CURF: Becoming a Researcher in the Brodsky Lab

The University of Pittsburgh is well known for its vast array of research opportunities for undergrads across disciplines. From the start, I was extremely interested in pursuing research because it enhances problem-solving skills, allows you to gain hands on experience in your field, and challenge yourself. In one of the lectures for my Foundations of Biology II class, Professor O’Reilly taught us about alpha 1 antitrypsin deficiency. This disease is an example of how mutations in the sequence of DNA can result in a loss or gain of function in a protein. I was really interested in the research behind these findings, specifically in the relationship between protein misfolding and the molecular components that are associated with diseases. Therefore, Professor O’Reilly suggested that I reach out to Dr. Brodsky. Moreover, during that time, the pandemic had just started, and many news platforms were discussing that COVID had been developing new mutations. This furthered my interest in disease-associated genetic mutations.

Dr. Brodsky’s research focuses on understanding how misfolded proteins are recognized and destroyed in the cell and how defects in protein architecture can be corrected using drugs and genetic approaches. Therefore, I reached out to Dr. Brodsky and expressed my desire to learn more about his research and possibly become involved. Fortunately, after interviewing, I was given the opportunity to begin working in the lab. My first two semesters were spent being a lab aid before I was matched with my mentor, Morgan Kok, in the Summer of 2021. Morgan is a current graduate student in the Brodsky lab studying the KCC2 protein and the role it plays in regulating proper neuronal development in the brain. I found Morgan’s project extremely appealing because it allowed me to explore more about the relationship between the structure of a protein and the types of diseases and mutations that affect their complex structures. Currently, I am working on conducting stability assays on the 12 known disease-associated mutations found in KCC2. These mutations are linked to disorders such as schizophrenia, autism spectrum disorder, and epilepsy. From my preliminary data thus far, I have discovered that some of the predicted deleterious mutations are significantly less stable in the cell than wild-type KCC2. This is indicative of protein misfolding, which may be contributing to the pathogenesis of the diseases listed above. Therefore, protein misfolding is vital to study so we can understand how to treat people with specific mutations in KCC2. Overall, my work could potentially help millions of people that suffer from these diseases and provide insight into the complex cellular processes that cause them to occur. This directly aligns with my personal goals to contribute to science in a meaningful way.

Moreover, my project aligns with my professional goals to go into the medical field. Basic research will help me become a better physician because it will challenge me to find answers to things that are unknown. It will allow me to evaluate new evidence prior to making decisions and provide the best care to my patients. It is also important to establish valuable connections within the scientific community.

I would encourage all students that are interested in pursuing research to reach out to professors whose research aligns with their interests and goals. I am extremely grateful for the exposure and experience that I have gained from conducting research at the Brodsky lab. I also believe that working on a faculty-initiated research project gives one the opportunity to work closely with a mentor, such as a faculty member or another experienced researcher. This can help students gain new insights and perspectives on their projects. However, I recommend that students first start off by reading about the work that a lab focuses on by examining published papers and background information. This will then demonstrate their enthusiasm.

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