Submitted by Jeremiah Fountain

Over the past 3 weeks, I have loved working in a lab at the BOG Regenerative Medicine Institute at Cedars-Sinai Medical Center. I am meeting so many great people and they are teaching me so much. I have sat in about 6 meetings and in there I think I learn the most about my research and others projects in the lab.

My first couple of weeks involved several hours of orientation and safety information. When I finally got into the lab my mentor Anjoscha Kaus taught me the basics about her project and what she does. She is focusing on Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. ALS damages the motor neurons (MNs) throughout the body. Upper MNs connect from the brain to the spinal cord and lower MNs from the spinal cord to the muscles through the body. The ability of the brain to initiate and control muscle movement is lost when the motor neurons die. Some people may lose the ability to speak, eat, move and breathe because of the loss of voluntary muscle movement that was affected.

The researchers here identified metabolic signatures in MNs they generated from C9orf72 ALS patient-derived induced pluripotent stem cells (iPSCs). The C9orf72 gene so far is the most frequently found gene connected to familial ALS. In their metabolic analysis the team here found a number of protein levels to be different, among those Ornithine Aminotransferase (OAT), an enzyme necessary for Proline synthesis, and Glycine Aminotransferase (GATM), critical for creatine synthesis. Both have been found to be dramatically increased in ALS samples, as showed by means of Protein detection through Western blotting evaluation. The 2 proteins closely intersect as GATM produces ornithine as a byproduct that is the essential substrate for OAT to synthesize Proline. This difference was accompanied by increased amounts of tRNA ligases, which are required for synthesis of RNA and proteins. Now we investigate in what CNS cell types the two candidates are expressed in ALS iPSC-derived motor neurons.

I am very eager to finish off the last couple of weeks as a research intern and travel to Berkley with my peers.