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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011211-11
Application #
10014577
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Decker, Amanda R; Ramamurthi, Kumaran S (2017) Cell Death Pathway That Monitors Spore Morphogenesis. Trends Microbiol 25:637-647
Eswara, Prahathees J; Ramamurthi, Kumaran S (2017) Bacterial Cell Division: Nonmodels Poised to Take the Spotlight. Annu Rev Microbiol :
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
Updegrove, Taylor B; Ramamurthi, Kumaran S (2017) Geometric protein localization cues in bacterial cells. Curr Opin Microbiol 36:7-13
Ramamurthi, Kumaran S (2016) Editorial overview: Growth and development: prokaryotes. Curr Opin Microbiol 34:vii-viii
Wu, Yicong; Chandris, Panagiotis; Winter, Peter W et al. (2016) Simultaneous multiview capture and fusion improves spatial resolution in wide-field and light-sheet microscopy. Optica 3:897-910
Fu, Riqiang; Gill Jr, Richard L; Kim, Edward Y et al. (2015) Spherical nanoparticle supported lipid bilayers for the structural study of membrane geometry-sensitive molecules. J Am Chem Soc 137:14031-14034
Tan, Irene S; Weiss, Cordelia A; Popham, David L et al. (2015) A Quality-Control Mechanism Removes Unfit Cells from a Population of Sporulating Bacteria. Dev Cell 34:682-93
Gill Jr, Richard L; Castaing, Jean-Philippe; Hsin, Jen et al. (2015) Structural basis for the geometry-driven localization of a small protein. Proc Natl Acad Sci U S A 112:E1908-15
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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