Grant Shelnut

Author: Grant Shelnut | Major: Biology | Semester: Spring 2023

Grant Shelnut is an alumnus of the J. William Fulbright College of Arts and Sciences. He majored in Biology and completed biological research under the direction of Dr. Daniel Lessner. He finished up this research and defended his honors thesis this Spring of 2023. Now that he has graduated from the University of Arkansas, he is set to begin medical school at the University of Arkansas for Medical Sciences in August.

My path to getting involved in undergraduate research began during my junior year in Dr. Paré’s Genetic Engineering class. As a future medical doctor, I found the utility of genome manipulating techniques to be intriguing and surprising. While I knew that these techniques were being applied at some level in the medical field, upon learning the molecular details, I quickly began to realize how advantageous their uses can be. In fact, I believe that, as an endocrinologist explained to my mother, “genetics is the future of medicine.” I thus was hopeful to gain undergraduate research experience with what is one of the most well-known gene editing tools, CRISPR-Cas9.

I was very much challenged by the research process from the jump. The COVID-19 pandemic made it difficult for me to be accepted into a lab for about a year. Moreover, I am naturally introverted and have oftentimes struggled asking others, especially those in authoritative positions, for help and guidance. My drive to complete research that utilized genetic tools at the undergraduate level helped me to overcome this struggle; I realize now that I cannot let my natural tendencies, some of which can be irrational, be a roadblock to the fulfillment of my goals. Thankfully, Dr. Daniel Lessner, who was my professor for Prokaryote Biology, gave me an invaluable opportunity to use a CRISPR-Cas9 system as an undergraduate.

Specifically, my project employed a CRISPR interference system to repress the expression of hdr genes that encode for a heterodisulfide reductase in the archaeon Methanosarcina acetivorans. This enzyme was hypothesized to be essential to the process of dinitrogen fixation in M. acetivorans, as it was proposed to facilitate electron delivery to allow the process of nitrogen fixation to occur. Therefore, repressing hdr and thus reducing the amount of heterodisulfide reductase being produced in M. acetivorans allowed for analysis of the enzyme’s proposed essential role in nitrogen fixation (it was not supported to be essential by the project’s findings). Better understanding of nitrogen fixation and all of its components may one day allow for implementation of the process into organisms that rely wholly on the uptake of already fixed nitrogen from the environment. Plants, for example, are included in this; therefore, we have to provide them with polluting, expensive, and limiting fixed nitrogen-containing fertilizers. Implementing a dinitrogen-fixing process into plants would reduce the use of fertilizers and eliminate many of the problems associated with said use. Still speaking practically about the project, better understanding of electron flux in M. acetivorans could eventually lead to advantageous production of a biofuel within the organism. Throughout my project, due to these practical implications and the complexities of the tools I was using, Dr. Lessner stressed to me that my work was not merely a simplistic, non-important experiment that he haphazardly assigned me due to my status as an undergraduate. He assured me that my findings could have important consequences, and I truly felt this to be the case from start to finish. Furthermore, as a non-expert in a lab full of experts regarding M. acetivorans and microbiology in general, I never felt belittled. Instead, I felt enriched and supported by members of the Lessner Lab. Dr. Lessner was readily available to look over my writings and have conversations about my confusions. Jasleen Saini, the graduate student that led me through the day-to-day lab protocols, was one of the most helpful individuals I’ve ever worked with. She was patient with me even through a constant inundation of questions. My honors thesis committee, which included Dr. Lessner and Dr. Paré along with Drs. Susanne Striegler and Matt Clay, challenged me to be able to communicate my findings to a panel of professionals. This will help me to be more comfortable in future research presentations.

I am very grateful for my time in the Lessner Lab and for the Honors College at the University of Arkansas for helping to fund my experience. I was fortunate to participate in important research whilst establishing a strong foundation for my future research endeavors and my medical career. A key principle that I will apply to future research is to constantly shift my lens back and forth from the overall purpose of a study to the day-to-day, experimental protocols. I did not efficiently zoom my lens in and out, so I sometimes found myself lost. I now know how critical it is to constantly pay close attention to both the big picture and the details.

Genetics is the future of medicine, and I hope to be a part of that future. Thanks to the Lessner Lab and the University of Arkansas, I have the confidence that I will be able to make a difference.