See last line, I immediately saw this as a possible solution to the neuronal cascade of death in the first week. What did your doctor see when reading this? ABSOLUTELY NOTHING? Because it wasn't read or your doctor didn't make the connection to stroke rehab?
World’s Most Resilient Organism Could Hold Key to Wound Healing
Although climate change has the potential to wipe out some species, there is one organism that can withstand nearly any condition that may outlast them all: tardigrades.Now a group of scientists at the Harvard Medical School (HMS) plan to embark on a challenging science endeavor: developing a protein-based therapy, inspired by tardigrade proteins.
Tardigrades, one of the most resilient organisms on Earth, can thrive in almost any extreme condition from high temperatures to radiation, to carbon dioxide and chemical exposure, making them the perfect organism to study for developing a protein-based therapy to halt tissue damage, as they experience a state called cryptobiosis.
Cryptobiosis is a physiological state that allows tardigrades to survive extremely dry conditions. When this physiological state occurs, biochemicals are deployed to protect nucleic acids and proteins from damage due to conditions that are not ideal.
These biochemicals include proteins called intrinsically disorder proteins (IDPs), which are able to slow down cellular activity. But scientists have struggled to understand their function and their structure.
The research team—including Pamela Silver, the project’s principal co-investigator and professor of systems biology at Harvard; Roger Chang, a bioinformatician and molecular biologist in Silver’s lab; and Debora Marks, a machine learning and computation expert—are working to harness this protective mechanism in tardigrades and develop a disordered protein for traumatic injuries.
The project formed when Silver discovered a U.S. military grant challenge searching for a solution to halt bleeding and tissue necrosis in traumatic injury.
Chang, a researcher in protein resistance, discovered previously that E. coli and yeast were more tolerant to extreme dryness when tardigrade proteins were introduced.
“I started conceiving how we could improve upon nature’s ‘raw’ materials and functionalize them for human use,” Change said.
But creating disordered proteins is an extremely complex task because the shape of the protein determines its function—and there are endless possibilities.
The project, funded by the Defense Advanced Research Projects Agency (DARPA) for $14.8 million, aims to first decipher the structure and function of the tardigrade proteins that play a role in how they withstand intolerable conditions. The researchers will then engineer proteins that slow metabolic activity in injured cells, potentially leading to a protein-based therapy.
Designing the protein would comprise a string of amino acids that determine the shape, which then determines the function. The engineered protein must also be able to bypass the immune system without causing an antibody response, and the researchers will have to understand how the structure would impact other cellular components. The therapy would eventually be tested in human organoids and animals.
To eliminate the infinite amount of sequence possibilities, the researchers will utilize computer modeling.
“This is not a black-box approach where we throw in every possible combination and put in a load of features, and see what sticks,” Marks said. “It is a form of unsupervised machine learning that doesn’t presume an outcome. The universe of possible protein sequences is infinite, so we want to be directed and targeted.”
“The vision is to have a test bed where we can deploy lots of different styles of these proteins and find out which are the best,” Silver added. “The ultimate dream would be to design totally new proteins, never seen before. The work can then become a new platform for designing proteins.”
Not only do the researchers plan to develop a therapy for traumatic injury on the battlefield, they are also planning to create a therapy for long term therapeutic benefits including heart attacks, strokes, wounds and sepsis.
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