Our goal is to understand the molecular mechanisms of motor neuron disease.

The list of genes associated with diseases of the motor neuron is long and growing rapidly:

Hereditary Motor Syndromes
http://neuromuscular.wustl.edu/synmot.html

Inherited Peripheral Neuropathies Mutation Database
http://www.molgen.ua.ac.be/CMTMutations/Home/IPN.cfm

• What are the biochemical and biophysical functional consequences of mutations in genes that result in motor neuron disease?
• What role do these proteins normally have in a healthy motor neuron?
• At a molecular level, how do motor neuron disease gene products interact with one another in the cell?
• What is the basis of motor neuron selectivity in these syndromes?

The Kolb Lab studies the functional consequences of mutations that cause distal hereditary motor neuropathies, spinal muscular atrophies and amyotrophic lateral scperosis using biochemical and biophysical techniques. One current project in the lab centers upon the small heat shock protein family. These proteins normally function as protein chaperones and are involved in the cell stress response, however mutations in some of these proteins result in hereditary motor neuropathy. Our studies of heat shock proteins include the study of protein-protein and protein-RNA interactions, cellular models of cell stress and protein chaperone activity. Moreover, the Kolb Lab is physically located within the Molecular & Cellular Biochemistry Department which has strengths in structural biology affording the opportunity for detailed studies of heat shock protein interactions.

A second area of study focuses upon RNA processing defects in motor neuron disease.  Influenced by the central role of the survival of motor neurons gene in ribonuclearprotein assembly, we seek to understand how disruption of RNA processing can lead to a motor neuron specific phenotype. The Ohio State University offers a uniquely large concentration of RNA biologists. RNA Group and Kolb Lab members are active participants. This affiliation offers unique opportunities to form collaborative efforts to explore RNA metabolism and processing in motor neurons.