Kumaran S. Ramamurthi, Ph.D.
Kumaran S. Ramamurthi, Ph.D.
Investigator
Head, Cell Biology Unit

Center for Cancer Research
National Cancer Institute

Building 37, Room 5132
Bethesda, MD 20892
301-451-8792

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.

Areas of Expertise
1) Microbiology 2) Protein trafficking 3) Cellular differentiation 4) Cell division 5) Cytoskeleton 6) Fluorescence microscopy

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 a spore ends up looking like a spore. When the rod-shaped bacterium Bacillus subtilis faces starvation, it elaborates a spherical internal organelle that will eventually mature into a spore, a dormant cell type that protects the bacterium's genetic material from environmental onslaughts. As the spore matures, the bacterium deposits a thick protein shell, called the spore coat on the surface of the developing spore which will eventually protect the spore when it is released. The spore coat is composed of some seventy different proteins, is the outermost structure of the spore, and is what makes a spore look like a spore.

How is the spore coat assembled? Assembly of the massive coat depends on a tiny peptide, called VM, which anchors the coat onto the surface of the developing spore. How does the peptide localize to the right place? We have discovered that the convex, or positively curved, membrane surface of the developing spore is a landmark that VM recognizes and that this geometric cue recruits VM to its proper subcellular location. Next, VM recruits another protein, called IVA, which then polymerizes by hydrolyzing ATP to form a stable platform atop which every other coat protein sequentially assembles. Protein sorting driven by a geometric cue, and protein assembly driven by ATP hydrolysis, are novel mechanisms for the assembly of a supramolecular structure. We are now employing genetic, biochemical, cytological, and biophysical approaches to understand the detailed mechanisms of how these early events in coat assembly occur and how the self-assembly of the spore coat proceeds beyond these initial steps.

***Graduate students that are interested in a postdoctoral fellowship are encouraged to send their CV directly to Kumaran Ramamurthi (ramamurthiks@mail.nih.gov)***

Scientific Focus Areas:
Cell Biology, Microbiology and Infectious Diseases, Molecular Biology and Biochemistry
Selected Key Publications
  1. Eswaramoorthy P, Winter PW, Wawrzusin P, York AG, Shroff H, Ramamurthi KS
    PLoS Genet. 10(8): e1004526, 2014. [ Journal Article ]
  2. Castaing JP, Nagy A, Anantharaman V, Aravind L, Ramamurthi KS.
    Proc Natl Acad Sci U S A. 110(2): E151-60, 2013. [ Journal Article ]
  3. Ebmeier SE, Tan IS, Clapham KR, Ramamurthi KS
    Mol Microbiol. 84(4): 682-96, 2012. [ Journal Article ]
  4. Eswaramoorthy P, Erb ML, Gregory JA, Silverman J, Pogliano K, Pogliano J, Ramamurthi KS
    MBio. 2(6): e00257-11, 2011. [ Journal Article ]
  5. Ramamurthi KS, Lecuyer S, Stone HA, Losick R
    Science. 323(5919): 1354-7, 2009. [ Journal Article ]

Kumaran Ramamurthi received his Ph.D. in Molecular Biology from the University of California, Los Angeles where he studied secretion of bacterial virulence proteins with Prof. Olaf Schneewind. He then studied subcellular protein localization as a National Research Service Award postdoctoral fellow with Prof. Richard Losick at Harvard University. He arrived at the NIH in 2009.

Name Position
Jenny Barriga Postbaccalaureate Fellow
Prahathees Eswara Moorthy Ph.D. Postdoctoral Fellow (CRTA)
Edward Y Kim Postdoctoral Fellow (CRTA)
Irene S. Tan Predoctoral Fellow
I-Lin Wu Postdoctoral Fellow (Visiting)

Summary

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.

Areas of Expertise
1) Microbiology 2) Protein trafficking 3) Cellular differentiation 4) Cell division 5) Cytoskeleton 6) Fluorescence microscopy

Research

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 a spore ends up looking like a spore. When the rod-shaped bacterium Bacillus subtilis faces starvation, it elaborates a spherical internal organelle that will eventually mature into a spore, a dormant cell type that protects the bacterium's genetic material from environmental onslaughts. As the spore matures, the bacterium deposits a thick protein shell, called the spore coat on the surface of the developing spore which will eventually protect the spore when it is released. The spore coat is composed of some seventy different proteins, is the outermost structure of the spore, and is what makes a spore look like a spore.

How is the spore coat assembled? Assembly of the massive coat depends on a tiny peptide, called VM, which anchors the coat onto the surface of the developing spore. How does the peptide localize to the right place? We have discovered that the convex, or positively curved, membrane surface of the developing spore is a landmark that VM recognizes and that this geometric cue recruits VM to its proper subcellular location. Next, VM recruits another protein, called IVA, which then polymerizes by hydrolyzing ATP to form a stable platform atop which every other coat protein sequentially assembles. Protein sorting driven by a geometric cue, and protein assembly driven by ATP hydrolysis, are novel mechanisms for the assembly of a supramolecular structure. We are now employing genetic, biochemical, cytological, and biophysical approaches to understand the detailed mechanisms of how these early events in coat assembly occur and how the self-assembly of the spore coat proceeds beyond these initial steps.

***Graduate students that are interested in a postdoctoral fellowship are encouraged to send their CV directly to Kumaran Ramamurthi (ramamurthiks@mail.nih.gov)***

Scientific Focus Areas:
Cell Biology, Microbiology and Infectious Diseases, Molecular Biology and Biochemistry

Publications

Selected Key Publications
  1. Eswaramoorthy P, Winter PW, Wawrzusin P, York AG, Shroff H, Ramamurthi KS
    PLoS Genet. 10(8): e1004526, 2014. [ Journal Article ]
  2. Castaing JP, Nagy A, Anantharaman V, Aravind L, Ramamurthi KS.
    Proc Natl Acad Sci U S A. 110(2): E151-60, 2013. [ Journal Article ]
  3. Ebmeier SE, Tan IS, Clapham KR, Ramamurthi KS
    Mol Microbiol. 84(4): 682-96, 2012. [ Journal Article ]
  4. Eswaramoorthy P, Erb ML, Gregory JA, Silverman J, Pogliano K, Pogliano J, Ramamurthi KS
    MBio. 2(6): e00257-11, 2011. [ Journal Article ]
  5. Ramamurthi KS, Lecuyer S, Stone HA, Losick R
    Science. 323(5919): 1354-7, 2009. [ Journal Article ]

Biography

Kumaran Ramamurthi received his Ph.D. in Molecular Biology from the University of California, Los Angeles where he studied secretion of bacterial virulence proteins with Prof. Olaf Schneewind. He then studied subcellular protein localization as a National Research Service Award postdoctoral fellow with Prof. Richard Losick at Harvard University. He arrived at the NIH in 2009.

Team

Name Position
Jenny Barriga Postbaccalaureate Fellow
Prahathees Eswara Moorthy Ph.D. Postdoctoral Fellow (CRTA)
Edward Y Kim Postdoctoral Fellow (CRTA)
Irene S. Tan Predoctoral Fellow
I-Lin Wu Postdoctoral Fellow (Visiting)