Grant: Project Grant

The major challenge in human genetics is to use the information on gene variants to help clinical practice. To help address this issue, I have pioneered zebrafish models of genetic disorders of the brain. For example, we developed the first in vivo models of genes in amyotrophic lateral sclerosis (ALS), which led to our discovery of a repurposed drug showing promise in clinical trial. I now seek to develop new models of brain diseases in order to better understand and eventually treat neurological disorders. We have three specific aims. We will characterize new zebrafish models of genes with mutations causing both ALS and a form of dementia by discovering novel protein interactors and studying their synaptic biology and pathobiology; we will also study motoneurons derived from ALS patients and transplanted into chimeric zebrafish embryos to test different drug combinations to treat sporadic ALS.