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 has extended our analysis on the assembly of the bacterial spore coat as a model for understanding cellular morphogenesis. We have described a molecular ratchet model to explain the initiation of coat assembly in B. subtilis spores- a novel mechanism for how a supramolecular structure initiates self-assembly. A manuscript describing these results is currently under revision for publication. We have also described how the major structural component of the the basement layer utilizes ATP hydrolysis to self assemble around the developing spore. Finally, we have identified a previously uncharacterized chaperone protein that is required for proper assembly of the spore cell surface. Previously, we have used our basic science discoveries to develop artificial bacterial spore-like particles that we proposed can be used as novel drug delivery vehicles. In the last year, we have engineered these particles to contain a sample drug cargo and have modified the surface of these particles to directly bind to certain epitopes that are overrepresented on cancer cells. We have demonstrated, in a mouse model, that these particles are safe when administered and can prevent the growth of tumors. A manuscript describing these results is currently under preparation for publication.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Kim, Edward Y; Tyndall, Erin R; Huang, Kerwyn Casey et al. (2017) Dash-and-Recruit Mechanism Drives Membrane Curvature Recognition by the Small Bacterial Protein SpoVM. Cell Syst 5:518-526.e3
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Decker, Amanda R; Ramamurthi, Kumaran S (2017) Cell Death Pathway That Monitors Spore Morphogenesis. Trends Microbiol 25:637-647
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Wu, I-Lin; Narayan, Kedar; Castaing, Jean-Philippe et al. (2015) A versatile nano display platform from bacterial spore coat proteins. Nat Commun 6:6777

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