On August 9-10, 2023, a workshop was convened at the Pacific Northwest National Laboratory (PNNL) in Richland, WA that brought together a group of internationally recognized experts in metabolomics, natural products discovery, chemical ecology, chemical and biological threat assessment, cheminformatics, computational chemistry, cloud computing, artificial intelligence, and novel technology development. These experts were invited to assess the value and feasibility of a grand-scale project to create new technologies that would allow the identification and quantification of all small molecules, or to decode the molecular universe. The Decoding the Molecular Universe project would extend and complement the success of the Human Genome Project by developing new capabilities and technologies to measure small molecules (defined as non-protein, non-polymer molecules less than 1500 Daltons) of any origin and generated in biological systems or produced abiotically. Workshop attendees 1) explored what new understanding of biological and environmental systems could be revealed through the lens of small molecules; 2) characterized the similarities in current needs and technical challenges between each science or mission area for unambiguous and comprehensive determination of the composition and quantities of small molecules of any sample; 3) determined the extent to which technologies or methods currently exist for unambiguously and comprehensively determining the small molecule composition of any sample and in a reasonable time; and 4) identified the attributes of the ideal technology or approach for universal small molecule measurement and identification. The workshop concluded with a discussion of how a project of this scale could be undertaken, possible thrusts for the project, early proof-of-principle applications, and similar efforts upon which the project could be modeled.

Abstract The genomes of 46 archaeal species have been fully sequenced and published. As of this writing (September, 2007), 60 more are in various stages of progress. Analyses of these genomes are providing many useful insights into the evolution and functioning of diverse archaea, helping to understand the diverse physiological properties of archaea and their relationships to bacteria and eukarya.

Click to increase image sizeClick to decrease image size The views expressed in this commentary are those of the author and should not be taken as representing the Office of Biological and Environmental Research, the Office of Science, or the Department of Energy.

OMICS: A Journal of Integrative BiologyVol. 6, No. 1 MinireviewThe Department of Energy Microbial Cell Project: A 180° Paradigm Shift for BiologyDaniel DrellDaniel DrellSearch for more papers by this authorPublished Online:8 Jul 2004https://doi.org/10.1089/15362310252780799AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byBioinformatics and Its Application Areas1 October 2021lumpGEM: Systematic generation of subnetworks and elementally balanced lumped reactions for the biosynthesis of target metabolites20 July 2017 | PLOS Computational Biology, Vol. 13, No. 7Phenomics9 April 2014Cyanobacterial postgenomic research and systems biologyTrends in Biotechnology, Vol. 21, No. 11Description and Interpretation of Adaptive Evolution of Escherichia coli K-12 MG1655 by Using a Genome-Scale In Silico Metabolic ModelJournal of Bacteriology, Vol. 185, No. 21Initial Proteome Analysis of Model Microorganism Haemophilus influenzae Strain Rd KW20Journal of Bacteriology, Vol. 185, No. 15Thirteen Years of Building Constraint-Based In Silico Models of Escherichia coliJournal of Bacteriology, Vol. 185, No. 9Genome-scale microbial in silico models: the constraints-based approachTrends in Biotechnology, Vol. 21, No. 4Analysis of Metabolic Capabilities Using Singular Value Decomposition of Extreme Pathway MatricesBiophysical Journal, Vol. 84, No. 2Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growthNature, Vol. 420, No. 6912 Volume 6Issue 1Jan 2002 To cite this article:Daniel Drell.The Department of Energy Microbial Cell Project: A 180° Paradigm Shift for Biology.OMICS: A Journal of Integrative Biology.Jan 2002.3-9.http://doi.org/10.1089/15362310252780799Published in Volume: 6 Issue 1: July 8, 2004PDF download

Rats and rabbits immunized with porcine zonae pellucidae (ZP) develop antibodies to specific ZP proteins. The proteins recognized by rabbit and rat antibodies were identified using immunoblot procedures. For these studies, proteins were separated by high-resolution, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Proteins were transferred electrophoretically to nitrocellulose paper and antibody binding determined using 125I-labeled Staphylococcus aureus protein A (Staph A). The three major porcine ZP glycoprotein families were recognized by antibodies in the sera of both rabbits and rats. These antibodies were further characterized using Staph A binding and enzyme-linked (ELISA) immunoassays. Rabbits immunized with porcine ZP developed antibodies which recognized the porcine ZP as well as rat ZP antigens. Rats immunized with porcine ZP produced antibodies which recognized porcine ZP antigens but did not react with rat ZP antigens. While antibodies to porcine ZP, detected by Staph A binding and ELISA assays, correlated with infertility in rabbits [Wood et al. (1981) Biol. Reprod. 25:439], rats having these antibodies could have normal offspring. Continued fertility in rats following immunization with porcine ZP may be due to the failure to induce autoantibodies which recognized self ZP antigenic determinants.

