Molecular Architectures

Science Research Initiative


Development of Unexplored Molecular Architectures

Dr. Ryan Stolley – Research Assistant Professor, Department of Chemistry

 

Dr. Ryan Stolley

As complicated as chemistry can be, really everything is constructed like LEGOs – pieces with limited sizes, shapes, geometries all come together to make the intricate and complex. Because of this, if you look around you, unless it grew from the ground, nearly everything you see has been designed from the atom up. Over the span of human history, we have built an understanding of the matter that comprises our universe and have become quite adept of combining the 100-odd elements into the materials of modern society. Specifically, in organic chemistry – the chemistry of life – we have even less available atoms and possible connections; and given the importance to our existence this field has a very strong grasp on the possible.

So, it is incredible to conceive that in the limited space of atomic composition and connectivity in organic chemistry, a group of relatively simple, diverse, and powerful group of atoms has eluded investigation. Research into frequently observed group of atoms, called functional groups, has a rich history and students in our lab will have the opportunity to expand on lessons of the past - applying classical reaction development techniques - and deriving new paradigms as we investigate this sandbox of fun new pieces of the universe

Our SRI stream will uncover new chemical reactions to build never before seen arrangements of atoms and use a variety of chemical, analytical and computational tools to uncover how these new groups of atoms behave; and to expand on this capability to build ever more complex molecules. In our lab students will learn the principles of organic chemistry and chemical experimentation and the instrumental tools for us to ascertain structure and function of organic molecules.

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James Detling, PhD’69

James K. Detling

 

 

James K. Detling (PhD’69) arrived at the University of Utah from Ohio State University where he had just finished his Master’s degree in botany. He followed his graduate advisor, Dr. Lionel Klikoff, who transferred to the U as a tenure-line faculty member. While his advisor guided Detling’s research and mentored him in the ways of becoming a university faculty member, “perhaps my fondest memories are of Dr. Kimball Harper,” he says. Detling’s PhD research involved a study of physiological ecology of saline-tolerant halophytes in the salt deserts west of Salt Lake City. Of Harper, Detling says, “He always graciously shared his vast knowledge of the ecology of Utah’s various ecosystems, and made himself available to answer questions or discuss ideas. Imagine my disappointment,” he says somewhat cheekily, when several years later he learned that Harper had left the U to join the faculty at the Ute’s traditional rival located south of Salt Lake City: Brigham Young University.

In Utah, Detling enjoyed exploring the mountains and deserts, “first to scout out potential field sites for my research in plant ecology,” he says “and then to explore the fabulous outdoor recreational opportunities they provided.” After teaching at the U for one year as a replacement for Harper who went on sabbatical, he taught at a private liberal arts college in Ohio for five years. Following that, in 1975, he returned to the west, to Colorado State University where he remained on the faculty until his retirement in 2010.

In Fort Collins his professional activities included the study of biotic and abiotic factors affecting both structure and function of grassland ecosystems. On the editorial board of the journal Frontiers in Ecology and the Environment, the Berkeley California native was also elected Fellow of The American Association for the Advancement of Science. Additionally, he was also designated an ISI Highly cited researcher.

In the 80s Detling retreated to the field of the mixed-grass prairie at Wind Cave National Park in South Dakota. There he studied and reported on how black-tailed prairie dogs create habitat patches characterized by altered species composition, lower standing crops of plants, but also higher forage quality. “Native wildlife species such as bison, pronghorn, and elk preferentially feed on these prairie dog colonies and likely derive nutritional benefits from doing so,” he reported. Findings supported his hypothesis that genetically-based morphological and physiological differentiation had occurred in several native grass species as a result of strong selection pressures from grazing mammals on prairie dog colonies.

A decade later he turned his attention to “Grassland Vegetation Changes and Nocturnal Global Warming,” resulting in a  paper of the same title co-authored by Richard D. Alward and Daniel G. Michunas published in Science.

Since retirement Detling has continued research on grassland ecology with former students and colleagues. He has also turned from the study of one kind of grassland to another--the golf course—which has come in handy since the advent of the coronavirus pandemic has curtailed other beloved activities: traveling and dining out.

 
by David Pace
 

Sonia Sehgal

Sonia Sehgal

 

U Biology's Sonja Sehgal accepted a Beckman Scholarship this past spring to add to the trove of awards that were already sitting on her academic “mantle” at home. Collective kudos include a Biology Research Scholars Award, a College of Science Scholarship and a Utah Flagship Scholarship.

