Research in the Carrington lab focuses on RNA-mediated regulation and silencing of genomes, genes and viruses. This lab focuses on the biogenesis, functions, and evolution of small RNA-directed silencing pathways in multicellular eukaryotes.
Small RNA-based silencing serves a regulatory mechanism during growth and development and in response to stress. It also functions as a transposon and repeat silencing mechanism, and as an antiviral response in plants and some animals. The Carrington lab uses a combination of genetics, genomics, computation and other approaches to address fundamental mechanistic problems using model systems, such as Arabidopsis thaliana and Brachypodium distachyon, but it also seeks to develop tools and approaches that have practical relevance. This lab is committed to the development of quantitative methods for mapping and quantifying high-throughput sequencing (HTS)-derived small RNA data, and to making these data available to the public through accessible, useful databases.
Diversification and evolution of silencing pathways.
HTS studies in a variety of plants and other organisms have revealed the diversity of ancient and recently evolved miRNA genes, and vast arrays of siRNAs from long dsRNA. The systematic analysis of mutants with defects in miRNA and siRNA function revealed several distinct biogenesis pathways for each class, and target RNAs that are regulated by small RNA families. Distinct small RNA biogenesis and effector components are involved in transcriptional and posttranscriptional silencing systems in plants. We have explored biogenesis, effector and specificity mechanisms of miRNA, trans-acting siRNA (tasiRNA), antiviral siRNA, and other small RNA classes using Arabidopsis thaliana.
Functional specialization of Argonautes and amplification of silencing signals.
The Carrington lab is particularly interested in the effector proteins - Argonautes (AGOs) - through which small RNAs function, and mechanisms of silencing amplification through RNA-dependent RNA polymerases. Plants have expanded sets of AGO genes that encode functionally diverse proteins. In addition to using HTS platforms to identify, characterize and quantify classes of small RNAs, the lab has profiled small RNAs that are affected by biotic stress, that associate with distinct Argonaute proteins, and that are associated with various growth and development phenotypes. The lab also explores the nature of small RNA regulatory networks, including small RNA that move between cells and AGO-small RNA-target interactions.