Spotlight: Unlocking the Secrets of Lou Gehrig’s Disease

Should I be an engineer? Should I be a medical doctor? Early in his academic career, Keith Nylin considered both these professions. Then, he discovered biochemical research. His love of problem solving and medical interests were perfect for this type of work, and he quickly became interested in the work of Dr. Joe Beckman, an EHS Center Investigator investigating the causes of ALS (Lou Gehrig’s Disease).

As a graduate student in the Department of Biochemistry and Biophysics, Nylin currently spends his time trying to figure out the subtleties of an enzyme called superoxide dismutase (SOD). SOD is a protective enzyme that helps prevents oxidative damage to cells including spinal cord motor neurons. When SOD functions in an improper way, motor neurons are damaged, thus leading to the debilitating and eventually fatal effects of ALS.

Enzymes are proteins. Proteins are made up of building blocks called amino acids. When the wrong amino acid is used during the construction of a protein, the protein functions improperly, usually because the shape of the protein is altered, sometimes dramatically, sometimes very subtly. These improper amino acid substitutions are called mutations. ALS is caused by more than 120 different mutations, all occurring within the SOD enzyme. The structural changes appear to cause the removal of a zinc atom normally stuck to the SOD enzyme. This loss of zinc causes the protein to malfunction and become toxic to motor neurons.

How does one study the impacts of a protein mutation? Traditional studies involve several processing steps once the tissue has been collected to separate the proteins from other materials in the sample. These processing steps can cause artificial changes in the protein sample, which mask the real effect of a mutation. In the research of subtle protein structure changes, it is difficult to tell the difference between a processing artifact and the real change caused by the protein mutation.

Recently, Nylin, with the assistance of the research associates in the EHS Center Mass Spectrometry Facility, has developed a surprisingly simple method that involves using a very tiny sample of spinal cord tissue from animals afflicted with ALS. With very minimal processing, he is able to inject the tissue sample directly into sensitive analytical instruments. Previously, no other analytical method has demonstrated this effectiveness or the simplicity of injecting a tissue sample directly into an instrument. With this new method, Nylin has been able to unlock several new doors to the ALS mystery. Additionally, the method holds promise for the study of other diseases caused by protein mutations.

Analyzing Wastewater

Tracking Air Pollution

Finding Signs of Aging

Cancer Prevention

Understanding Skin

Nanotech's Gatekeeper

Bridging the Gap