葫芦影

Chemist and Biologist Develop Technique to Measure Molecular Binding Strength

Shoujun Xu and Yuhong Wang Awarded NSF Grant

Professor of chemistry Shoujun Xu and professor of biology and biochemistry Yuhong Wang are bringing their expertise together to develop a new imaging technique at the 葫芦影业.

Shoujun Xu
Shoujun Xu, professor of chemistry, and his lab invented the super-resolution force spectroscopy technique that measures the binding strength of two biological entities.

The researchers are creating a technique called force-modulated fluorescent resonance energy transfer (fmFRET) microscopy. It combines the super-resolution force spectroscopy technique invented by Xu鈥檚 lab with the FRET microscopy developed in Wang鈥檚 lab.

Xu鈥檚 force spectroscopy measures the binding strength of two biological entities. Those could be DNA-DNA bonds or protein-protein bonds, for example. With his atomic magnetometer, magnetic particles and acoustic radiation generate a mechanical force that pulls apart the bond between two molecules in order to measure the bond. The precise measurements are at a resolution of about one piconewton. Such a resolution is nearly 10 times better than current competing techniques, sufficient to distinguish DNA-DNA bonds at the smallest unit.

Yuhong Wang
Yuhong Wang, professor of biology and biochemistry, peers into her lab鈥檚 multicolor single molecule FRET microscope. In step with Xu鈥檚 technique, Wang鈥檚 microscopy will be used to probe the dynamics of molecules.

However, 鈥渢here鈥檚 a limitation,鈥 said Xu, principal investigator and faculty at the College of Natural Sciences and Mathematics. 鈥淲e can only do one sample at a time.鈥

This is where Wang鈥檚 microscope comes in to label multiple molecular samples using her fluorescent microscopy.

鈥淭he multiplex FRET microscope can detect six pairs of different fluorescently labeled molecules to probe their dynamics,鈥 said Wang.

Paving the Road to Wide Applicability of New Techniques

Shoujun Xu
Xu works on his research group鈥檚 atomic magnetometer.

Two major applications will be explored using the new technique. One application will allow researchers to better understand how the ribosome reads messenger RNA to produce correct proteins and could potentially guide drug design to treat viral infections.

Normally, the ribosome, which makes proteins along the messenger RNA, moves by three nucleotides at a time. However, sometimes, it moves by only two.

鈥淭hat鈥檚 what we call frameshifting,鈥 Xu said. 鈥淎 lot of viruses use frameshifting to make their different proteins. Our role is to figure out when this happens and how many steps they move.鈥

Another application of their technique involves widespread use of Xu鈥檚 atomic magnetometer in biological research.

鈥淰ery, very few chemists, use it for studying biological systems,鈥 he said. 鈥淗opefully we can use what we learned about the force and magnetic detection and expand it with FRET detection to make it much more feasible to other researchers.鈥

Both Xu and Wang thank UH鈥檚 Division of Research for providing the equipment necessary for their experiments. 鈥淒eveloping this new technique would not have been possible without DOR鈥檚 support,鈥 Xu said.

Their work is funded by a recent $519,045 grant from the National Science Foundation. Xu and Wang have collaborated for more than 10 years.

- Rebeca Trejo, College of Natural Sciences and Mathematics

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