Peter Chien, biochemistry and molecular biology, recently received a five-year, $1.8 million NIH Maximizing Investigators’ Research Award (MIRA) award to fund research into how bacterial cells manage stress responses. Because antibiotics pose a major stress for these microbes, the work will in part address what he calls “the alarming rise in multi-drug resistant bacteria.”
Chien, who is director of the Models to Medicine Center in the Institute of Applied Life Sciences at UMass Amherst, says that most bacteria are now resistant to commonly used antibiotics, and “the protease-based pathways we study in our lab represent new avenues to target as we look for new ways to fight drug resistance.” As director, he adds, “My goal is to move basic research into applied directions, to facilitate things like this research making an impact on a real-life problem.”
The MIRA program, initiated in 2015 by the director of the National Institute of General Medical Sciences, does not fund individual projects, but instead broad programs of basic discovery research that meet the institute’s focus areas. The idea is to encourage researchers to propose more long-term, innovative, creative projects and to worry less about short-term goals and results. Institute leaders noted that investigators who must constantly worry about loss of funding may lead to overly conservative proposals.
Chien says, “Because this award funds the lab and not specific narrow questions like most NIH grants, we can pursue unexpected new directions of research as they are discovered during our work. This MIRA grant will let us be truly creative and train our students in the best possible way with the most cutting edge approaches.”
Biochemists have long known that many key cell processes depend on a highly regulated cleanup system in which specialized proteins called proteases degrade damaged or no-longer-needed proteins, Chien says. Proteases must specifically destroy their targets without damaging other proteins, and for years he and colleagues have been studying and revealing the details of how this orderly destruction works.
He explains, “Bacteria must navigate hostile environments during both normal and infectious stages. The pressing need for new antibiotics means that research must target novel bacterial pathways to combat lethal infections. In my lab, we study bacterial proteases, which are critical enzymes that destroy other proteins in order to help cells manage different types of stress.”
Recently, the Chien lab discovered new regulators of these proteases that help bacteria develop from one cell type to another, in a way similar to how bacteria transform from benign to infectious forms. The research also showed how proteases can be selectively activated during stress to stop cells from growing in order to repair damages. Because protease activity is crucial to developing virulence in bacterial pathogens, understanding how these adaptors are controlled could be used to develop new classes of antibiotics.
Chien points out that he is not the first in his department to obtain the coveted MIRA award. Lila Gierasch, Distinguished Professor of Biochemistry, and Dean Tricia Serio of the College of Natural Sciences are also recipients. Chien says, “It is fantastic that NIGMS is investing in researchers and letting us determine the direction for the most important science.”