Kellogg lab @ Cornell

the next generation of genome-editing

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 while bypassing DSBs, 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.