Experiments presented in this paper indicate that DBA/2J (H-2d) mice parabiosed for more than 100 days to the F1 hybrid between DBA/2J and C3H/HeJ (H-2k) contain in their serum an anti-H-2k antibody that is preferentially reactive with hematopoietic tissue and is also capable of killing C3H/HeJ colony-forming stem cells in vivo (CFU-S). These findings make the antibody a likely participant in the "takeover" reaction, in which DBA/2J red and white cells eventually replace the F1 hybrid blood system. With these observations used as a basis, 10(8) DBA/2J spleen cells were injected along with anti-H-2Kk (anti-host) monoclonal antibody into 10-wk-old (DBA/2J x C3H/HeJ)F1 hybrid hosts. The recipients had a high surivival rate and exhibited long-term chimerism. Unlike the situation in the parabionts, the DBA/2J lymphoid cells in the injection chimeras were found to be unresponsive to C3H/HeJ alloantigens. This could result from the continued presence of F1 hybrid stimulator cells, which are missing in the parabionts. The injection chimeras indicate that one can establish stable chimerism in adult mice without irradiation or metabolic poisoning.

Joining adult DBA/2J (H-2d) mice with adult (DBA/2J × C3H/HeJ)F1 (H-2d/H-2k) mice in parabiosis results in long-term survival of 44% of such pairs, the complete takeover of the F1 lymphoid and erythropoietic systems by parent type cells, and specific unresponsiveness toward C3H/HeJ skin grafts on the parental partner. In an adoptive transfer system measuring the killing of an 131I-iododeoxyuridine-labeled tumor that is H-2 compatible with C3H/HeJ, parabiont spleen cells show full reactivity upon sensitization to C3H/HeJ alloantigens and do not inhibit the sensitization of normal DBA/2J cells to C3H/HeJ. The adoptively transferred parabiont cells do not appear to be active unless reexposed to C3H/HeJ antigen. However, intact parabionts show accelerated tumor destruction in situ even when not deliberately restimulated with C3H/HeJ spleen cells. Parabiont serum gives accelerated tumor clearance on passive transfer. Parabiont serum also shows complement-dependent antibody titers in vitro of 1:10 to 1:20 against lymphoid target cell antigens coded for by genes in the interval from K to I-E of the H-2 complex. Most of this activity is sensitive to 2-mercaptoethanol. Although circulating antibody is present in the parabionts, F1 parabiont skin shows no delay in rejection by normal DBA/2J recipients.

Parabiosis of adult DBA/2J (H-2 d ) mice with adult (DBA/2J× CSH/HeJ)F1 (H-2 d /H-2 k ) mice results in survival beyond 100 days in 44% of such pairs, induction ofin situ unresponsiveness to C3H/HeJ skin, and the complete takeover of the erythroid system of the F1 by parental cells. However, in vitro responsiveness to C3H/HeJ cells remains. Dye exclusion cytotoxicity assays establish the absence ofF 1 lymphoid cells in the spleens and bone marrow of both partners. The parental takeover of the erythroid system of the F1 partner requires immune recognition of the hybrid's alloantigens, because this takeover is not seen with tolerant parental cells. PartialH-2 differences (on the C3H background) influence both survival and the takeover reaction when incorporated into parabioses with DBA/2J partners. When only theK andI subregions ofH-2 were targets of the parental response, 58% of parabionts survived, with complete parental hemopoietic takeover. When onlyH-2D was the target, 83% of parabionts survived, with incomplete hemopoietic takeover. Changing the non-H-2 background of the F1 target did not significantly affect survival or takeover, while substituting a differentH-2 d parental strain (BALB/c) eliminated survival altogether.