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 with an emphasis on how this assembly process may be monitored during during growth and development of the model organism Bacillus subtilis. In multicellular organisms, individual cells routinely sacrifice themselves for the benefit of the organism as a whole, such as when one cell is damaged beyond repair or is infected with a virus. However, in unicellular organisms such as bacteria, it has been unclear if single cells in a population could be programmed to commit altruistic suicide for the clear benefit of their brethren. We have now identified such a pathway in a bacterium that forms a cell type called a spore that is dormant and is resistant to many environmental insults. The pathway that we discovered monitors the process of spore formation. In cells that make a mistake in assembling a strong shell that protects the spore, the pathway induces degradation of a structural protein required to form this shell, resulting in the lysis of that individual bacterial cell, thereby removing it from the population and ensuring that the genomes of the cells that become dormant spores remain mistake-free. These results were published in September, 2015 in Developmental Cell. Interestingly, in metazoans, not only is the degradation of a structural proteins, nuclear lamins, is a hallmark of apoptosis, but the misassembly of nuclear lamins itself can trigger apoptosis. However, the mechanism by which the assembly of such structures is monitored is poorly understood. Using the powerful genetics of B. subtilis, we hope to answer how the assembly of large biological structures in general may be monitored to trigger a cellular response when their assembly is compromised. Our studies in B. subtilis cell division have recently prompted us to examine cell division in the human pathogen Staphylococcus aureus. We have recently discovered a cell division protein that 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. These results have been submitted for publication.
| 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 |
| 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 : |
| 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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