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Search for common traits of 'survivor cells' could help uncover cancer’s Achilles' heel

September 26, 2016

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A new research initaitive, led by Silke Hauf, will attempt to identify traits that help some organisms continue to function under extreme conditions.

Most cells raised in research labs live a pretty pampered life: every aspect of their environment, from temperature to nutrient levels, is carefully controlled to ensure they thrive and multiply.

The cells in Silke Hauf’s lab won’t be quite so spoiled. Based at the Biocomplexity Institute of Virginia Tech, Hauf and a team of international collaborators are working to identify traits that help some organisms continue to function despite extreme variations in their surroundings and internal composition—an effort supported by a new $1.8 million grant from the National Institutes of Health.

If Hauf’s specimens have a rougher time than most, it’s for a good cause. Finding traits that allow cells to survive stress and internal imbalance could be a major boon to engineers of synthetic organisms. Conditions outside the lab can’t be carefully controlled, so a microorganism designed to consume toxic chemicals after an oil spill, for example, needs to be robust enough to endure sudden changes in its surroundings.

Cancer cells, on the other hand, typically seem to prosper under extreme circumstances.  Certain mutations help them thrive in low-nutrient, low-oxygen environments, allowing them to overproduce and crowd out healthy cells. If Hauf’s team can identify a tipping point where cancer cells’ beneficial mutations become self-destructive, scientists could potentially engineer new treatments to give them an extra push over that precipice.

“We’re diving into a little-explored area of molecular biology, so this project could take us in a number of exciting directions,” said Hauf, a Biocomplexity Institute fellow and assistant professor in Virginia Tech’s Department of Biological Sciences in the College of Science. “The fantastic thing about this new type of grant is that it gives us the flexibility to adjust our focus and chase down promising leads as they emerge.”

This current line of inquiry builds on Hauf’s previous work demonstrating that some cellular functions begin to misfire when a precise balance of signaling proteins isn’t upheld. Now, backed by simulation technology capable of predicting how specific variables are likely to impact cell survivability, Hauf hopes to hone in on what distinguishes these highly sensitive mechanisms from those that easily accommodate change.

“On the whole, it’s unlikely there’s going to be one particular protein or a single gene that separates robust and fragile cells,” said Hauf. “Experimenting in a simulation environment gives us the freedom to test many assumptions at once and maintain a big picture perspective about how these cellular dynamics function and feed into one another.”

Ambitious in its scope, this research initiative has been fully funded through the National Institutes of Health’s prestigious Maximizing Investigators’ Research Award. Historically this grant has only been available to the most thoroughly established figures in the medical sciences, but the National Institutes of Health recently issued its first-ever call for proposals from early-career researchers. Hauf’s project was selected from a highly competitive pool of national candidates to receive this award.

“Dr. Hauf’s research brings a remarkable new dimension to the already-powerful programs in cancer and systems cell biology on our campus,” said Brenda Winkel, head of Virginia Tech’s Department of Biological Sciences. “Moreover, she is a wonderful example of how partnerships between academic departments and the research institutes can help recruit and support faculty who embody Virginia Tech’s commitment to providing world-class training for students as they tackle the most urgent problems facing our world today.”

Written by Dan Rosplock.

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