Written by Andrew Hong, BS candidate, Colorado School of Mines and student in the 2024 Summer Research Program
During my summer in the Summer Research Program – RADIANCE track, I have had an amazing chance to work with Sean Tatum, PhD, in Professor Finck’s lab on the project, Branch Chain Amino Acids (BCAAs) and their effect on Type 2 diabetes.
While BCAAs are a part of normal diet, they are elevated in patients with type 2 diabetes and can predict future diabetes. Normally, the BCAAs are broken down into Branch Chain Keto Acids (BCKAs) which are again broken down again. A certain protein, BCKDH, is the enzyme for the breakdown of BCKAs. It can either be phosphorylated, meaning it is inhibited, or unphosphorylated, meaning the protein is active. In the average person, there is a normal balance of phosphorylated and unphosphorylated BCKDHs. In type 2 diabetics, there is a much higher proportion of phosphorylated BCKDH than unphosphorylated BCKDH. This leads to a buildup in BCAAs since they can no longer be broken down. In Dr. Finck’s lab, along with Dr. Tatum, we are investigating if increased phosphorylation of BCKDH leads to increased BCAAs and subsequent diabetes.
To further investigate and solve this issue, Sean Tatum and I have tested how BCKDH breaks down the food we eat such as fats, carbohydrates, and proteins, by challenging cells with these molecules. After transferring samples to a gel and running protein analysis, it is shown that fats increase the phosphorylation of BCKDH compared to untreated cells. This suggests that BCKDH activity is down and would lead to an increase in BCAA levels. In the future, we also plan to delete PPM1K, a protein that removes the phosphorylation from BCKDH to activate it. We hypothesize that this will lead to an increase in BCAAs and cause diabetes.
Through this experience, I have learned many new lab techniques such as performing protein analysis, genotyping, and cell culturing. I am grateful to have been taught the foundational skills of research as I move forward in my career where I aim study genetics using large data analysis and basic science techniques.