Kevin Wilson

I am currently an associate professor of biochemistry and adjunct professor of microbiology at Oklahoma State University. As one of Oklahoma's three major universities, OSU is located in the pleasant town of Stillwater, near the geographic center of America. Here, I teach biochemistry to large classes of undergraduate students. I also lead a vigorous research program on antibiotics and bacterial translation mechanisms. Finally, I help to advise students through their course curricula and research toward their bachelor and doctoral degrees at OSU, and their career choices beyond that. I am challenged by all three jobs. I am thrilled to be surrounded by enthusiastic and congenial students, professors, and administrators, who are proud to call OSU "America's brightest orange".

How I ended up at OSU involved a long and circuitous journey, which I will tell briefly. I grew up in south Florida, near swampland of the Everglades. As a young boy in the 1970s, I became passionately interested in swamp life, particularly birds, and I envisioned becoming an ornithologist as an adult. As I grew older, my interests shifted toward biochemistry because I wanted to understand the molecular foundations of all life forms. An outstanding chemistry teacher, Helen Reynolds, sparked my interest in biochemistry when I was a student at Jupiter High School.

In 1984, I began my undergraduate studies at the University of Florida. Since they did not offer a bachelor degree in biochemistry, I transferred to the University of Arizona. In my senior year, I became excited by genetic engineering technologies that were being developed in bacterial cells – harmless lab strains of Escherichia coli. My first research project, under the direction of Professor John Little, focused on gene expression in E. coli viruses. I took advantage of new techniques for engineering DNA molecules, the polymerase chain reaction (PCR) and site-directed mutagenesis (Mullis & Smith, 1993), which later proved valuable in my doctoral research. This experience convinced me to continue research on the Central Dogma of gene expression: DNA Replication -> Transcription -> Translation.

In 1988, I moved to the University of Oregon to pursue graduate studies under the direction of Professor Peter von Hippel. He is a pioneer of biophysical chemistry, especially protein enzymes that catalyze DNA replication and transcription. My doctoral research focused on transcription catalyzed by the central enzyme RNA polymerase purified from E. coli. I examined the formation of hairpin structures in the RNA synthesized by the polymerase, and analyzed the effects of RNA hairpins on the thermodynamic stability of transcription complexes.

During my graduate studies, I became excited by the discovery of ribozymes (enzymes composed of RNA). Their discovery solved a major conundrum: How could nucleic acids serve as both hereditary material and catalysts in the first living cells on Earth? In modern cells, the most sophisticated ribozyme is the ribosome, whose ribosomal RNA molecules catalyze the translation step of gene expression. Many modern viruses carry RNA hereditary material, such as those causing AIDS or flu in humans.

After earning my Ph.D. in 1995, I decided to continue research along the pathway of the Central Dogma, and study the biochemistry of translation in E coli. I moved to the University of California at Santa Cruz, where I conducted postdoctoral research under the direction of Professor Harry Noller. He is one of the most prominent scientists studying ribosomes and one of the first to propose that the ribosomal RNA catalyzes the formation of peptide bonds between amino acids during the synthesis of proteins in the process of translation. My postdoctoral work lead us to groundbreaking insights into how translation is regulated by unusual proteins that mimic the shape transfer RNAs, which carry amino acids to the ribosome during translation. While this work was in progress, I was extraordinarily fortunate to witness truly groundbreaking research that led to atomic structures of the ribosome for the first time. The first crystal structure of a fully assembled bacterial ribosome was determined by my postdoctoral colleagues in Noller's lab. Along with atomic structures of the ribosome's subunits determined in three independent labs, this work revolutionized our understanding of translation and was eventually recognized by a Nobel prize in 2009.

I landed my first appointment as an assistant professor at the University of Alberta in Western Canada. I remember bravely moving to the Cold White North in January 2001. My first winter was a harsh adjustment in more ways than one. I experienced temperatures of -40 (same number, Celsius or Fahrenheit scales!) for the first time in my life. I found a stark beauty in seeing the Northern Lights above the city of Edmonton, as well as the rugged Canadian Rockies. While adjusting to life in Canada, I also faced the challenge of building my independent research lab.

My continued research on bacterial ribosomes offered many exciting avenues, but changed my perspective, in light of the ribosome structures. Since my lab was in a medical school and I needed grant money, my research progressively shifted toward antibiotics, which commonly target ribosomes in pathogenic bacteria. This shift was greatly facilitated through my collaboration with Professor Diane Taylor, along with help of graduate and postdoctoral students in my lab. My connections with other professors in the international RNA Society, as well as RiboWest and RiboClub of Canada, would later prove valuable to me.

We had a productive lab and published several notable research papers over the next several years. We deciphered the mechanisms of GTP hydrolytic proteins and antibiotics that regulate translation. However, because my position required me to procure my external salary, I faced unexpected financial difficulties by 2010. Fortunately, after graduating my students, I was able to move to McGill University in Montreal, where I spent a sabbatical year in Professor Nahum Sonenberg's lab. During that year, I was strategically planning to land a permanent position, preferably in Montreal, but also searched widely across North America.

As many of my academic colleagues know, our profession can often be unpredictable. So for me in 2011, I was invited to interview at OSU and offered the position that I currently hold. I had not been to Oklahoma before that time, and I was pleasantly surprised by what I found here. Although Oklahoma's weather is unpredictable and inhospitable at times, the wonderful people of this university make this a great place to be. We have a vibrant community of professors and students in our department. It is a wonderful time to be at OSU!

Research Interests:

Antibiotics are some of our most powerful and valued drugs, virtually eradicating previously dreaded diseases such as scarlet fever, tuberculosis, and bubonic plague. Ironically, only a few new antibiotics have been introduced since the 1960s. A crisis looms on the horizon with old antibiotics losing their effectiveness due to the rise of multidrug-resistant bacteria, chronic infections, and immune-compromised patients. Resistance arises from two primary sources: from bacteria harboring mobile resistance genes that can be spread to other cells; and from 'persister cells', which are dormant variants of regular bacteria that are highly tolerant to antibiotics. The rise in resistance is exacerbated by our ubiquitous use of antibiotics in everything from medicine to agriculture. Furthermore, antibiotics indiscriminately attack harmful and helpful bacteria in our gastrointestinal tracts and societies.

Antibiotics from natural sources (plants, fungi, and other bacteria) commonly target bacterial ribosomes, which translate mRNAs into proteins. This translational machinery is also a source for acquiring resistance to antibiotics. The highly conserved nature of this machinery facilitates our broad use of antibiotics, yet it also promotes resistance in bacterial populations. Translation and antibiotics are inextricably connected to bacterial physiology, growth and multiplication. Yet there is a significant lack of information about how ribosome-targeting antibiotics alter bacterial physiology.

To begin to fill this void, my lab is investigating how antibiotics perturb the translational machinery in bacterial cells. Using novel methodology, we are purifying the full translational machinery from both harmful and helpful bacteria. We are quantitatively assessing the components of this machinery and other putative factors connecting it to bacterial physiology. We are comparing the effects of antibiotics on the composition and dynamics of the translational machinery. These studies will reveal how antibiotics that target the ribosome dismantle bacterial physiology, leading to bacterial death. These insights will be a critical prerequisite for the development of new more effective and specific antibiotics. And they prepare us for the new more deadly drug-resistant bacteria that will most assuredly arise in the future.