Grant: Foundation Grant

My work focuses on viruses that infect bacteria, called phages. Bacteria have developed "immune" systems to protect themselves from attack by phages. One of these systems is known as CRISPR-Cas and it is able to cleave phage genomes at specific spots, guided by an RNA sequence. In recent years, certain CRISPR-Cas systems, called Cas9, have been developed into technology that can be used to efficiently alter the human and other genomes. The advent of this technology has opened the possibility of curing human disease. My laboratory has discovered naturally occurring proteins that can potently inhibit CRISPR-Cas9 systems. These proteins will be used to improve CRISPR-Cas9 methods to make them safer for human therapeutic purposes. We will also investigate mechanisms and other uses for CRISPR systems. My laboratory also investigates structures that form parts of the phage particle itself. In particular, we work on phage tails, which bind to bacterial cell surfaces and inject the phage DNA into cells. Naturally occurring bacterial machineries, called tailocins, are closely related to phage tails and can be used to kill bacteria in a highly specific manner. We are developing methods to engineer these tailocins to kill any desired bacterial strain. These engineered tailocins will be used to manipulate the human microbiome to alleviate disease conditions, such as Crohn's Disease. Tailocins also have the potential to treat antibiotic-resistant bacterial infections.