Toward a predictive understanding of Earth’s microbiomes to address 21st century challenges

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in mBio 7 (2016): e00714-16, doi:10.1128/mBio.00714-16.Microorganisms have shaped our planet and its inhabitants for over 3.5 billion years. Humankind has had a profound influence on the biosphere, manifested as global climate and land use changes, and extensive urbanization in response to a growing population. The challenges we face to supply food, energy, and clean water while maintaining and improving the health of our population and ecosystems are significant. Given the extensive influence of microorganisms across our biosphere, we propose that a coordinated, cross-disciplinary effort is required to understand, predict, and harness microbiome function. From the parallelization of gene function testing to precision manipulation of genes, communities, and model ecosystems and development of novel analytical and simulation approaches, we outline strategies to move microbiome research into an era of causality. These efforts will improve prediction of ecosystem response and enable the development of new, responsible, microbiome-based solutions to significant challenges of our time.E.L.B. is supported by the Genomes-to-Watersheds Subsurface Biogeochemical Research Scientific Focus Area, and T.R.N. is supported by ENIGMA-Ecosystems and Networks Integrated with Genes and Molecular Assemblies (http://enigma.lbl.gov) Scientific Focus Area, funded by the U.S. Department of Energy (US DOE), Office of Science, Office of Biological and Environmental Research under contract no. DE-AC02- 05CH11231 to Lawrence Berkeley National Laboratory (LBNL). M.E.M. is also supported by the US DOE, Office of Science, Office of Biological and Environmental Research under contract no. DE-AC02-05CH11231. Z.G.C. is supported by National Science Foundation Integrative Organismal Systems grant #1355085, and by US DOE, Office of Biological and Environmental Research grant # DE-SC0008182 ER65389 from the Terrestrial Ecosystem Science Program. M.J.B. is supported by R01 DK 090989 from the NIH. T.J.D. is supported by the US DOE Office of Science’s Great Lakes Bioenergy Research Center, grant DE-FC02- 07ER64494. J.L.G. is supported by Alfred P. Sloan Foundation G 2-15-14023. R.K. is supported by grants from the NSF (DBI-1565057) and NIH (U01AI24316, U19AI113048, P01DK078669, 1U54DE023789, U01HG006537). K.S.P. is supported by grants from the NSF DMS- 1069303 and the Gordon & Betty Moore Foundation (#3300)

Effective killing of the human pathogen Candida albicans by a specific inhibitor of non-essential mitotic kinesin Kip1p

Kinesins from the bipolar (Kinesin-5) family are conserved in eukaryotic organisms and play critical roles during the earliest stages of mitosis to mediate spindle pole body separation and formation of a bipolar mitotic spindle. To date, genes encoding bipolar kinesins have been reported to be essential in all organisms studied. We report the characterization of CaKip1p, the sole member of this family in the human pathogenic yeast Candida albicans. C. albicans Kip1p appears to localize to the mitotic spindle and loss of CaKip1p function interferes with normal progression through mitosis. Inducible excision of CaKIP1 revealed phenotypes unique to C. albicans, including viable homozygous Cakip1 mutants and an aberrant spindle morphology in which multiple spindle poles accumulate in close proximity to each other. Expression of the C. albicans Kip1 motor domain in Escherichia coli produced a protein with microtubule-stimulated ATPase activity that was inhibited by an aminobenzothiazole (ABT) compound in an ATP-competitive fashion. This inhibition results in ‘rigor-like’, tight association with microtubules in vitro. Upon treatment of C. albicans cells with the ABT compound, cells were killed, and terminal phenotype analysis revealed an aberrant spindle morphology similar to that induced by loss of the CaKIP1 gene. The ABT compound discovered is the first example of a fungal spindle inhibitor targeted to a mitotic kinesin. Our results also show that the non-essential nature and implementation of the bipolar motor in C. albicans differs from that seen in other organisms, and suggest that inhibitors of a non-essential mitotic kinesin may offer promise as cidal agents for antifungal drug discovery

Understanding the U.S. Bioeconomy: A New Definition and Landscape

This article provides an overview of the U.S. bioeconomy, discussing how its definition has evolved and been formalized over time. The first attempts to conceptualize and define the U.S.bioeconomy began in the early 1990s. This was followed by a series of government and private efforts to develop methods to understand and evaluate it and to develop programs to promote it. These efforts culminated in the 2020 release of the National Academies of Science, Engineering, and Medicine (NASEM), Safeguarding the Bioeconomy report. The report recommended a formal definition of the U.S. bioeconomy, providing the rationale for that particular definition in the U.S. context. Formally adopting a comprehensive definition of the U.S. bioeconomy would enable the U.S. government to better assess the bioeconomy’s current state, to develop strategies to support its growth, and to promote strategies to safeguard it. Along with this recommendation, the NASEM Safeguarding report also discussed defining the “bioeconomy landscape,” which involves more precise determination and quantification of which economic activities are part of and external to the U.S. economy. Defining this landscape could guide metric development and data collection needed to track the bioeconomy’s growth, conduct economic assessments, and enable policy makers to keep abreast of advances that could potentially pose new national or economic security challenges. The report also includes an analysis of the broad range national bioeconomy strategies, identification of the four drivers of the U.S. bioeconomy, and the first of its kind, comprehensive estimate of the size and scope of the U.S. bioeconomy of USD 959B (valued in 2016 constant USD).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Effective killing of the human pathogen by a specific inhibitor of non-essential mitotic kinesin Kip1p-4

<p><b>Copyright information:</b></p><p>Taken from "Effective killing of the human pathogen by a specific inhibitor of non-essential mitotic kinesin Kip1p"</p><p></p><p>Molecular Microbiology 2007;65(2):347-362.</p><p>Published online 01 Jul 2007</p><p>PMCID:PMC1976386.</p><p>© 2007 Cytokinetics, Incorporated; Journal compilation © 2007 Blackwell Publishing Ltd</p

Effective killing of the human pathogen by a specific inhibitor of non-essential mitotic kinesin Kip1p-2

<p><b>Copyright information:</b></p><p>Taken from "Effective killing of the human pathogen by a specific inhibitor of non-essential mitotic kinesin Kip1p"</p><p></p><p>Molecular Microbiology 2007;65(2):347-362.</p><p>Published online 01 Jul 2007</p><p>PMCID:PMC1976386.</p><p>© 2007 Cytokinetics, Incorporated; Journal compilation © 2007 Blackwell Publishing Ltd</p

Effective killing of the human pathogen by a specific inhibitor of non-essential mitotic kinesin Kip1p-0

<p><b>Copyright information:</b></p><p>Taken from "Effective killing of the human pathogen by a specific inhibitor of non-essential mitotic kinesin Kip1p"</p><p></p><p>Molecular Microbiology 2007;65(2):347-362.</p><p>Published online 01 Jul 2007</p><p>PMCID:PMC1976386.</p><p>© 2007 Cytokinetics, Incorporated; Journal compilation © 2007 Blackwell Publishing Ltd</p