Dr. Ramamurthi’s laboratory studies fundamental mechanisms that cells use to differentiate and divide in an effort to understand how these processes may go awry during disease. His lab focuses on how proteins localize to particular subcellular locations and how they subsequently assemble to form large structures during development and cell division. Recently, he discovered that the shape of cellular membranes, either convex or concave, may recruit certain membrane shape-sensing proteins to their correct destination, a novel mechanism for subcellular protein localization.
A longstanding challenge in developmental biology is to understand how organisms construct large structures that ultimately help define how that organism looks. We are approaching this problem by examining the morphogenesis of a simple organism, a bacterial spore, and are trying to understand how it achieves its characteristic morphology. Spores are dormant cell types that are encased in a thick protein shell, termed the “coat”. Spores are highly resistant to environmental insults, and this resistance is due, in part, to the protective properties of the coat. Assembly of the basement layer of the coat depends on a tiny protein, called SpoVM, which anchors the coat onto the surface of the developing spore. We have discovered that SpoVM localizes properly by preferentially embedding in convex, or positively curved, membranes, such as those found on the surface of the spore. SpoVM then recruits a novel cytoskeletal protein, called SpoIVA, which polymerizes by hydrolyzing ATP to form a stable platform atop which other coat proteins eventually assemble. We are now employing genetic, biochemical, cytological, and biophysical approaches to understand the mechanisms by which these early events in coat assembly occur and how the self-assembly of the spore coat proceeds beyond these initial steps. Recently, we have reconstituted the assembly of the basement layer of the spore coat, using purified SpoVM and SpoIVA, around tiny silica beads surrounded by a lipid bilayer, to construct synthetic “spore-like” particles made entirely of defined components. We envision that these particles may be used as versatile platforms for the display of vaccines and drugs.
***Graduate students that are interested in a postdoctoral fellowship are encouraged to send their CV directly to Kumaran Ramamurthi (email@example.com)***
- Developmental Cell. 34: 682-693, 2015. [ Journal Article ]
- Nature Commun.. 6: 6777, 2015. [ Journal Article ]
- Proc Natl Acad Sci U S A. 112: E1908-1915, 2015. [ Journal Article ]
Asymmetric Division and Differential Gene Expression During a Bacterial Developmental Program Requires DivIVA.PLoS Genet. 10(8): e1004526, 2014. [ Journal Article ]
ATP Hydrolysis by a Domain Related to Translation Factor GTPases Drives Polymerization of a Static Bacterial Morphogenetic Protein.Proc Natl Acad Sci U S A. 110(2): E151-160, 2013. [ Journal Article ]
Kumaran Ramamurthi received his Ph.D. in Molecular Biology from the University of California, Los Angeles (UCLA), where he studied the secretion of bacterial virulence proteins. After a brief research fellowship at The University of Chicago, he studied subcellular protein localization as a Ruth L. Kirchstein National Research Service Award Postdoctoral Fellow at Harvard University.
He arrived at the NIH in 2009 as a Tenure Track Investigator and was promoted to Senior Investigator in 2016. He currently serves on the Editorial Board of The Journal of Biological Chemistry and is the Co-Director of the NIH-Johns Hopkins University Graduate Partnership Program. He received the National Cancer Institute Director’s Award in 2016.
|Amanda Decker||Postbaccalaureate Fellow (CRTA)|
|Thomas Delerue Ph.D.||Postdoctoral Fellow (Visiting)|
|Jailynn Harke||Postbaccalaureate Fellow (CRTA)|
|Minsuk Kong Ph.D.||Postdoctoral Fellow (CRTA)|
|Taylor Updegrove Ph.D.||Research Fellow|