Stem cells help researchers peg rabies resistance

COLLEGE STATION Researchers at Texas A&M AgriLife Research have developed a new technology to determine sensitivity or resistance to rabies virus.

We were able to create a novel platform such that we could look at how pathogens, such as bacteria or virus or even drugs or radiation, interact with specific human genes, said lead researcher Dr. Deeann Wallis, AgriLife Research assistant professor of biochemistry and biophysics. It allows us a new way to profile the genes involved in sensitivity or resistance to certain agents.

The rabies work is being reported in the journal Stem Cells.

Our study is the first to show pre-existing libraries of mutant stem cells can be differentiated into different cell types en mass and screened to identify meaningful genes involved in a cells response to infection, Wallis said. Moreover, this technique can be used to identify human genes that are involved in any type bacterial or viral infection, or even response to drugs, toxins or radiation. This is a relatively novel way for researchers to discover gene function and assess human host response.

Understanding sensitivity or resistance to rabies is important, she said, not only because the disease still causes 55,000 deaths a year globally, but it could also potentially be weaponized and used as a biowarfare agent.

Wallis said the five-year study used murine embryonic stem cells from a library of mutant stem cells typically used to generate knockout mice.

A knockout mouse is a laboratory mouse in which researchers have inactivated, or knocked out, an existing gene by replacing it or disrupting it with an artificial piece of DNA, according to the National Human Genome Research Institute. Such cells and mice are frequently used as a model to study human genes, Wallis noted.

She explained that each stem cell clone has a different gene mutated.The researchers took a panel of a variety of different genes and were able to query each cell line separately.

For the first time ever, we were able to take thousands of different stem cell lines, each carrying a separate mutation, and differentiate them into neurons, she said. It was quite a large task to miniaturize this. We were able to show with genes that are known to be involved in rabies virus that if we mutated a gene in the mouse, we still can see differences in sensitivity and resistance to rabies virus in these cells.

Knockout mouse stem cells have only one copy of each gene, whereas a regular cell would have two copies of every gene. Therefore, other researchers thought it was not possible to see an impact of a particular gene because half of it is still there, she said.

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Stem cells help researchers peg rabies resistance