This is going to be a short and science-based entry. I’ll try my best to distill down the science to a level that (almost) everyone can comprehend!
When I applied to Emory for graduate studies, one of the school’s alluring features was its intensive commitment to research of neurodegenerative disease like Alzheimer’s or Parkinson’s. An entire floor full of professors’ offices and laboratories was dedicated specifically to the multi-pronged approach to understand these diseases better.
The term “neurodegeneration” refers to a multitude of conditions in which the patient suffers from continued loss of neurons (brain cells). Usually, our neurons stay put, even though they might make or break connections with other neurons. But in the case of a Parkinson’s patient, for example, the neurons are dying by the masses, leaving certain activities like walking and cognition very impaired.
I started my first laboratory rotation in the lab of Dr. Chad Hales, who is an expert on Alzheimer’s disease and frontotemporal dementia—basically, two important neurodegenerative ailments. We know that there is a certain pattern to Alzheimers. In cases of Alzheimer’s, there is an accumulation of this protein called A-beta, and when they clump together, they “stick” to each other and create major disruptions in the cell’s wellness. After the A-beta protein accumulates, another protein called tau joins the ride. Tau is a key component of the cell’s skeleton, and when too much tau and A-beta aggregate, brain cells start dying steadily.
So far, our model looks like this: A-beta accumulation —> tau accumulation —> pathology.
We have very limited knowledge of why and how the A-beta accumulation causes tau to clump together, too. We suspected that there might be other proteins involved in this cascade. Chad’s colleague and lab-neighbor is Dr. Nick Seyfried, who uses fancy techniques to determine which proteins have the highest probability of sticking together. The ultimate hope is to identify these vulnerable proteins and gather insights into the domino effect in order to provide better treatments.
My project with Chad was straightforward. I would use the data collected by Nick and formulate hypotheses about which proteins might aggregate in the brain and contribute to pathology. I used a method called immunohistochemistry to test my hypotheses. Immunohistochemistry is basically using chemical approaches and antibodies to label a specific protein within the cell— in this case, we were looking at cut-up post mortem human brains, and antibodies for four proteins that Chad and I agreed on. We found that none of the proteins we suspected was actually aggregating.
While it was a disappointment to have an experiment completely “fail", the experience taught me that an unsatisfactory observations usually lead to the greatest hypotheses. I’m no longer rotating in Chad’s lab, but I will definitely stop by once in awhile to catch up.