October 11, 2012

VU recruit’s work lights up genetic ‘dark matter’

They’ve been called “junk DNA” and genetic “dark matter” — the long segments of the human genome (98 percent of it) that do not encode protein.

They’ve been called “junk DNA” and genetic “dark matter” — the long segments of the human genome (98 percent of it) that do not encode protein.

Gregor Neuert, Ph.D., M.Eng., and colleagues are studying the long segments of the genome. (photo by Steve Green)

Increasingly, scientists are discovering that these mystery pieces of DNA and their corresponding RNA transcripts are not junk at all, but play an important role in regulating gene expression.

One of these researchers is Gregor Neuert, Ph.D., M.Eng., assistant professor of Molecular Physiology and Biophysics, who arrived at Vanderbilt University this summer after completing a postdoctoral fellowship at the Massachusetts Institute of Technology (MIT).

Neuert is a biophysicist from Germany who uses quantitative single-cell experiments, genetics and mathematical models to understand how genes are regulated and how signals are transmitted across cell membranes.

In the Sept. 14 issue of the journal Cell, he and colleagues at MIT reported the discovery of long, non-coding pieces of RNA (more than 300 base pairs in length) that actually guide reproduction in budding (brewers) yeast, a well-studied one-celled microorganism.

Single-molecule RNA FISH
Single-molecule RNA fluorescence in situ hybridization, a microscopy technique adapted by Gregor Neuert, shows expression of messenger RNA (green and red dots) in single human cancer cells. Cell nuclei are blue. (Neuert lab)

“These long non-coding RNAs are important in inducing gametogenesis, a process that produces sperm and eggs in humans and spores in budding yeast,” Neuert said. “If you understand how these long non-coding RNA function in yeast … then maybe we also find out what are good approaches for studying them in mammalian cells.”

To confirm the role of these RNAs in spore production, Neuert adapted a microscopy technique called single-molecule RNA FISH (fluorescence in situ hybridization), which uses fluorescent probes to detect individual RNA molecules in single cells.

The technique may be useful in studying the role of other coding and non-coding RNAs in higher organisms and in diseases such as cancer, he said.

Neuert, who earned a Ph.D. in Molecular Biophysics at Ludwig Maximilians University Munich, said he came to Vanderbilt to apply his expertise to mammalian and disease-related research.

Single-molecule RNA fluorescence in situ hybridization shows expression of long non-coding RNA (red dots) and coding RNA (green dots) in individual yeast cells. Cell boundaries are purple and nuclei are blue. (Neuert lab)

“I think Vanderbilt is an excellent environment for that,” Neuert said, “because it emphasizes a very strong attitude toward basic research but it also has the clinical side. They are right next to each other. I don’t think there are many places that can offer that.”

“This is, for me, the right environment because I can bring very quantitative approaches to biology and medicine, and on the other side, there is much for me to learn,” he said. “One of the long-term goals will be to bring these tools from yeast and basic research potentially into the clinic.”

The research conducted at MIT was partly supported by the National Institutes of Health (grant No. U54CA143874) and the National Science Foundation (grant No. ECCS-0835623).