Low, David - University of California, Santa Barbara - Biomolecular Science and Engineering

个人简介

Bachelor of Science in biology from UC San Diego, Master's of Science in microbiology from San Diego State University, Ph.D. in cellular biochemistry from UC Irvine, Postdoctoral work at Stanford University in molecular microbiology in Stanley Falkow's laboratory. Professor for 13 years at the University of Utah Health Sciences Center before moving to UC Santa Barbara in 1998. Co-founder of Remedyne, 2000; Vice-Chair MCDB, 2004-2008.

研究领域

My primary research interest concerns cellular communication in the bacterial world. Specifically, my laboratory focuses on the biology and mechanisms involved in contact-dependent growth inhibition (CDI). We first reported this phenomenon in 2005, in which one bacterial cell touches another, injecting a small peptide effector/toxin called the CdiA-CT. The Hayes laboratory has discovered that CdiA-CTs have diverse activities including ribonucleases and deoxyribonucleases. We have shown that these systems are expressed by many bacterial species including important pathogens such as Salmonella and uropathogenic Escherichia coli. CDI systems may play important roles in intra-species competition and coordination of cellular activities via cell-to-cell contact. Our goal is to determine how these systems contribute to the lifestyle of bacteria and their mechanisms of action. Another interest of my laboratory is in mechanisms of epigenetic regulation, specifically DNA methylation patterns. We are working with Mustafa Khammash to develop a predictive model for the pyelonephritis-associated pili (Pap) epigenetic regulatory system.

