Principal Investigator Darrell Irvine
Co-investigator Timothy Lu
Project Website http://isnweb.mit.edu/project-2.3.4.html
The research objective of this proposal is to engineer and test complementary wound-healing strategies, which include engineered bacteriophages that combat antibiotic-resistant wound pathogens and nanoparticles that deliver anti- inflammatory agents into mammalian cells. Multi-drug-resistant (MDR) bacteria opportunistically colonize battlefield-acquired wounds, especially when broad-spectrum antibiotics are used, resulting in tremendous mortality and morbidity. Inflammation plays a critical role in the wound-healing process by recruiting innate and adaptive immune cells to fight infection, but dysregulated inflammation is also a critical factor leading to failure in wound healing. Thus, there is a pressing need for new therapies to combat antibiotic-resistant superbugs and to achieve immunological homeostasis for optimal wound healing. We shall engineer and test bacteriophages as highly effective targeted therapies against antibiotic-resistant bacteria found in combat wounds. We will also utilize novel cell-penetrating nanoparticles to deliver anti-inflammatory proteins to mammalian cells. Finally, we shall evaluate the effectiveness of combined anti-bacterial and anti-inflammatory treatments. This work shall be conducted in close collaboration with the Walter Reed Army Institute of Research (WRAIR) Department of Wound Infection via Dr. Daniel Zurawski and Dr. Charles Li. This project is expected to benefit the ISN mission by yielding an entire new class of effective complementary therapies for enhancing wound healing in Wounded Warriors using the innovative combination of synthetic biology with nanotechnology.