- Undergraduate Education
- A.B. Rice University (1968)
- Graduate Education
- Ph.D. University of Texas, Dallas (1975)
- Postdoc. Harvard Medical School (1975-78)
- Joined Texas A&M in 1978
The Molecules and Mechanisms of Bacteriophage Lysis
Most bacterial viruses (phages) cause lysis of their host cell to release the progeny virions. Large phages elaborate an enzyme (“endolysin”) to degrade the cell wall and also a small membrane protein (“holin”). The holin accumulates in the membrane and then, at a precisely scheduled time, suddenly forms a hole to allow release of endolysin through the cytoplasmic membrane to gain access to the wall. We use molecular genetics and biochemistry to study how this small protein is able to act as a molecular “clock” and punch holes in membranes. Small phages make single proteins which cause host lysis in a different way. This strategy is to target the host cell wall synthesis machinery; that is, the virus makes a “protein antibiotic” that causes lysis in the same way as antibiotics like penicillin by inhibiting an enzyme in the multi-step pathway of murein biosynthesis. Thus, when the infected cell tries to divide, it blows up, or lyses, because it can’t make the new cell wall between the daughter cells. Remarkably, each of three different, small phages blocks a different step in the pathway. These small lysis proteins are models for a completely new class of antibacterial antibiotics. Also, the E. coli SlyD protein is required for this mode of lysis in one case. SlyD is a member of an ubiquitous family of proteins related to human “immunophilins,” the targets of immune-suppression drugs. We study SlyD to learn about the role of this class of proteins in biology.
Cahill, J, Rajaure, M, O'Leary, C, Sloan, J, Marrufo, A, Holt, A et al.. Genetic Analysis of the Lambda Spanins Rz and Rz1: Identification of Functional Domains. G3 (Bethesda). 2017;7 (2):741-753.
Gorzelnik, KV, Cui, Z, Reed, CA, Jakana, J, Young, R, Zhang, J et al.. Asymmetric cryo-EM structure of the canonical Allolevivirus Qβ reveals a single maturation protein and the genomic ssRNA in situ. Proc. Natl. Acad. Sci. U.S.A. 2016;113 (41):11519-11524.
Chen, Y, Young, R. The Last r Locus Unveiled: T4 RIII Is a Cytoplasmic Antiholin. J. Bacteriol. 2016;198 (18):2448-57.
Guardia, A, Gulten, G, Fernandez, R, Gómez, J, Wang, F, Convery, M et al.. N-Benzyl-4-((heteroaryl)methyl)benzamides: A New Class of Direct NADH-Dependent 2-trans Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity. ChemMedChem. 2016;11 (7):687-701.
Fan, X, Duan, X, Tong, Y, Huang, Q, Zhou, M, Wang, H et al.. The Global Reciprocal Reprogramming between Mycobacteriophage SWU1 and Mycobacterium Reveals the Molecular Strategy of Subversion and Promotion of Phage Infection. Front Microbiol. 2016;7 :41.
Young, R, Gill, JJ. MICROBIOLOGY. Phage therapy redux--What is to be done? Science. 2015;350 (6265):1163-4.
Liu, M, Gill, JJ, Young, R, Summer, EJ. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge. Sci Rep. 2015;5 :13754.
Liu, M, Bischoff, KM, Gill, JJ, Mire-Criscione, MD, Berry, JD, Young, R et al.. Bacteriophage application restores ethanol fermentation characteristics disrupted by Lactobacillus fermentum. Biotechnol Biofuels. 2015;8 :132.
Das, M, Bhowmick, TS, Ahern, SJ, Young, R, Gonzalez, CF. Control of Pierce's Disease by Phage. PLoS ONE. 2015;10 (6):e0128902.
Rajaure, M, Berry, J, Kongari, R, Cahill, J, Young, R. Membrane fusion during phage lysis. Proc. Natl. Acad. Sci. U.S.A. 2015;112 (17):5497-502.