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2128 TAMU Office: Lab: Fax: 979-862-4718 |
Biography |
| Ry Young did his undergraduate work at CalTech and Rice, graduating with an A.B. in Biochemistry from Rice in 1968. After serving in the U. S. Navy during the Vietnam War, he earned a Ph.D. in Molecular Biology as a National Science Foundation Fellow under Hans Bremer at the University of Texas at Dallas. After postdoctoral work as an NIH Fellow at Harvard Medical School, he joined the faculty of the Department of Medical Biochemistry in the Texas A&M College of Medicine in 1978. He moved to the Department of Biochemistry and Biophysics in 1986 and is now a Professor of Biochemistry and Biophysics and also a joint faculty member of Biology. | |
| Molecular Mechanisms of Host Cell Lysis | |
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The Young laboratory is primarily focused on the molecular mechanisms by which bacteriophages, or bacterial viruses, accomplish host cell lysis. Bacteria have a sturdy cell wall made up of a cross-linked polysaccharide derivative called the peptidoglycan. This incredibly strong and rigid structure keeps the membrane sac of the cell from blowing up like an overfilled balloon, yet it is also growing dynamically, allowing E. coli to double in length every 20 minutes in rich medium. A bacterial virus must accomplish at least local degradation of the cell wall in order to cause cell lysis and release of the progeny virus particles. The main strategy for cell lysis, and indeed, the strategy employed by all double-stranded DNA bacteriophages, is to synthesize an enzyme, generically called an endolysin, which can degrade the peptidoglycan. The essential point is that the enzyme must not only get out of the cell to attack the cell wall but also do so at the proper time; i.e., when there have been sufficient numbers of progeny virions assembled in the infected cell. We work on a remarkable class of small membrane proteins which we have called 'holins', because they form 'holes' in the cell membrane to let out the endolysin. More than 60 different holins have been identified by scanning the genomes of different bacteriophages. We are focusing on the molecular properties of these proteins which permit them form holes in the membrane and also, perhaps even more importantly, on the 'clock' which allows the proteins to form the holes at the precisely correct time. In collaboration with Mike Manson of Biology, our lab showed that the holins accumulate utterly harmlessly in the membrane until they suddenly "trigger" to disrupt the membrane and kill the cell. A few seconds later, the cell explodes because the endolysins have been released and attacked the cell wall. A movie showing this can be seen if you visit the Young lab website: http://cowboy.tamu.edu/~younglab/ Another way to achieve lysis is to subvert the delicate biochemical pathways by which cell walls grow and form separations between progeny cells. We have discovered that, unlike dsDNA phages, small ssRNA and ssDNA bacteriophages, which have only room for 3 - 10 genes, synthesize a protein called an 'amurin' that inhibits a specific step in cell wall synthesis. As a result, just as if the cell wall synthesis had been blocked by a chemical antibiotic like penicillin, when the cell tries to divide and make a new cell wall between the daughter cells, it fails and lyses. This discovery may lead to a completely new class of antibiotics that mimic the molecular action of the amurins. Our lab is also interested in phage genomics and in applications of phage biology to antibacterial therapy, prophylaxis and diagnosis. Please visit the lab web page for information on these efforts. |
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| Selected Publications | |
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Selected Publications list Markov, D., Christie, G., Sauer, B., Calendar, R., Park, T., Young, R., and Severinov, K. (2004) P2 growth restriction on an rpoC mutant is suppressed by alleles of the Rz1 homolog lysC. J. Bacteriol. 186:4628-4637. Deaton, J., Savva, C. G., Sun, J., Holzenburg, A., Berry, J. and Young, R. (2004) Solubilization and delivery by GroEL of megadalton complexes of the lambda holin. Protein Science 13, 1778-1786. Summer, E., Carlos F. Gonzalez, C.F., Carlisle, T., Mebane, L.M., Cass, A. M. , Savva, C. G. , LiPuma, J. J. and Young, R. (2004) Burkholderia cenocepacia phage BcepMu and a family of Mu-like phages encoding potential pathogenesis factors. J. Molec. Biol. 340, 49 - 65. Xu, M., Struck, D. K., Deaton, J., Wang, I.-N and Young, R.. (2004) The signal arrest-release (SAR) sequence mediates export and control of the phage P1 endolysin. Proc. Nat. Acad. Sci. USA, 101:6415 - 6420. Deaton, J.D. Savva, C. G., Sun, J., Holzenburg, A. H. and Young, R. (2004) Functional bacteriorhodopsin is efficiently solubilized and delivered to membranes by the chaperonin GroEL. Proc. Nat. Acad. Sci. USA 101: 2281-2286. Wang, I.-N., Deaton, J.D. and Young, R. (2003) Sizing the holin lesion with an endolysin-b-galactosidase fusion. J. Bacteriol.185: 779-787. Bläsi, U., P. Fraisl, C.-Y. Chang, N. Zhang, and R. Young. 1999. The C-Terminal Sequence of the l Holin Constitutes a Cytoplasmic Regulatory Domain. J. Bacteriol. 181:2922-2929. Barenboim, M., C.-Y. Chang, F. dib Hajj, and R. Young. 1999. Characterization of the Dual Start Motif of a Class II Holin Gene. Molec. Microbiol. 32:715-728. Smith, D.L. and R. Young. 1998. Oligohistidine Tag Mutagenesis of the l Holin Gene. J. Bacteriol. 180:4199-4211. Smith, D.L., C.-Y. Chang, and R. Young. 1998. The l holin accumulates beyond the lethal triggering concentration under hyper-expression conditions. Gene Expression 7:39-52. Smith, D.L., D.K. Struck, J.M. Scholtz, and R. Young. 1998. Purification and biochemical characterization of the lambda holin. J. Bacteriol. 180:2531-2540. |
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