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Alex Beliaev
Cell Signaling and Communications IRP Leader

Alexander Beliaev leads EMSL's Cell Signaling and Communication Integrated Research Platform. He is also the Synthetic Biology team leader for Pacific Northwest National Laboratory's Biological Sciences Division. His expertise and interests span systems microbiology, functional genomics, synthetic biology, and biotechnology.

Over the last two decades, Beliaev’s work has focused on predictive understanding of energy and materials conversion by microbes with emphasis on metabolic and regulatory controls guiding these processes. He has led and co-led multi-institutional projects focusing on the diversity of microbial metabolism: from extracellular electron transfer in chemolithotrophic bacteria to photosynthetic energy capture in oxygenic phototrophs. This work led to the discovery of the molecular basis of dissimilatory metal reduction by marine and subsurface microorganisms, as well as to development of a broad understanding of mechanisms by which cyanobacteria maximize energy conversion to achieve ultrahigh growth. His academic and educational accomplishments have also led to a joint appointment with the Centre for Agriculture and the Bioeconomy at the Queensland University of Technology, where he serves as a professor of biotechnology.

Today, Beliaev is exploring fundamental mechanisms and design principles that govern the functioning of multi-species systems. He is incorporating cutting-edge measurement technologies into systems and synthetic biology approaches, especially with respect to microbial community function and host-microbe interactions, to take knowledge from the laboratory to the field and translate it into industrial applications and partnerships with industry.

Research Interests

  • Functional genomics
  • Systems microbiology
  • Synthetic biology
  • Biotechnology

Education

  • Postdoctoral training in Microbial Functional Genomics, Oak Ridge National Laboratory, 1999-2002
  • PhD in Molecular Microbiology, University of Massachusetts Microbiology/Molecular Biology, 1999
  • BS in Microbiology, Moscow State University, 1992

Publications

2019

Bohutskyi P, RS McClure, EA Hill, WC Nelson, WB Chrisler, J Nunez, and RS Renslow, et al. 2019. "Metabolic effects of vitamin B12 on physiology, stress resistance, growth rate and biomass productivity of Cyanobacterium stanieri planktonic and biofilm cultures." Algal Research 42. PNNL-SA-136164. doi:10.1016/j.algal.2019.101580

2018

McClure RS, C Overall, EA Hill, MA Charania, HC Bernstein, JE McDermott, and AS Beliaev. 2018. "Species-specific transcriptomic network inference of interspecies interactions in microbial communities". The ISME J, 12 (8):2011-2023. doi: 10.1038/s41396-018-0145-6

Bohutskyi P, LA Kucek, EA Hill, GE Pinchuk, SG Mundree, and AS Beliaev. 2018. "Conversion of stranded waste-stream carbon and nutrients into value-added products via metabolically coupled binary heterotroph-photoautotroph system." Bioresource Technology 260. PNNL-SA-126703. doi:10.1016/j.biortech.2018.02.080

Song H, WC Nelson, J Lee, RC Taylor, CS Henry, AS Beliaev, and D Ramkrishna, et al. 2018. "Metabolic Network Modeling for Computer-Aided Design of Microbial Interactions." In Emerging Areas in Bioengineering, edited by HN Chang, et al. 793-801. Weinheim:Wiley-VCH Verlag GmbH & Co. PNNL-SA-115176. doi:10.1002/9783527803293.ch45

 

2017

Bernstein HC, RS McClure, V Thiel, NC Sadler, YM Kim, WB Chrisler, EA Hill, DA Bryant, MF Romine, JK Jansson, JK Fredrickson, and AS Beliaev. 2017. "Indirect interspecies regulation; transcriptional and physiological responses of a cyanobacterium to heterotrophic partnership." mSystems 2(2):Article No. e00181-16. doi:10.1128/mSystems.00181-16

Hill EA, WB Chrisler, AS Beliaev, and HC Bernstein. 2017. "A flexible microbial co-culture platform for simultaneous utilization of methane and carbon dioxide from gas feedstocks." Bioresource Technology 228:250-256. doi:10.1016/j.biortech.2016.12.111

2016

Lindemann SR, HC Bernstein, HS Song, JK Fredrickson, MW Fields, W Shou, D Johnson, and AS Beliaev. 2016. "Engineering Microbial Consortia for Controllable Outputs." The ISME Journal 10(2016):2077-2084. doi:10.1038/ismej.2016.26

Bernstein HC, RS McClure, EA Hill, LM Markillie, WB Chrisler, MF Romine, JE McDermott, MC Posewitz, DA Bryant, A Konopka, JK Fredrickson, and AS Beliaev. 2016. "Unlocking the Constraints of Cyanobacterial Productivity: Acclimations Enabling Ultrafast Growth." mBio 7(4):Article No. e00949-16. doi:10.1128/mBio.00949-16

