Analyzing the Activation State of Protein Bax

Author: Meghana Chithirala    Major: Chemistry/Biochemistry and Economics

Meghana Chithirala

My name is Meghana Chithirala. I am an honors college fellow at Fulbright College majoring in chemistry/biochemistry and economics and minoring in French. During the 2021 spring grant term, I worked with my honors mentor, Dr. Yuchun Du, and graduate research assistant, Brihget Sicairos-Meza, to identify cellular proteins that determine the activation state of the proapoptotic protein Bax.

This research is significant because Bax is one of the two key Bcl-2 family proteins (Bax and Bak) that function as an essential gateway to mitochondrion-dependent apoptosis and is involved in several major types of diseases such as neurodegenerative diseases and cancer. The mechanism of how Bax is kept in check in the inactive state in healthy cells and how Bax is activated during apoptosis remains unknown. The long-term goal of this project is to understand the molecular mechanism of Bax activation, an initiating and essential event in stress-activated apoptosis. My hypothesis is that one or more cellular proteins interact with Bax protein and keep Bax in the inactive state in healthy cells. Once this interacting protein(s) is stripped off under apoptotic conditions, Bax changes its conformation and migrates from the cytosol to mitochondria to induce apoptosis. The objective of this project is to use a novel proteomic approach to identify cellular proteins that determine the activation state of Bax. I am pursuing two specific aims: identifying cellular proteins that control the activation state of Bax in human cells using a proteomic method and verifying the interaction of identified proteins with Bax using Western blotting.

I found Dr. Du through the University of Arkansas website as I was looking through the faculty’s research interests. Dr. Du’s research activity interested me tremendously, so I reached out to him via email about becoming a part of his research team. My research topic is one he had already begun the research for and one I wanted to learn more about. Throughout my research journey, I have gained a great deal of first-hand experience in a laboratory. I work alongside Brihget mostly, and she has been a great instructor who explains everything very clearly and makes sure I know that it is normal to make mistakes while conducting research. I have been able to learn how to use equipment and practice lab techniques that I had learned about in my biology and chemistry lectures. Furthermore, it has furthered my passion for science and my goal to pursue a career in medicine. I have been able to develop critical thinking and collaboration skills, along with many others. The main challenge I have faced so far in my research is not being able to work in the lab as often as I would like to because of the necessary COVID-19 safety regulations. Therefore, I have not gotten as far in my specific research goals as I hoped, but circumstances should be more normal during the fall semester for me to fulfill all of my research aims.

Next year, I plan to complete my honors thesis and participate in a national conference and present my research. The Honors College Research Grant has given me the means to study this topic in an academic setting and pursue my future goals for research.