In the Kadonaga lab, I will explore the role that structures called “prenucleosomes” play in regulating gene activity. To produce a compact chromosome, long strands of DNA are wound tightly around spools of proteins. These protein-DNA bundles form the nucleosome, a particle that controls access to the underlying genes. The regulatory regions of active genes tend to lack nucleosomes—and instead appear to harbor prenucleosome-like structures that include shorter lengths of DNA that are less tightly coiled. By using an array of cutting-edge tools in biochemistry, molecular genetics, and genomics, I will investigate the formation and function of prenucleosomes in cells. I will identify proteins that selectively interact with prenucleosomes and assess whether they can convert nucleosomes into prenucleosomes—an action that could help activate genes. I will also map the prenucleosomes in embryonic stem cells and determine whether their location corresponds with genes that are switched on as the cells specialize. Findings from this work should lead to new insights into how gene activity is controlled and could provide new approaches for gene therapies and treatment of human diseases.