McClure RS, CC Overall, JE McDermott, EA Hill, LM Markillie, LA McCue, RC Taylor, M Ludwig, DA Bryant, and AS Beliaev. 2016. "Network Analysis of Transcriptomics Expands Regulatory Landscapes in Synechococcus sp. PCC 7002." Nucleic Acids Research 44(18):8810-8825. doi:10.1093/nar/gkw737

Sadler NC, HC Bernstein, MR Melnicki, MA Charania, EA Hill, LN Anderson, ME Monroe, RD Smith, AS Beliaev, and AT Wright. 2016. "Dinitrogenase Driven Photobiological Hydrogen Production Combats Oxidative Stress in Cyanothece sp. ATCC 51142." Applied Environmental Microbiology 82(24):7227-7235. doi:10.1128/AEM.02098-16

Wei H, J Dai, M Xia, MF Romine, L Shi, AS Beliaev, JM Tiedje, KH Nealson, JK Fredrickson, J Zhou, and D Qiu. 2016. "Functional roles of CymA and NapC in reduction of nitrate and nitrite by Shewanella putrefaciens W3-18-1." Microbiology 162(6):930-941. doi:10.1099/mic.0.000285

2015

Bernstein HC, MA Charania, RS McClure, NC Sadler, MR Melnicki, EA Hill, LM Markillie, CD Nicora, AT Wright, MF Romine, and AS Beliaev. 2015. "Multi-omic Dynamics Associate Oxygenic Photosynthesis with Nitrogenase-mediated H2 production in Cyanothece sp. ATCC 51142." Scientific Reports 5:Article No. 16004. doi:10.1038/srep16004

Hwang C, A Copeland, S Lucas, A Lapidus, KW Barry, T Glavina del Rio, E Dalin, H Tice, S Pitluck, DR Sims, T Brettin, D Bruce, JC Detter, CF Han, J Schmutz, F Larimer, M Land, L Hauser, NC Kyrpides, A Lykidis, PM Richardson, AS Beliaev, RA Sanford, FE Loeffler, and MW Fields. 2015. "Complete genome sequence of Anaeromyxobacter sp. Fw109-5, an Anaerobic, Metal-Reducing Bacterium Isolated from a Contaminated Subsurface Environment." Journal of Bacteriology 3(1):Article No. e01449-14. doi:10.1128/genomeA.01449-14

Song HS, RS McClure, HC Bernstein, CC Overall, EA Hill, and AS Beliaev. 2015. "Integrated in silico analyses of regulatory and metabolic networks of Synechococcus sp. PCC 7002 reveal relationships between gene centrality and essentiality." Life 5(2):1127-1140. doi:10.3390/life5021127

2014

Ansong C, NC Sadler, EA Hill, MP Lewis, EM Zink, RD Smith, AS Beliaev, A Konopka, and AT Wright. 2014. "Characterization of protein redox dynamics induced during light-to-dark transitions and nutrient limitation in cyanobacteria." Frontiers in Microbiology 5:Article No. 325. doi:10.3389/fmicb.2014.00325

Beliaev AS, MF Romine, M Serres, HC Bernstein, BE Linggi, LM Markillie, NG Isern, WB Chrisler, LA Kucek, EA Hill, G Pinchuk, DA Bryant, HS Wiley, JK Fredrickson, and A Konopka. 2014. "Inference of Interactions in Cyanobacterial-Heterotrophic Co-Cultures via Transcriptome Sequencing." The ISME Journal 8(11):2243-2255. doi:10.1038/ismej.2014.69

Bernstein HC, A Konopka, MR Melnicki, EA Hill, LA Kucek, S Zhang, G Shen, DA Bryant, and AS Beliaev. 2014. "Effect of mono- and dichromatic light quality on growth rates and photosynthetic performance of Synechococcus sp. PCC 7002." Frontiers in Microbiology 5:Article No. 488. doi:10.3389/fmicb.2014.00488 

Davies FK, VH Work, AS Beliaev, and MC Posewitz. 2014. "Engineering limonene and bisabolene production in wild type and a glycogen-deficient mutant of Synechococcus sp. PCC 7002." Frontiers in Bioengineering and Biotechnology 2:Artcle No. 21. doi:10.3389/fbioe.2014.00021 

Sadler NC, MR Melnicki, MH Serres, ED Merkley, WB Chrisler, EA Hill, MF Romine, S Kim, EM Zink, S Datta, RD Smith, AS Beliaev, A Konopka, and AT Wright. 2014. "Live Cell Chemical Profiling of Temporal Redox Dynamics in a Photoautotrophic Cyanobacterium." ACS Chemical Biology 9(1):291-300. doi:10.1021/cb400769v

