Eric Miller

Eric S. Miller

Associate Professor
Ph.D., Purdue University

RNA-Protein Interactions, Bacteriophage and Microbial Products

(919) 515-7922 (office)
(919) 515-7230 (lab)
(919) 515-7867 (fax)
esm@mbio.ncsu.edu

Some of our publications on MedLine - a PubMed search for MILLER ES and (phage or Aeromicrobium or keratinase)

Two book chapters

Miller, E.S., J.D. Karam and E. Spicer. 1994. Control of translation initiation: mRNA structures and protein repressors. In Molecular Biology of Bateriophage T4. J.D. Karam et al. (Eds.), pp. 193 - 205. ASM Press. Carlson, K. and E.S. Miller (Eds.) 1994. Experiments in T4 Genetics. In Molecular Biology of Bateriophage T4. J.D. Karam et al. (Eds.), pp. 421 - 483. ASM Press.
Visit the NC State "PhagePage"!

Research Description
Translational Control in Bacteriophage A major interest of our laboratory is understanding how proteins recognize and bind messenger RNA to control the translational yield of protein. Recognition of RNA by protein is essential for cellular processes including gene regulation, macromolecular assembly, nucleic acid replication, viral infection, and catalysis. We study the molecular biology of RNA recognition by RegA translational repressor proteins from bacteriophages related to T4. RegA binds RNA at the initiator AUG but, unlike many other RNA-binding proteins, it does not appear to use RNA structure to recognize the binding site. Bacteriophages less studied than T4 encode RegA proteins and variations in the protein have been observed that still afford RNA binding. In addition, methods of sequence randomization and selection are applied to the RNA and to the RNA-binding domain of the repressor protein. We have immobilized a histidine-tagged phage RB69 RegA protein and used the selection methods to isolate a high-affinity RNA ligand. Of course, large double-stranded DNA (~ 170 kbp) phages like T4 encode and carry-out a number of interesting macromolecular functions. While control of gene expression in these phages (which infect diverse bacteria) is of fundamental interest, the phage are also a rich source of enzymes used by molecular biologists.

Applications in Environmental Diagnostics and Microbial Products Methods for selecting nucleic acid ligands with high affinity to RNA-binding proteins have been adapted to therapeutics and diagnostics. L. Gold and colleagues at the University of Colorado thrust this approach into the molecular biology lexicon in the early 1990's; today, numerous companies and research groups exploit variations on "combinatorial chemistry" or "in vitro" evolution to derive products or to unravel cellular processes. In our lab, we are focusing on water and food safety by selecting ligands ("aptamers") for environmental diagnostics. Intact microorganisms present surface molecules that can bind specific ligands and light-up when appropriately configured with a reporter. Virions are the current environmental target of interest.

Microorganisms produce and secrete bioactive compounds such as enzymes and antibiotics. The diversity of microbial life on earth, and the corresponding diversity of genomic information, portends a period of rapid discovery of novel microbial products. In our laboratory, we are evaluating and manipulating serine proteases (primarily from Bacillus spp.) for enhanced degradation of keratin, a major constituent of feathers, wool and hair. Applications are in recycling poultry by-products into feed supplements (amino acids from hydrolyzed feathers) as well as in recycling waste products for environmental and water quality protection. These studies can potentially help our state's agricultural interests, and improve / restore our natural resources. These projects are currently funded by the USDA. Several years ago, we initiated molecular genetic studies of antimicrobials produced by the soil bacterium Aeromicrobium erythreum. Our efforts resulted in a taxonomic description of this bacterium, development of systems for genetic manipulation, and characterization of the rRNA methylase for erythromycin resistance. The biosynthesis of erythromycin (a macrolide antibiotic) and the protein bacteriocin "aeromicin" (discovered in this laboratory) are carried-out by A. erythreum. While the interest is still there, we are not currently funded for the Aeromicrobium projects.

Last updated August 25, 2000 by ESMiller
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