The Kellogg lab seeks to harness the power of transposases to engineer novel genome-editing tools. Recent development of CRISPR systems have revolutionized molecular genetics: This powerful gene-editing system can be directed to disable any target gene in a programmable fashion. However, CRISPR systems rely on introducing DNA double-strand breaks (DSBs), which has the potential to disrupt genomic integrity. Transposons, or “jumping genes,” are autonomous DNA elements that insert new sequences while bypassing DSBs. Recently discovered CRISPR-associated transposases represent a promising solution to insert new DNA sequences at desired chromosomal locations, since they are capable of programmed DNA transposition. However, these systems are not yet ready for genome-editing applications due to their low efficiency and off-site targeting. Furthermore, the mechanisms these systems use for recognizing and inserting DNA into their target-sites are largely mysterious. Using techniques in structural biology, genetics, and protein design, my lab will explore the mechanisms these CRISPR-associated transposases use to identify and integrate into their target-sites. Based on our mechanistic models, we will re-engineer these systems using computational protein design in order to develop new genome-editing tools that are adaptable, efficient, and precise. This work could produce a sophisticated tool for genome engineering or for gene therapies that could be used to treat a variety of human disorders.