Bruce Geller
Antisense antibiotics; bacterial vectors for vaccines
Research Interests:
Antisense antibiotics; bacterial vectors for vaccines
Office: 534 Nash Hall
Courses taught: MB 311, Molecular Microbiology Lab: A Writing Intensive Course; MB 312, Bacterial Physiology and Metabolism; MB 479/579, Food Biotechnology
Degrees: Ph.D. University of Utah
Research
Mucosal Vaccine Delivery. My lab is developin an oral vaccine for strep throat in collabora with a pharmaceutical company. we have expressed a conserved sequence of the M protein (CRR) on the suface of Lactococcus lactis. Mice vaccinated nasally with the engineered lactococcal strain develop CRR-specific sIgA and serum IgA responses. Moreover, the vaccinated mice are protected from an infectious challenge with the causative agent of strep throat, Streptococcus pyogenes.
Antisense Antibiotics. In collaboration with AVI BioPharma, we are developin an antisense antibiotic. Phosphorodiamidate morpholino oligomers (PMOs) are DNA mimics that inhibit expression of specific mRNA. They are synthesized using the four natural bases, with a base sequence different than DNA in the chemical structure that links the bases together. Ribose has been replaced with a mopholine group, and the phosphodiester is substituted with a phosphordiamidate. These alterations make the antisense molecule resistant to nucleases, which is required for in vivo therapeutics. PMOs targeted to essential genes of E. coli reduce viability about 505 in pur cultures and about 90% in infected mice. Efficacy is limited by penetration of the outer membrane. We have covalently coupled membrane-penetrating peptides to the end of PMOs and found that low micromolar concentrations of these conjugates reduce viability of E. coli by up to 7 orders of magnitude.
Bacteriophage Infections of Lactococcus. Bacteriophage infection of Lactococcus lactis, L. cremoris, and other commercially important strains of gram positive bacteria is a major problem in the dairy industry. we have cloned a gene (pip) that is the phage receptors for one of three main species of lactococcal phages. We have constructed pip null mutants of Lactococcus lactis and found that they are completely reisistant to all phages that use Pip as a receptor. Our goal is to provide genetically engineered receptors that would delay or prevent bacteriophage infection. Moreover, pip mutants grow normally and make excellent cheese.
Selected Publications
Pub Med
Tilley, L., B. Mellbye, S. E. Puckett, P. L. Iversen, and B. L. Geller. 2007. Antisense Phosphorodiamidate Morpholino Oligomer-Peptide Conjugate: Dose-Response in Mice Infected with Escherichia coli. J. Antimicrob. Chemother 59:66-73.
Tilley, L., O.S. Hine, J.A. Kellogg, J.N. Hassinger, D. Weller, P.L. Iversen, and B.L. Geller. 2006. Gene-Specific Effects of Antisense Phosphorodiamidate Morpholino Oligomer-Peptide Conjugates on Escherichia coli and Salmonella typhimurium in Pure Culture and in Tissue Culture. Antimicrob, Agents Chemother. 50: 2789-2796.
Geller, B.L., J. Deere, L. Tilley, and P.L. Iversen. 2005. Antisense phosphorodiamidate morpholino oligomer inhibits viability of Escherichia coli in pure culture and in mouse peritonitis. J. Antimicrob. Chemother. 55:983-988.
Deere, J., P. Iversen, and B.L. Geller. 2005 Antisense phosphorodiamidate morpholino oligomer length and target position effect on gene-specific inhibition in Escherichia coli. Antimicrob. Agents Chemother. 49:249-255.
Mannam, P., K.F. Jones, and B.L. Geller, 2004. Mucosal vaccine made from live, recombinant Lactococcus lactis protects mice agains pharyngeal infection with Streptococcus pyogenes. Infect. Immun. 72:3444-50.
Geller, B.L., J.D. Deere, D.A. Stein, A.D. Kroeker, H.M. Moulton, and P.L. Iversen. 2003. Inhibition of gene expression in Escherichia coli by antisense phophorodiamidate morpholino oligomers. Antimicrob. Agents Chemother. 47:3233-3239.