Grant: Project Grant

Patterns of gene expression distinguish different cell types (i.e. brain, hair, and muscle cells express different sets of genes to make them different from each other). Misregulated gene expression can lead to developmental disorders, infertility, cancer, and other diseases, thus there are many cellular safety mechanisms that regulate the process. One key mechanism for controlling gene expression involves sRNA pathways that can act in different cellular compartments and at several steps in the process of turning a gene on or off. Small RNA pathways play key gene regulatory roles in a variety of organisms, and rely on conserved Argonaute effector proteins, which utilize sRNAs to provide sequence-specific identification of target genes. Our research focuses on understanding how sRNA pathways regulate gene expression in the nuclei of cells known as germ cells (sperm and egg). The nucleus is where the process of gene expression initiates, and sRNA activities in the nucleus are currently poorly understood, especially in animals. Our studies focus on understanding the molecular mechanisms by which sRNA pathways impact chromatin (how chromosomes are packaged), using the nematode, C. elegans, as a powerful model system, and applying integrated genetic, genomic, molecular and cell biology approaches. Uncovering the molecular mechanisms of sRNA-mediated gene regulation in germ cell nuclei reveals a deeper understanding of basic cellular functions that contribute to development, differentiation, fertility and disease, and provides a more precise means to manipulate gene expression, leading to more effective sRNA-based therapeutics and laboratory techniques.