Department of Biology

Joshua Meisel

Assistant Professor of Biology
Ting Tsung and Wei Fong Chao Endowed Chair in Neuroscience

Research Description

Mitochondrial genetics and metabolism in health and neurodegenerative disease

Mitochondria are the products of an ancient symbiosis wherein an archaeal cell engulfed a bacterium, giving rise to the “powerhouse” of the eukaryotic cell. Mutations in mitochondrial genes – encoded by both the nuclear and mitochondrial genomes – underlie common and rare neurodegenerative diseases for which we have no effective therapies. Our lab’s goal is to discover genetic and environmental suppressors of mitochondrial dysfunction to ultimately rescue mitochondrial disease.

My work has explored how hypoxia (low oxygen) can rescue multiple models of mitochondrial disease (e.g. Friedreich’s ataxia and Leigh Syndrome). Using forward genetic screens, we identified suppressor mutations that also rescue these mitochondrial defects, shedding light on the hypoxia rescue mechanism and identifying new genetic pathways with therapeutic potential. My lab at Brandeis will use C. elegans genetics, neurobiology, and biochemistry to investigate the mechanisms that govern mitochondrial adaptations to (1) variable metabolic demands across tissues and cell types, with a particular focus on the dopaminergic neurons, (2) mitochondrial dysfunction which occurs in rare disease or naturally as part of the aging process, and (3) changes in the environment, such as oxygen gradients experienced during development or in natural environments.