Song HS, WR Cannon, AS Beliaev, and A Konopka. 2014. "Mathematical Modeling of Microbial Community Dynamics: A Methodological Review." Processes 2(4):711-752. doi:10.3390/pr2040711

2013

Melnicki MR, GE Pinchuk, EA Hill, LA Kucek, S Stolyar, JK Fredrickson, A Konopka, and AS Beliaev. 2013. "Feedback-Controlled LED Photobioreactor for Photophysiological Studies of Cyanobacteria." Bioresource Technology 134:127-133. doi:10.1016/j.biortech.2013.01.079

Song HS, D Ramkrishna, GE Pinchuk, AS Beliaev, A Konopka, and JK Fredrickson. 2013. "Dynamic Modeling of Aerobic Growth of Shewanella oneidensis. Predicting Triauxic Growth, Flux Distributions and Energy Requirement for Growth." Metabolic Engineering 15:25-33. doi:10.1016/j.ymben.2012.08.004

Vu T, EA Hill, LA Kucek, A Konopka, AS Beliaev, and JL Reed. 2013. "Computational evaluation of Synechococcus sp. PCC 7002 metabolism for chemical production." Biotechnology Journal 8(5):619-630. doi:10.1002/biot.201200315

2012

Leuze M, TV Karpinets, MH Syed, AS Beliaev, and E Uberbacher. 2012. "Binding motifs in bacterial gene promoters modulate transcriptional effects of global regulators CRP and ArcA." Gene Regulation and Systems Biology 6:93-107. doi:10.4137/GRSB.S9357

Melnicki MR, GE Pinchuk, EA Hill, LA Kucek, JK Fredrickson, A Konopka, and AS Beliaev. 2012. "Sustained H2 Production Driven by Photosynthetic Water Splitting in a Unicellular Cyanobacterium." mBio 3(4):Article No. e00197-12. doi:10.1128/mBio.00197-12

Vu T, S Stolyar, GE Pinchuk, EA Hill, LA Kucek, RN Brown, MS Lipton, AL Osterman, JK Fredrickson, A Konopka, AS Beliaev, and JL Reed. 2012. "Genome-Scale Modeling of Light-Driven Reductant Partitioning and Carbon Fluxes in Diazotrophic Unicellular Cyanobacterium Cyanothece sp. ATCC 51142." PLoS Computational Biology 8(4):E1002460. doi:10.1371/journal.pcbi.1002460

Vu T, S Stolyar, GE Pinchuk, EA Hill, LA Kucek, RN Brown, MS Lipton, AL Osterman, JK Fredrickson, A Konopka, AS Beliaev, and JL Reed. 2012. "Genome-scale modeling of light-driven reductant partitioning and carbon fluxes in diazotrophic unicellular cyanobacterium Cyanothece sp. ATCC 51142." PLoS Computational Biology 8(4):e1002460. doi:10.1371/journal.pcbi.1002460

Work VH, AS Beliaev, A Konopka, and MC Posewitz. 2012. "Microbial hydrocarbons: back to the future." Biofuels 3(2):103-105. doi:10.4155/bfs.12.3

2011

Clarke TA, M Edwards, AJ Gates, A Hall, G White, J Bradley, CL Reardon, L Shi, AS Beliaev, MJ Marshall, Z Wang, N Watmough, JK Fredrickson, JM Zachara, JN Butt, and DJ Richardson. 2011. "Structure of a Bacterial Cell Surface Decaheme Electron Conduit." Proceedings of the National Academy of Sciences of the United States of America 108(23):9384-9389. doi:10.1073/pnas.1017200108

Pinchuk GE, OV Geydebrekht, EA Hill, JL Reed, A Konopka, AS Beliaev, and JK Fredrickson. 2011. "Pyruvate and Lactate Metabolism by Shewanella oneidensis MR-1 under Fermentation, Oxygen Limitation, and Fumarate Respiration Conditions." Applied and Environmental Microbiology 77(23):8234-8240. doi:10.1128/AEM.05382-11

Pinchuk GE, OV Geydebrekht, EA Hill, JL Reed, A Konopka, AS Beliaev, and JK Fredrickson. 2011. "Pyruvate and Lactate Metabolism by Shewanella oneidensis MR-1 under Fermentation, Oxygen Limitation, and Fumarate Respiration Conditions." Applied and Environmental Microbiology 77(23):8234-8240. doi:10.1128/AEM.05382-11

2010

Marshall MJ, AS Beliaev, and JK Fredrickson. 2010. "Microbiological Transformations of Radionuclides in the Subsurface." Chapter 4 in Environmental Microbiology, Second Edition, ed. R. Mitchell; J.-D. Gu, pp. 96-114. Wiley-Blackwell, Hoboken, NJ. 

