James J. Nagler, Ph.D.

Summary: My research interest is the development of gene drive technology in a vertebrate model system. Gene drives are currently being used in invertebrate animals (e.g., mosquito) that are vectors for human diseases, like malaria. Gene drives use genetic engineering to disable a gene critical to some important aspect of the organism’s biology that are inherited (i.e., passed on to subsequent generations). In the case of the mosquito, the gene drive makes the offspring sterile and reduces the population size. There are many possible applications for gene drives in vertebrates too, but most notable would be controlling human disease vectors. For example, bats are significant vectors of human disease. Gene drives could be used to make vertebrate disease vectors less (or non-) susceptible to function as a host for a specific pathogen. However, no gene drives have been employed to date in vertebrates for several reasons. There are many risks. One important aspect, yet to be tested, is the behavior of a gene drive at the population level. My lab is interested in testing a gene drive in a captive population of vertebrates (i.e., within the lab) over several generations.

Minimum classes: N/A

Projects: The project will begin the development of a gene drive in a small, freshwater fish, the turquoise killifish (Nothobranchius furzeri). Some of the many advantages of this fish model are that it has the shortest vertebrate lifespan (~ 2 months) and is easily propagated allowing many generations to be produced. Our intent is to exploit the killifish system to study population-level consequences of gene drives. The plan is to disable the tyrosinase gene which will lead to the highly observable phenotype of albinism. Tyrosinase catalyzes a key rate-limiting step leading to the formation of melanin in the skin and is highly conserved in fishes. A lab population exists at the University of Idaho that will be used for this research. A tyrosinase CRISPR-Cas9 construct will be microinjected into killifish eggs at the zygote stage. Embryos will be reared until melanin levels of skin pigmentation can be quantified. It is envisioned that the genetic engineering of the CRISPR-Cas9 construct, egg microinjection, fish husbandry, and melanin quantification will be the major components of the INBRE summer fellowship.