Subcellular protein localization in B. subtilis

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

In the last year, we have continued our studies that investigate how cells divide and differentiate in an effort to understand how these processes may fail during diseases like cancer. Specifically, this report will outline progress that we have made in the past year that extend our studies on how proteins localize and assemble during growth and development of the model organism Bacillus subtilis and in the human pathogen Staphylococcus aureus. Our lab first proposed that micron-scale membrane curvature can drive the subcellular localization of proteins. In the last year we have proposed a more detailed mechanistic model, which we termed the dash-and-recruit model, that describes how a morphogenetic protein localizes to convex membranes. Since the last report, we have published a multidisciplinary paper, incorporating in vitro and in vivo measurements, structural biology, and computer simulations, that described this mechanism. Our studies in B. subtilis cell division have recently prompted us to examine cell division in the human pathogen Staphylococcus aureus. We recently discovered that an essential cell division protein is sufficient to both promote the stable assembly of the division machinery and subsequently drive the disassembly of the machinery during cytokinesis. Since this single protein is instrumental for several steps of a critical cellular process, we envision that it may represent a novel antibiotic target. A manuscript describing this protein has been reviewed and is currently under revision. In a final project, our basic research recently led to the development of synthetic bacterial cells that we proposed could serve as a versatile display platform for vaccines. In collaboration with a group in NIAID, we have recently shown that these particles can deliver vaccines against S. aureus and that they provide superior protective efficacy against S. aureus in a murine bacteremia model of infection. A paper describing these results was accepted for publication and is currently in press.