The Beckman, however, is a step up from her other awards. It represents an unprecedented opportunity, perhaps found nowhere else, in which an undergraduate researcher can hone her craft at the bench and under extraordinary mentorship. The program is a 15-month, mentored research experience for exceptional undergraduate students in chemical and biological sciences, and Martin Horvath, associate professor in the School of Biological Sciences, will serve as her mentor. (Rory Weeks, undergraduate in the Department of Chemistry is the second U Beckman Scholar for 2020-21.) Each scholar receives a $21,000 research stipend to facilitate nine academic calendar months and two three-month summers of research experience. Recipients from around the nation participate in the prestigious Beckman Symposium each summer with one another. Their research began in June 2020 and will conclude in August 2021.

“I started out as a freshman in the ACCESS,” the biology senior explains, referring to the decades-long program hosted by the College of Science Program for Women in Math and Science. “Through this program, I was able to explore various fields in STEM which really kick-started my interest in pursuing biology! Joining the Horvath Lab further sparked my curiosity and has shown me that science goes beyond the stereotypical image of a “scientist.”

Tracking toward a career in medicine

Sonia Sehgal (undergraduate, Biology Research Scholar, Beckman Research Scholar) and Martin Horvath discuss the structure of MutY

Sonia Sehgal (undergraduate, Biology Research Scholar, Beckman Research Scholar) and Martin Horvath discuss the structure of MutY.

Sehgal is far from stereotypical, as a scientist or as an undergraduate. As a woman she knows that she’s in the minority as she works through her academic career and finally a professional career in STEM (Science Technology Engineering and Mathematics). As a complement to her academic career, the Sandy, Utah native has found a job as a University Ambassador. “The ambassadors work closely with the Office of Admissions to share our experience and bring a personal perspective to prospective U of U students,” she says. “When not giving tours or working recruitment events, we can be found having a good time with each other or,” she quips, “practicing walking backwards.”

Though Sehgal finds herself walking backwards while giving tours, she is definitely moving forward in her academic career. “I’m excited to continue doing research and I also plan on attending medical school after graduation. I want to learn about the various mechanisms that can cause diseases to present themselves in different forms across individuals. I want to use this platform to relay these findings with patients and create more representation in the field to strive for a more trusting and effective patient interaction.”

But before medical school, there’s research to be done, a focus in undergraduate education in the SBS that has arguably become the School’s signature.  “In the Horvath lab,” Sehgal explains about her work, MUTYH is a DNA repair enzyme commonly related to diseases like cancer. I am currently finding the role of different biological probes to see how they can affect the activity of this enzyme. Learning more about regulating the activity of MUTYH will allow us to create better drug-targeting systems for cancer in the future.” What most people, even the scientifically-inclined, may not know about the model subject Sehgal is studying is that the MutY enzyme can be found in almost every living organism, yet there is still a lot we don’t know about it.

Hangin' out.

That’s something that inspires rather than discourages Sehgal who will graduate with her BS in 2021. With the help of the Beckman Scholarship, the mentorship of Horvath and the broad view of higher education she gets by being an ambassador, Sehgal finds her future as she tracks toward a career in medicine, promising. And true of all of accomplished undergraduate researchers of Sehgal’s stripe, she is poised for far more awards, and accomplishments.

“The Beckman experience has been going well,” she reports. “Because of the COVID-19 pandemic, the first stage has been virtual. I have been working on coding and molecular docking. However, I look forward to getting into the lab next semester and start testing!” Of Sehgal Horvath adds, "Sonia has a gift for finding a simple clear question to address in her science. She will go far. I feel really lucky to have had the chance to work with her these past years."

Asked what her interests and “likes” she doesn’t stray very far from her time in the lab. She likes rock climbing, dogs … and getting positive results for polymerase chain reaction (PCR), a method widely used to rapidly make millions to billions of copies of a specific DNA sample.

It’s the sort of thrill that allows a budding scientist, like Sonia Sehgal, to take a very small sample of DNA and amplify it to a large enough amount to study in detail.

Beckman Abstract

  • "Finding the role of biological probes on MUTYH activity,"(S. Sehgal)
    DNA damage is implicated in many cancers, such as colorectal cancer. One form of this damage occurs when guanine becomes oxidized to form 8-oxoguanine (OG). MUTYH is a base excision repair (BER) enzyme in humans that excises adenine (A) at OG:A lesions in DNA and thus prevents mutations that may arise after rounds of replication. Interestingly, both inhibition and overactivation of MUTYH can contribute to cancer-causing activity. In this project, MUTYH will be studied through computational modeling and an activity assay to find biological probes that can bind to the protein and affect its function. These probes can later be tested in animal models and may serve as the foundation for anticancer drug discovery. In addition, through analyzing the effect of biological probes on this enzyme, the BER pathway and the dual role of MUTYH in preventing and causing cancer can be further understood. Use of these probes to control MUTYH activity and BER overall can aid with creating more efficient drug targeting systems for cancer treatment in the future.

 

 

by David Pace