近期论文

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Morse,R.P., Nikolakakis, K.C., Willett, J.L.E., Gerrick, E., Low, D.A., Hayes, C.S., and Goulding, C.W. Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems. Proc. Nat’l. Acad. Sci. in press Maloy, S. Hughes, K. Encyclopedia of Genetics Low, D.A., and van der Woude, M "Phase variation." Elsevier, Oxford, UK. in press. Lim, Y.W., Schmieder, R., Haynes, M., Furlan, M., Matthews, D., Whiteson, K., Poole, S., Hayes, C., Low, D., Maughan, H., Edwards, R., Conrad, D., and Rohwer, F. Mechanistic model of Rothia mucilaginosa adaptation toward persistence in the CF lung, based on a genome reconstructed from metagenomic data. PLoS One, in press. Cossart, P., Maloy S., eds. Host-Pathogen Interactions. Hayes, C. S., Koskiniemi, S., Ruhe, Z. C., Poole, S. J. and Low, D. A. “Mechanisms and biological roles of contact-dependent growth inhibition (CDI) Cold Spring Press, Cold Spring Harbor, NY in press Casadesus, J, Low, DA. (2013) Programmed Heterogeneity: Epigenetic Mechanisms in Bacteria. J Biol Chem. in press. Koskiniemi, S., Lamoureux, J.G., Nikolakakis, K.C., t’Kint de Roodenbeke, C., Kaplan, M., Low, D.A., Hayes, C.S. Rhs proteins from diverse bacteria mediate intercellular competition. Proc Natl Acad Sci U S A, 110:7032-7037. Ruhe ZC, Low DA, Hayes CS. Bacterial contact-dependent growth inhibition. Trends in Microbiology. 2013. Epub 2013/03/12. doi: 10.1016/j.tim.2013.02.003. PubMed PMID: 23473845. Webb JS, Nikolakakis KC, Willett JL, Aoki SK, Hayes CS, Low DA. (2013) Delivery of CdiA Nuclease Toxins into Target Cells during Contact-Dependent Growth Inhibition. PloS ONE. 2013;8:e57609. PMC3585180. Morse RP, Nikolakakis KC, Willett JL, Gerrick E, Low DA, Hayes CS, et al. (2012) Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems. Proc Natl Acad Sci U S A. 109:21480-21485. PMC3535622. Nikolakakis K, Amber S, Wilbur JS, Diner EJ, Aoki SK, Poole SJ, Tuanyok A, Keim PS, Peacock S, Hayes CS, Low DA (2012) The toxin/immunity network of Burkholderia pseudomallei contact-dependent growth inhibition (CDI) systems. Mol. Microbiol. 84: 516-529. Diner, E. J., Beck, C. M. , Webb, J. S. , Low, D. A. and Hayes, C. S. (2012) Identification of a target cell permissive factor required for contact-dependent growth inhibition (CDI) Genes Dev. 26, 515-525. Charkowski, A., Blanco, C., Condemine, G., Expert, D., Franza, T., Hayes, C., Hugouvieux-Cotte-Pattat, N., Lopez-Solanilla, E., Low, D., Moleleki, L., Pirhonen, M., Pitman, A., Perna, N., Reverchon, S., Rodriquez-Palenzueala, P., San Francisco, M., Toth, I., Tsuyuma, S., van der Walls, J., van derWolf, J., Van Gijsegem, F., Yang, C.-H., Yedidia, I. 2012. The Role of Secretion Systems and Small Molecules in Soft-Rot Enterobacteriaceae. Annual Review of Phytopathology (2012) 50:425-449 Holberger, L.E., Lamoureux, J., Garza-Sánchez, F., Low, D.A., Hayes, C.S. (2011) A novel family of polymorphic toxin-antitoxin proteins in Bacillus species. FEBS Letters 586: 132-136 Poole, S.J., Diner, E.J., Aoki, S.K., Braaten, B.A., t'Kint de Roodenbeke, C., Low, D.A., and Hayes, C.S. (2011). Identification of Functional Toxin/Immunity Genes Linked to Contact-Dependent Growth Inhibition (CDI) and Rearrangement Hotspot (Rhs) Systems. PLoS Genetics 7, e1002217. Aoki, S.K., Poole, S.J., Hayes, C.S., and Low, D.A. (2011). Toxin on a stick: Modular CDI toxin delivery systems play roles in bacterial competition. Virulence 2, 356-359. Aoki, S.K., and Low, D.A. (2011). Using genetic approaches to delineate the pathway of contact-dependent growth inhibition. The Lure of Bacterial Genetics, S. Maloy, K.T. Hughes, and J. Casadesus, eds. (Washington, D.C., ASM Press), pp. 173-184. Aoki, S. K., Diner, E. J., t’Kint de Roodenbeke, C., Burgess, B. R., Poole, S. J., Braaten, B. A., Jones, A. M., Webb, J. S., Hayes, C. S., Cotter, P. A., and D. A. Low (2010) A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria. Nature 468:439-442 (PMCID:3058911) Hayes, C. S., Aoki, S. K., and D. A. Low (2010) Bacterial contact-dependent delivery systems. Annual Review of Genetics 44:71-90 PMC Journal, in process Aoki, S.K., Webb, J.S., Braaten, B.A., and Low, D.A. (2009). Contact-dependent growth inhibition causes reversible metabolic downregulation in Escherichia coli. Journal of Bacteriology 191:1777-1786, PMC2648372. Hayes, C. S., and D. A. Low (2009) Signals of growth regulation in bacteria. Current Opinion in Microbiology 12:667-673 (PMCID:2789310) Aoki, S. K., J. C. Malinverni, K. Jacoby, B. Thomas, R. Pamma, B. N. Trinh, S. Remers, J. Webb, B. A. Braaten, T. J. Silhavy, and D. A. Low. (2008). Contact-dependent growth inhibition requires the essential outer membrane protein BamA (YaeT) as the receptor and the inner membrane transport protein AcrB. Molecular Microbiology 70:323-40, PMC2579741. Aoki, S.K., Pamma, R., Hernday, A. Bickham, J. Braaten,B.A., and Low, D.A. (2005) Contact-dependent inhibition of growth in Escherichia coli. Science 309:1245-1248 Hernday, A.D., Braaten, B.A. and Low, D.A. (2003) The mechanism by which DNA adenine methylase and PapI activate the Pap epigenetic switch. Molecular Cell 12:947-957. Heithoff, D.M., Sinsheimer, R.L., Low, D.A. and Mahan, M.J. (1999) An essential role for DNA adenine methylation in bacterial virulence. Science 284:967. Holberger, L.E., Lamoureux, J., Garza-Sánchez, F., Low, D.A., Hayes, C.S. 2011. A novel family of polymorphic toxin-antitoxin proteins in Bacillus species. FEBS Letters 586: 132-136 Maloy, S., Hughes, K.T., and Casadesus, J. eds. The Lure of Bacterial Genetics. ASM Press, Washington, D.C.