New sequencing technology helps researchers understand brain cell development

brainFor many years, neuroscientists have focused on the role of neurons in brain development nearly to the exclusion of all else. Recent discoveries powered by genomic sequencing are standing accepted theories of brain development on their heads.

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Glial cells, particularly astrocytes, outnumber neurons in the brain. Astrocytes touch every part of the brain, their star-shaped fingers reaching into the innermost recesses of that organ. They serve the important function of clearing glutamate, a chemical byproduct of synaptic response, from neurons. If the astrocyte cannot clear the glutamate, neurons can become overstimulated, leading to diseases like epilepsy, Parkinson’s, or Alzheimer’s. They are therefore important to behavior, cognition, and autonomic function, like breathing.

Only in the past few years, however, has the importance of astrocytes been truly recognized. Researchers are now delving more deeply into their function and development.

Michelle Olsen, associate professor in the School of Neuroscience at Virginia Tech, is making use of next-generation sequencing opportunities available at the Biocomplexity Institute’s Genomics Sequencing Center (GSC) to peer more deeply into the inner workings of astrocytes. With the GSC’s new Illumina NovaSeq 6000, the development of astrocytes can be studied at a granular level. The School of Neuroscience is part of the Virginia Tech College of Science.

“One thing we don’t really understand is how astrocytes develop in young humans,” Olsen said. “They come online during the third trimester and are so complex. They interdigitate into everything, and yet we still don’t understand the changes in genes and protein expression that allow this to happen.”

Olsen is working to uncover the links between astrocytes and phenotypes in brain development. What are the changes over time that should lead to normal development? If abnormalities occur, at what point do they crop up and why?

The institute’s NovaSeq 6000 helps Olsen study astrocyte genetic expression in rats and mice. At certain checkpoints along the timeline of development, the astrocytes of the rodents are sequenced to give a snapshot of their development over time. Olsen is therefore able to see not only what is normal in astrocyte proliferation but when each step in the process occurs.

“If we know each step of the process of astrocyte development, we can really understand disease because we’ve produced a baseline for what normal is,” Olsen said.

The NovaSeq System, developed by Illumina, is the most powerful high-throughput sequencer available today. It enables large-scale genomics projects like Olsen’s to be completed quickly, easily, and cost-effectively.

“The NovaSeq and NextSeq instruments greatly expand the capacity of the GSC, enabling us to provide more cost-effective, timely, and enhanced services to our research faculty within Virginia Tech,” said Stanley Hefta, director of the GSC.

Using instruments like the NovaSeq 6000 allows Olsen the scope to understand how astrocytes function and the consequences of dysfunction. A focal point of Olsen’s studies is Rett syndrome, a particularly devastating neurological disorder that usually affects girls from 18 to 20 months of age. Babies with Rett syndrome are deficient in an X-linked gene, MECP2, which when absent in astrocytes causes neurological difficulties, such as hand tremors, seizures, and even loss of the ability to swallow.

“It’s very moving going to conferences and seeing the families of these children,” Olsen said. “If we could even incrementally improve the quality of life for a patient, we’d have a powerful impact.”

What Olsen may find next will have lasting impact on brain science and help those struggling with genetic mutations that up until now have not been well understood. Next-generation sequencing technology at the institute is helping researchers achieve fantastic new insights into the inner workings of the brain.

To hear Olsen speak about her work, register now for the Biocomplexity Institute’s HPC+ GSC Open House on May 22.

About the GSC

The Biocomplexity Institute’s Genomics Sequencing Center is a one-stop shop for the development and application of state-of-the-art next-generation sequencing technologies. Researchers are provided rapid and cost-effective, high-quality experimental design, data, and data analysis by genomics experts.

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