个独特的机会 来继续这项工作。

Overview: I am nominating myself for a NIH Director¿s Pioneer Award, which if awarded, I would use to investigate homology-dependent epigenetic mechanisms of gene regulation in animal models and eventually humans. One aspect of my research has been to study a phenomenon called paramutation, which was discovered in plants and involves allele communication that leads to a mitotically and meiotically heritable change in gene expression. My hypothesis is that the paradigm-shifting mechanisms of allele communication, which we have uncovered operating in plant chromatin, also exists in mammals and could explain the aberrant segregation of certain ¿genetic¿ diseases. I have organized this essay in 3 sections. In Background and Significance, I define epigenetics, briefly summarize the fields¿ current understanding of mechanisms and discuss its importance for understanding a number of human diseases. In Prior and Current Work, I summarize our prior work on paramutation, using this as a basis for illustrating my approach to science providing evidence for why this nomination should be considered in the NDPA process. In New Research Direction, I briefly describe the new approaches I am proposing, explain how this builds on my past work, and discuss why the NDPA process provides a unique opportunity to pursue this work.