Newswise — The Howard Hughes Medical Institute has awarded International Student Research Fellowships to three University of Chicago graduate students in the physical sciences, an unprecedented number for the division. The recipients are Di Liu and Boxuan Zhao in chemistry, and Monika Scholz in the biophysical sciences, a joint program of the Biological Sciences Division and the Physical Sciences Division.

The prestigious fellowship, which provides $43,000 annually for up to three years, is awarded to international PhD students in the biomedical and physical sciences who may not be eligible for fellowships or grants through U.S. federal agencies.

Di Liu, researches the topology (knots or links, loosely speaking) of nucleic acids and their biomedical applications in the research group of Yossi Weizmann, assistant professor in chemistry. Liu earned his bachelor’s degree in chemistry from Nanjing University, graduating in 2011 at the top of his class. As an undergraduate in Zijian Guo's group, Liu researched the development of light-activated platinum-based anti-cancer drugs.

Unlike tying a shoelace, Liu explains, creating molecular knots is technically and intellectually challenging. Liu and Weizmann have found a way to manipulate nodes in molecules, which they can then combine to create extremely complex topologies. For this work, Liu received the Everett E. Gilbert Memorial Prize for the Best Third Year Experimentalist in Organic Chemistry in 2014.

Since DNA topology plays a profound role in several cellular processes, the researchers can use their method to study the mechanisms of key molecules. Liu focuses on an important group of enzymes called topoisomerases, which regulate DNA topology, and are important targets for cancer-fighting and anti-bacterial drugs. In future research, he plans to develop large-scale tests for topoisomerase inhibitors, and expand the use of DNA knots to study other enzymes.

Monika Scholz became interested in interdisciplinary research when she studied physics and microscopy at the Julius Maximilian University in Wurzburg and the Technical University in Dresden. The recipient of the Baron von Swaine scholarship, she spent a year at Harvard researching pathogenesis, where she was introduced to the study of the C. elegans worm. Her interest in the worm continued when she arrived at UChicago in 2012, as she began a project investigating the molecular basis of C. elegans behavior.

To accommodate this project, Scholz works at the intersection of the research groups of two UChicago scientists: Aaron Dinner, professor in chemistry; and David Biron, assistant professor in physics; as well as her former adviser at Harvard. Scholz’s goal is to build a comprehensive model of appetite in the C. elegans worm. Though appetite is a basic phenomenon in animals, it is poorly understood. Scholz plans to tease out the mechanisms that govern appetite in C. elegans by investigating the interactions of chemical cues and neural circuits. What role, for example, does the neurotransmitter serotonin play in regulating appetite?

Scholz has trained a series of microscopes on these worms, and tightly controls food levels and the worms’ exposure to neuromodulators. The microscopes collect a large number of images, which she has begun to characterize quantitatively. Her analysis has already yielded results that were not obvious from more traditional measurements of worm feeding, such as a time-dependent structure in the feeding behavior of C. elegans.

Boxuan Simen Zhao, a chemistry graduate student, joined the laboratory of Chuan He, professor in chemistry and Howard Hughes Medical Institute Investigator, in 2012 to study reversible RNA methylation. This is a critical process that produces a type of modified RNA that controls gene expression and development.

Zhao’s interest in proteins stems from research he performed as a Peking University undergraduate. In Peng Chen’s lab, he developed a fluorescent, protein-based probe that helps visualize organic hydroperoxides in living cells. This research was eventually published in the Journal of the American Chemical Society, and earned him first place in the “Challenge Cup,” a national competition for undergraduate science and technology research in China.

Zhao’s current research focuses on a type of protein called m6A reader proteins. He’s group has shown that reversible RNA methylation regulates genes that impact cell differentiation and development. Zhao is investigating certain proteins, such as hnRNP A2B1, that bind specifically to methylated RNA. Studying these proteins may elucidate the mechanisms of modification-mediated gene regulation, and open up new avenues of inquiry into processes where reversible RNA methylation is known to play a role, such as carcinogenesis and neurodegeneration.— Chelsea Leu