David Low

Biography

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.

Research

I spent the first 20 years of my career studying epigenetic regulation in bacteria. My laboratory first described methylation patterns in bacteria and showed that they regulate ON/OFF gene regulatory switches that control cell surface structures such as pili. In 2004 we discovered that bacteria can inject different toxic/effector molecules into each other via a process that I called “contact-dependent growth inhibition” or “CDI”. My lab has focused on studying this phenomenon for the past 15 years, partnering with Professor Chris Hayes’s laboratory. Together with the Hayes lab we have identified the pathways by which CdiA, a stick-like structure on the cell surface that mediates CDI, binds to targets, delivers toxins, and modulates cell physiology and growth. My current interest is in identifying all of the critical factors required by CDI+ cells to build the CdiB/CdiA toxin delivery device and intoxicate neighboring cells. I am also interested in leveraging our knowledge from studying CDI to developing new antimicrobials and phage therapy.

Selected Publications

Low, D.A., Baker, J.B., Koonce, W.C. and Cunningham, D.D. (1981). Released protease nexin regulates cellular binding, internalization and degradation of serine proteases. Proc. Nat'l. Acad. Sci. USA 78:2340.

Low, D.A., Scott, R.W., Baker, J.B. and Cunningham, D.D. (1982). Cells regulate their mitogenic response to thrombin through release of protease nexin. Nature 298:476.

Braaten, B.A., Nou, X., Kaltenbach, L.S. and Low, D.A. (1994). Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in Escherichia coli. Cell 76:577-588.

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.

Hernday, A.D., Braaten, B.A., Maduro, G., Engelberts, P. and Low, D.A. (2004). Regulation of the Pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp. Molecular Cell 16: 537-547

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

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)

Koskiniemi, S., Lamoureux, J.G., Nikolakakis, K.C., t’Kint de Roodenbeke, C., Kaplan, M., Low, D.A., Hayes, C.S. (2013) Rhs proteins from diverse bacteria mediate intercellular competition. Proc. Natl. Acad. Sci. U.S.A. 110:7032-7037.

Jones AM, Garza-Sanchez F, So J, Hayes CS, Low DA. (2017) Activation of contact-dependent antibacterial tRNase toxins by translation elongation factors. Proc Natl Acad Sci U S A. 114(10):E1951-E7. doi: 10.1073/pnas.1619273114.

Ruhe ZC, Subramanian P, Song K, Nguyen JY, Stevens TA, Low DA, Jensen GJ, Hayes CS. Programmed Secretion Arrest and Receptor-Triggered Toxin Export during Antibacterial Contact-Dependent Growth Inhibition . 2018 Cell, 175(4):921-33