There are currently four main areas of research within my laboratory (Publications listed at bottom of page):
Microbial Genomics and Bioinformatics
My laboratory has contributed to the annotation and curation of several prokaryotic genome sequences. These analyses have provided a framework for both various genetic and biochemical experiments to examine metabolic and regulatory networks and development of tools for genomic sequence analysis, such as ProphageFinder.
Most recently, together with Clemson University and the University of Washington Genome Sequencing Center, the genome sequence of Methanosaeta concilii, the predominant methane producer on Earth was determined using support from the National Science Foundation. Comparative genomic sequence approaches has provided insight into the physiology of this metabolic specialist as well as a model for genome evolution in Methanosaeta.
Mixture of Methanosarcina (cocci) and Methanosaeta (rods) species.
Evolution of Metal-dependent Transcriptional Regulators
Analysis of archaeal genome sequences has revealed differential paralogous expansion of genes belonging to predicted helix-turn-helix transcriptional regulatory protein families in closely related species. A cross-disciplinary approach to understanding the evolution, structure and function of these proteins in Archaea has been initiated together with collaborators at DePauw University. In addition to cloning, expressing and purifying various helix-turn-helix proteins for biochemical and structural analyses, a web application (Prokaryotic InterGenic Exploration Database, PIGED ) has been generated to facilitate identification of putative binding sites for these proteins. The long range goal of this project is the integration of these predicted transcriptional regulators into cellular physiology and an understanding of transcriptional regulatory networks in Archaea
ArsR/CadC/SmtB-regulated metal detoxification systems are widespread among prokaryotes due to lateral gene transfer
SCFAs and Poly-hydroxyalkanoates Biosynthesis
Poly-hydroxyalkanoates (PHA) are microbial carbon storage biopolymers synthesized from building blocks of short chain fatty acids (SCFAs) such as acetate, butyrate, and valerate. PHAs as bioplastics have commerical appeal due to their biodegradability. The long term goal of our work is to generate strains of Rhodobacter sphaeroides capable of generating mixed SCFA polymers in a cost-effective manner with properties suitable for commerical use. Our current efforts involve characterization of enzymes (SCFA kinases) involved in the activation of SCFAs for possible generation of modified poly-hydroxybutyrate (PHB).
Carbon storage vesicles in Rhodobacter sphaeroides, containing PHB, are clearly evident in cells grown under both aerobic and anaerobic conditions
Evolution of Quaternary Structure in the DJ-1/PfpI Protein Family
Over 5000 homologues of the DJ-1/PfpI protein family can readily be identified among biological organisms. This family of proteins exhibit a wide range of activities including a redox-sensitive chaperone in humans to a peptidase in Archaea to general stress proteins or proteins of unknown function in assorted eukaryotes and bacteria. An interesting facet of this protein family regarding evolution of function is the role of quaternary structure evidenced in the numerous members of this family exhibiting discrete dimeric or trimeric structures. This project involves the development of a bioinformatics tool called Natural Enzyme Variant (NEV)-BLAST. that allows investigators to rapidly screen "signature" amino acid sub-sequences within related amino acid sequences and identify interesting variants for study. Use of this application has allowed the prediction of quaternary structures for uncharacterized DJ-1/PfpI variants, which are currently being biochemically characterized.
Despite exhibiting high structural similarity at a tertiary level, monomers of DJ-1/PfpI family proteins assemble in unique quaternary structures that influence their activity and function
Publications (since 2006)
Barber, R.D., L. Zhang, M. Harnack, C. Ingram-Smith, R. Kaul, M. V. Olson, and K. S.Smith. 2011. Complete genome sequence of Methanosaeta concilii, a specialist in aceticlastic methanogenesis. J. Bacteriol (Submitted)
Barber, R.D. 2009. Nanotechnology and Diagnostics in the Age of Omics. Int. J. Biomedical Engineering and Technology 2:92-103.
Barber, R. and J. Maiers. 2007. A “game” introduction to bioinformatics sequence analyses. American Biology Teacher 69(6):359-363.
M. Bose and R. D. Barber. 2006. Prophage Finder: a prophage loci prediction tool for prokaryotic genome sequences. In Silico Biol.6(3): 223-227.
M. Bose, D. J. Slick, M. J. Sarto, P. Murphy, D. Roberts, J. R. Roberts, and R. D. Barber. 2006. Identification of SmtB/ArsR cis elements and proteins in archaea using the Prokaryotic InterGenic Exploration Database (PIGED). Archaea 2(1): 39-49.
Images taken from:
http://comenius.susqu.edu/bi/202/archaea/euryarchaeota/METHANOBACTERIA/METHANOBACTERIA.htm
http://jb.asm.org/cgi/content/full/187/12/3909
http://www.pnl.gov/biology/programs/msd/rhodobacter.stm