NIH Director's Pioneer Award
Principal Investigator: Vicki Chandler
Abstract: Overview: I am nominating myself for a NIH Director[unreadable]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 [unreadable]genetic[unreadable] diseases. I have organized this essay in 3 sections. In Background and Significance, I define epigenetics, briefly summarize the fields[unreadable] 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.
Funding Period: 2005-09-30 - 2010-07-31
more information: NIH RePORT
- Distinct size distribution of endogeneous siRNAs in maize: Evidence from deep sequencing in the mop1-1 mutantKan Nobuta
Department of Plant and Soil Sciences and Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USA
Proc Natl Acad Sci U S A 105:14958-63. 2008..The enrichment of miRNAs and loss of 24-nt heterochromatic siRNAs in mop1-1 should be advantageous for miRNA discovery as the maize genome becomes more fully sequenced...
- Paramutation in maize: RNA mediated trans-generational gene silencingMario Alberto Arteaga-Vazquez
BIO5 Institute, University of Arizona, Tucson, 85721, United States
Curr Opin Genet Dev 20:156-63. 2010..However, not all aspects of paramutation can be explained by known mechanisms of RNAi-mediated transcriptional silencing...