My Internship
Overview
I worked with Dr. Chandler L. Walker in his Biomedical and Applied Sciences program in the IU School of Dentistry doing various laboratory procedures like cell culture, Western blot, and behavioral research with mice. His research is concerned with ALS (amyotrophic lateral sclerosis) and SCI (spinal cord injury). The main goal of Dr. Walker's research is to identify treatments for the fatal disease of ALS and understand the mechanism behind the degeneration that occurs in the body. He uses pharmacological, cell-based, and combination therapies to see if anatomical and neurological outcomes can be improved.
My Project
Why This Project is Important
ALS is a debilitating disease affecting the motor neurons of the body. After these motor neurons die, the ability of the brain to initiate and control muscle movement is diminished or even gone completely. When voluntary muscle action deteriorates, people may lose the ability to speak, eat, move and breathe; this presents significant problems for survival. The work we do matters because we are trying to identify the pathway(s) through which ALS works and what can be done to treat this debilitating disease.
Summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the development of progressive muscle paralysis. It is known that a protein important for cell growth and survival, Akt, stops the transcription of specific ligases involved in the degeneration of muscle cells. The reasons why Akt signaling is diminished in muscle tissue in ALS is not clear.
Carboxyl-terminal modulator protein (CTMP), which has been previously identified as a negative regulator of Akt, is a protein that is significantly elevated in atrophied muscle during the final stages of ALS.
Tumor Necrosis Factor-α (TNF-α) is an inflammatory molecule associated with muscle atrophy in ALS, and our previous research demonstrated that TNF-α stimulation of mouse muscle cells in cell culture increased CTMP expression. TNF-α also increases cellular nuclear factor kappa beta (NFkB) activity and nuclear localization.
In the present study, we hypothesized that TNF-α-mediated NFkB activation leads to increased CTMP expression. We tested this hypothesis by treating mouse muscle cells with TNF-α while prohibiting NFkB activity with a small molecule and examined CTMP expression with Western blot analysis.
We found that TNF-α significantly increased NFkB activity and nuclear localization in mouse muscle cells as well as increased CTMP expression, and that blocking NFkB activity in TNF-α treated cells reduced CTMP expression.
Acknowledgements
I worked with Dr. Walker, Christen Mumaw, Junmei Wang, and Pavani Kavuri during this internship. I want to thank all of these wonderful people for introducing me to the world of science and guiding me towards my future career path. I learned so much, from the basics of a laboratory to the more complex pathways on a cellular and molecular level. I was able to connect what I learned from my classes to this internship, and this allowed me to gain a new and personal understanding of classes that sometimes made little sense to me. Funding was provided by Neurodegenerative Disease Research, Inc.