In treatment of traumatic injury and disease, little is done to globally slow down biological processes. Essentially all current drug treatments focus on one target at a time. Global biostatic effects are achieved by, for example, cooling down a patient to slow cellular metabolism. It would be ideal to have a drug that similarly slows or pauses metabolism while non-specifically stabilizing cellular components to protect them from damage. Such a drug would be invaluable to traumatic injury treatment before emergency medical transport, diagnosis, or surgery, to reduce risk of death and extended injury by slowing the progression of blood loss, pathogenic infection, and organ damage. This technology could also be useful in preservation of protein therapeutics without refrigeration or in dehydrated form, preservation of blood products, preservation of tissues and organs for transplant, and new research tools leveraging temporary and targeted direct silencing across biological scales from proteins to specific cell types.

Some naturally-occurring intrinsically disordered proteins (IDPs) from organisms such as tardigrades (aka waterbears) or resurrection plants (time lapse below) that can undergo cryptobiosis (literally meaning “hidden life”) hold promise for their ability to slow degradation of biomolecules and protect cells from lethality during severe environmental exposures. We are using IDPs as a starting point for learning fundamental molecular bases for biostasis and design synthetic IDPs functionalized for efficacy and safety in human tissues using cutting-edge structure analysis and design software that we will extend for this application and synthetic biology tools for protein engineering. This work will lead to protein-based biostasis agents for which mechanism and safety will have been extensively tested in silico, biochemically, in cells and organoids, and in animal models.

Biostasis Concept

Researchers: Roger Chang, Dan Nguyen, Mike Veling, and Priya Jani in collaboration with Debora Marks (HMS), Jeffrey Way (Wyss Institute), Mike Springer (HMS), David Baker (UW-Seattle), and Ron Weiss (MIT).