Researchers from the University of Washington and the University of Trento in Italy have engineered a protein that blocks cancer-promoting “messages” in human cells, reports Eureka Alert.
The team described the tumor-busting protein in a paper published July 18 in Nature Chemical Biology.
The discovery follows a century of scientific research that has allowed us to understand the functioning of human cells as never before. The new engineered protein is just one example of a new class of treatments that try to take advantage of existing cellular mechanisms in order to treat diseases in a highly specific and powerful way.
Over a century of research has shined light on the once-murky innards of our cells, from the genes that serve as our “blueprints” to the proteins and other molecules that are our cellular taskmasters… Building on this basic knowledge, the search is underway for cellular mechanisms that could serve as gateways for new therapies.
UW chemistry professor Gabriele Varani told reporters that more exciting breakthroughs could be on their way. Varani claims that the technique used to engineer the cancer-blocking protein could be modified in a way that allows the scientists to engineer proteins that help to fight other diseases and ailments. It would simply be a matter of understanding the cellular messages and functions that need to be targeted in order to fight a given disease, said the senior author.
“What we show here is a proving ground — a process to determine how to make the correct changes to proteins.”
Phys.org reports that researchers are using arrays to understand the function of cells, especially microRNA strands, in a way that will allow them to target pancreatic ailments and diseases like diabetes.
MicroRNA strands were once thought of as junk genetic material. Now, researchers know that these small structures help program surrounding genes, affecting everything from eye color to cancer. If DNA is like a blueprint, then RNA is the ink; it serves as the messenger between the genetic code stored in DNA and the molecules that are built following the blueprint model.
A team including Xiaoqing Tang, assistant professor of biology at Michigan Technological University, examined an array of MicroRNA — small RNA molecules — to try to understand how it works. Tang examined which strands were active in beta cells, which secrete insulin, and which strands were active in alpha cells, which secrete glucagon, a substance that regulates blood sugar levels
Only a few stood out, and one – miR-483 – shows a clear pattern.
The team who engineered the cancer-blocking protein did it by modifying a human protein called Rbfox2. This protein occurs naturally in cells and binds to microRNAs.
[MicroRNAs] adjust gene expression levels in cells like a dimmer switch.
Varani’s group sought to engineer Rbfox2 to bind itself to a specific microRNA called miR-21, which is present in high levels in many tumors.
miR-21 has been found to increase expression of cancer-promoting genes and decreases cancer suppressors. Varani’s team reasoned that, if a protein like Rbfox2 could bind to miR-21, it could repress tumor growth effects.
One challenge facing the team was that they would have to create a protein that binds bind to miR-21 and no other microRNA. The team took advantage of the fact that all RNA molecules, including microRNAs, consist of a chain of chemical nodes that “imbues them with specificity.”
Phys reports that Varani’s team were the first in history to manage to successfully alter a protein to bind to microRNAs.
Varani told reporters that this is because proteins have long been well-understood, but RNAs have not.
“That is because our knowledge of protein structure is much better than our knowledge of RNA structure. We historically lacked key information about how RNA folds up and how proteins bind RNA at the atomic level.”
The team believe that the protein they modified, Rbfox2, could be altered again to bind to microRNA targets other than the cancer-promoting miR-21 microRNAs.
[Photo by Sean Gallup/Getty Images]