Chemist Mingxu You Developing Next-Generation RNA-Based Probes

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Mingxu You, chemistry, recently received a five-year, $500,000 Faculty Early Career Development (CAREER) grant from the National Science Foundation (NSF) to develop a next-generation sensor platform that uses fluorescent bio-sensing probes and RNA molecules to image proteins, nucleic acids and small molecules in living cells. The versatile technique is expected to enhance cell biology studies and disease diagnostics.  

As You explains, scientists’ understanding of nature has largely relied on imaging tools, many of which are designed to be highly selective to a specific target. This leaves many important molecules in living systems for which there is no selective imaging tool. He says, “Fluorescent sensors have revolutionized our study of biology. Although powerful, current fluorescent sensors are not easily generalizable for detecting many cellular molecules. My lab is engineering a general system for performing selective intracellular imaging of essentially any target small molecule.”  

One of the goals is to use a regular fluorescent microscope in a new way, the bio-analytical chemist points out. “We want to develop a series of functional probes to allow us to see things that have not been seen before, such as intercellular force. Using a probe and dye in combination with a quencher chemical that can turn fluorescence on and off, the probe allows the user to see a bright fluorescence when there is mechanical force present.”

In this way, researchers will be able to measure tensile force, the “pulling apart force,” as You calls it. The biological consequences of mechanical force, known to be involved in tumor growth and wound healing, for example, are accessible with this technique. In the future he hopes to not only detect but to learn how to interfere with or regulate this process. Such RNA and DNA-based sensors can be broadly applicable in many clinical, industrial and ecological settings, he notes.

The project will also integrate sensor engineering research with scientific education and outreach. You is active in the Eureka! Program, a collaboration between the College of Natural Sciences and Girls Inc. of Holyoke, which offers summer research opportunities for female middle school students. Also You’s lab will involve undergraduate and graduate students in gaining experience in bioengineering, analytical chemistry and chemical biology. He also plans to assemble and mentor a team of undergraduates to take part in the International Genetically Engineered Machine (iGEM) competition.

The CAREER award is the NSF’s highest award in support of junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education and integrating education and research with their institution’s mission.