Genetic Modifiers of Neurodegenerative Disease
Using chemically induced and transgenic C. elegans models, we examine how genetic background modifies neurodegeneration-associated behavioral and neuronal phenotypes.
Neurodegenerative diseases, including Parkinson’s disease and tauopathies, display considerable variation in severity and progression among individuals. Although some disease-associated genes and environmental risk factors are well established, the full spectrum of modifying alleles and the molecular mechanisms underlying their effects on disease susceptibility is not known.
We are investigating how natural genetic variation modifies neurodegeneration-associated phenotypes using two complementary C. elegans models: a chemically induced model of Parkinson’s disease-related dopaminergic dysfunction and a transgenic model expressing mutant human tau protein.
A central component of this work is the development of automated behavioral phenotyping approaches that allow reproducible comparisons across genetically diverse strains. By introducing disease-associated exposures or transgenes into different natural genetic backgrounds, we aim to identify strains that exhibit relatively resistant or susceptible phenotypes. We then use fluorescence microscopy to examine whether these behavioral differences correspond to changes in neuronal structure.