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Microscope Reveals a Little Splice of Life

Microscope Reveals a Little Splice of Life


Using laser scanning fluorescence microscopy, Boise State biophysicist Matt Ferguson is getting a close-up look at what’s happening inside living cells in real time.

Thanks to the Human Genome Project, we know that less than 2 percent of our genome contains protein-coding DNA sequences. But there’s still a lot to learn about how genetic information results in life as we know it through orchestrated transcription of various genes, translation of messenger RNAs into proteins and interactions of DNA, RNA and proteins.

“The Human Genome Project was completed about 15 years ago,” said Ferguson, assistant professor of experimental biophysics. “We now have all the letters in the book of life, but we don’t know the vocabulary, grammar or syntax to read and understand it.”

With funding from Boise State, Ferguson has built a two-photon orbital tracking microscope that can determine spatial and temporal dynamics of molecules inside living cells, their native environment. The microscope uses rapidly scanning laser beams to measure complex biological processes using multi-color fluorescent labeling techniques developed during his postdoctoral work at the National Cancer Institute.

But first, some background. DNA sequence is used to produce messenger RNA molecules, which are used by ribosomes to produce proteins according to that sequence. To make a mature messenger RNA, noncoding sections of RNA called introns need to be removed, and the sections left behind are joined together to form messenger RNA in a process known as splicing.

How the splicing process occurs at the single-molecule level is still a mystery to researchers. Ferguson’s work, published in eLife in October, helped to determine the speed of synthesis, how frequently RNA is produced and how long it takes to splice it, and the speed of release of RNA from the DNA template.

His article, titled “Kinetic competition during the transcription cycle results in stochastic RNA processing,” was recommended as being of special significance in its field by Faculty of 1000, an organization of leading biomedical experts.

Biophysics uses physics-based theories to study biological systems. “The physics side of this research is the building of equipment and analysis of the data,” Ferguson said. “You have to know how to model the physical process in order to extract relevant biochemical information.”

Ferguson’s latest research proposal was for work on the 4D Nucleome Project aimed at understanding the principles behind the organization and function of the nucleus in space and time (the fourth dimension). Nucleomes are structural units of a chromosome consisting of a length of DNA coiled around a core of histone proteins.