The primary goal of this proposal is to increase the pace of experimental determination of the function of large and high priority gene families in bacterial genomes. These genes can help elucidate the mechanisms of antibiotic resistance, provide new drug targets or improve our understanding of the human microbiome. Specifically, we propose to catalyze the formation of a consortium of experimental and computational biologists that would collaborate directly to test experimentally the predicted functions of high-priority genes of currently unknown function or specificity. Central to this effort would be the creation of a community web-based database (portal) which would allow computational and experimental scientists to communicate easily, assist experimentalists in identifying those high-priority genes for which there are the highest- quality computational predictions for their molecular function, and providing feedback to the computational biologists, since it remains true that the insights and experience of the dedicated biochemist can be essential in guiding the development of algorithmic sophistication. Experimental validations of gene function would be reported in a manuscript when successful, or as annotations in the prediction database when negative. Many existing groups, both large and small, have the relevant expertise and could contribute to the overall effort by performing the pertinent gene function determination studies. During the course of the project it is anticipated that at least 100 gene families will be identified and subjected to experimental tests, directly affecting the annotations of thousands of important genes. The initial project will fund 40 teams across the US, and will create more than 40 new jobs providing a significant economic stimulus. It will also stream-line and integrate the process of computational predictions and biochemical function validation leading to significant improvement in the cost of future work. In addition to direct benefits to microbial biology, infectious disease research and computational biology this public experiment in the form of a new social network might have long-term transformative implications for funding and other economic implications.

Public Health Relevance

This project will be important in providing fundamental knowledge to many aspects of infectious disease research. Unknown genes from several important pathogens such as Mycobacterium tuberculosis and Helicobacter pylori will be high priority targets as will genes in model organisms with orthologous genes that are widely distributed in both bacterial pathogens and higher organisms including humans. A key factor in deciding priorities will be the health implications of successful predictions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
High Impact Research and Research Infrastructure Programs (RC2)
Project #
1RC2GM092602-01
Application #
7855712
Study Section
Special Emphasis Panel (ZGM1-GDB-2 (BG))
Program Officer
Anderson, James J
Project Start
2009-09-30
Project End
2011-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$2,323,184
Indirect Cost
Name
Boston University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Granger, Brian R; Chang, Yi-Chien; Wang, Yan et al. (2016) Visualization of Metabolic Interaction Networks in Microbial Communities Using VisANT 5.0. PLoS Comput Biol 12:e1004875
Chang, Yi-Chien; Hu, Zhenjun; Rachlin, John et al. (2016) COMBREX-DB: an experiment centered database of protein function: knowledge, predictions and knowledge gaps. Nucleic Acids Res 44:D330-5
Salvi, Francesca; Agniswamy, Johnson; Yuan, Hongling et al. (2014) The combined structural and kinetic characterization of a bacterial nitronate monooxygenase from Pseudomonas aeruginosa PAO1 establishes NMO class I and II. J Biol Chem 289:23764-75
Lluch-Senar, Maria; Luong, Khai; LlorĂ©ns-Rico, VerĂ³nica et al. (2013) Comprehensive methylome characterization of Mycoplasma genitalium and Mycoplasma pneumoniae at single-base resolution. PLoS Genet 9:e1003191
Elkin, Sarah R; Kumar, Abhinav; Price, Carol W et al. (2013) A broad specificity nucleoside kinase from Thermoplasma acidophilum. Proteins 81:568-82
Choi, Han-Pil; Juarez, Silvia; Ciordia, Sergio et al. (2013) Biochemical Characterization of Hypothetical Proteins from Helicobacter pylori. PLoS One 8:e66605
Zhou, Jindan; Rudd, Kenneth E (2013) EcoGene 3.0. Nucleic Acids Res 41:D613-24
Chatterjee, Kunal; Blaby, Ian K; Thiaville, Patrick C et al. (2012) The archaeal COG1901/DUF358 SPOUT-methyltransferase members, together with pseudouridine synthase Pus10, catalyze the formation of 1-methylpseudouridine at position 54 of tRNA. RNA 18:421-33
Francis, Kevin; Nishino, Shirley F; Spain, Jim C et al. (2012) A novel activity for fungal nitronate monooxygenase: detoxification of the metabolic inhibitor propionate-3-nitronate. Arch Biochem Biophys 521:84-9
Rodionova, Irina A; Scott, David A; Grishin, Nick V et al. (2012) Tagaturonate-fructuronate epimerase UxaE, a novel enzyme in the hexuronate catabolic network in Thermotoga maritima. Environ Microbiol 14:2920-34

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