Topic: Gain-of-function mutations

SCN8A encodes a major voltage-gated sodium channel expressed in CNS and PNS neurons. Gain-of-function and loss-of-function mutations contribute to human disorders, most notably Developmental and Epileptic Encephalophy (DEE). More than 600 affected individuals have been reported, with the most common mechanism of de novo, gain-of-function mutations. We have developed constitutive and conditional models of gain- and loss- of function mutations in the mouse and characterized the effects of on neuronal firing and neurological phenotypes. Using CRE lines with cellular and developmental speci

Life of biological molecules spans time and length scales relevant at atomic to cellular time and length scales. Hence, novel molecular modeling approaches are required to be inherently multi-scale. Here we describe multiple methodologies developed in our laboratory: rapid discrete molecular dynamics simulation algorithm, protein design and structural refinement tools. Using these methodologies, we describe therapeutic strategies to combat this HIV and cancer, as well as design novel approaches for controlling proteins in living cells and organisms.