Chalker Lab Profile

Research Focus: RNAi-directed genome rearrangement

Only a fraction of the genome is made up of actual genes. What functions are associated with non-genic DNA, and how do cells deal with “extra” DNA? All cells must recognize both coding and non-coding DNA and organize it for proper gene regulation. Recent discoveries have revealed that RNA molecules can dramatically influence the activity of the genome, guided by their sequence complementarity to specific regions. In the ciliate Tetrahymena thermophila, complementary, small RNAs direct massive remodeling of the developing somatic genome, a phenomenon mechanistically related to RNA interference (RNAi). These small RNA molecules target specific chromatin modifications to the homologous regions, and the DNA rearrangement machinery recognizes the modified chromatin state and eliminates the targeted DNA segment. Our lab aims to understand the regulation of this massive genome reorganization using a combination of genetic, molecular, and cellular biology approaches. These studies will certainly provide fundamental insight into RNAi-related mechanisms that direct chromatin modifications that are critical for transcriptional gene silencing and heterochromatin formation in eukaryotes. Underlying this work is a goal to understand how RNA molecules can communicate genetic information between the parental and developing genomes, which has great potential to reveal novel roles for RNA in epigenetic programming. Additionally, we believe many of the DNA segments targeted for elimination are important for germ line chromosome structure, and thus understanding how the cell specifically recognizes these sequences will contribute general knowledge of mechanisms ensuring chromosome stability that are essential to prevent aberrant rearrangements.