Now armed with that knowledge, Heuck and graduate student Yu-zhou Tang and others plan to use a special microscope to watch the organization of the channels at the single-molecule level. The will use multiple biochemical and biophysical methods, combined with fluorescent labeling of amino acids one at a time, to map two key protein translocators, Pseudomonas outer protein (Pop) B and D, and to figure out how they are assembled and how they form a translocon channel into a target cell.
With PopB and PopD, the biochemists can create a stable pore in model membrane for studying the relative quantities of different proteins, technically known as the stoichiometric arrangement, involved in T3S translocon assembly.
"No one has any idea right now how the PopB and PopD proteins get together, what it looks like when they fit together to form the channel. But it's important knowledge. If you want to know how to block these proteins from infecting the target cell, you must know how they are getting in and how they attack," Heuck says.
In five years, Heuck and colleagues hope to be able to offer hope to cystic fibrosis patients, many of whom lose their lives to Pseudomonas bacteria because at present, doctors run out of antibiotics that are effective against it. Further, many of these pathogens are listed as bioterrorism agents by the U.S. Centers for Disease Control and Prevention. It could become very important in the future to be able to mount an entirely new defense against their extremely effective methods of infecting populations with virulent bacterial diseases.
As he embarks on this major five-year study, Heuck says he is grateful to have received a bridge grant of $15,000 from UMass Amherst's Faculty Research/Healey Endowment Grant that allowed him to keep his lab open, actively gathering preliminary data to use
|Contact: Janet Lathrop|
University of Massachusetts at Amherst