Bouhenni R, GJ Vora, JC Biffinger, S Shirodkar, KL Brockman, R Ray, P Wu, BJ Johnson, EM Biddle, MJ Marshall, LA Fitzgerald, B Little, JK Fredrickson, AS Beliaev, BR Ringeisen, and D Saffarini. 2010. "The role of Shewanella oneidensis MR-1 outer surface structures in extracellular electron transfer." Electroanalysis 22(7-8):856-864. 

Pinchuk GE, EA Hill, OV Geydebrekht, J De Ingeniis, X Zhang, A Osterman, JH Scott, SB Reed, MF Romine, A Konopka, AS Beliaev, JK Fredrickson, and JL Reed. 2010. "Constraint-Based Model of Shewanella oneidensis MR-1 Metabolism: a Tool for Data Analysis and Hypothesis Generation." PLoS Computational Biology 6(6):Art. No. e1000822. doi:10.1371/journal.pcbi.1000822

Reardon CL, A Dohnalkova, P Nachimuthu, DW Kennedy, D Saffarini, BW Arey, L Shi, Z Wang, DA Moore, JS Mclean, DM Moyles, MJ Marshall, JM Zachara, JK Fredrickson, and AS Beliaev. 2010. "Role of Outer-Membrane Cytochromes MtrC and OmcA in the Biomineralization of Ferrihydrite by Shewanella oneidensis MR-1." Geobiology 8(1):56-68. doi:10.1111/j.1472-4669.2009.00226.x

2009

Marshall MJ, A Dohnalkova, DW Kennedy, AE Plymale, SH Thomas, FE Loffler, R Sanford, JM Zachara, JK Fredrickson, and AS Beliaev. 2009. "Electron donor-dependent radionuclide reduction and nanoparticle formation by Anaeromyxobacter dehalogenans strain 2CP-C." Environmental Microbiology 11(2):534-543. 

Pinchuk GE, DA Rodionov, C Yang, X Li, AL Osterman, E Dervyn, OV Geydebrekht, SB Reed, MF Romine, FR Collart, J Scott, JK Fredrickson, and AS Beliaev. 2009. "Genomic reconstruction of Shewanella oneidensis MR-1 metabolism reveals previously uncharacterized machinery for lactate utilization." Proceedings of the National Academy of Sciences of the United States of America 106(8):2874-2879. 

Charania M, K Brockman, Y Zhang, A Banerjee, G Pinchuk, JK Fredrickson, AS Beliaev, and D Saffarini. 2009. "Involvement of a Membrane-Bound Class III Adenylate Cyclase in Regulation of Anaerobic Respiration in Shewanella oneidensis MR-1." Journal of Bacteriology 191(13):4298-4306. doi:10.1128/JB.01829-08

Charania M, KL Brockman, Y Zhang, A Banerjee, GE Pinchuk, JK Fredrickson, AS Beliaev, and D Saffarini. 2009. "Involvement of a Membrane-Bound Class III Adenylate Cyclase in Regulation of Anaerobic Respiration in Shewanella oneidensis MR-1." Journal of Bacteriology 191(13):4298-4306. 

Hartshorne RS, CL Reardon, DE Ross, J Nuester, TA Clarke, AJ Gates, PC Mills, JK Fredrickson, JM Zachara, L Shi, AS Beliaev, MJ Marshall, M Tien, SL Brantley, JN Butt, and D Richardson. 2009. "Characterization of an electron conduit between bacteria and the extracellular environment." Proceedings of the National Academy of Sciences of the United States of America 106(52):22169-22174. doi:10.1073/pnas.0900086106

Turick CE, AS Beliaev, BA Zakrajsek, CL Reardon, DA Lowy, TE Poppy, A Maloney, and AA Ekechukwu. 2009. "The Role of 4-Hydroxyphenylpyruvate Dioxygenase in Enhancement of Solid-Phase Electron Transfer by Shewanella oneidensis MR-1." FEMS Microbiology Ecology 68(2):223-225. 

2008

Marshall MJ, AE Plymale, DW Kennedy, L Shi, Z Wang, SB Reed, A Dohnalkova, CJ Simonson, C Liu, D Saffarini, MF Romine, JM Zachara, AS Beliaev, and JK Fredrickson. 2008. "Hydrogenase- and Outer Membrane c-Type Cytochrome-Facilitated Reduction of Technetium(VII) by Shewanella oneidensis MR-1." Environmental Microbiology 10(1):125-136. doi:10.1111/j.1462-2920.2007.01438.x

Pinchuk GE, CG Ammons, DE Culley, SM Li, JS McLean, MF Romine, KH Nealson, JK Fredrickson, and AS Beliaev. 2008. "Utilization of DNA as a Sole Source of Phosphorus, Carbon, and Energy by Shewanella spp.: Ecological and Physiological Implications for Dissimilatory Metal Reduction." Applied and Environmental Microbiology 74(4):1198-1208. doi:10.1128/AEM.02026-07

Fredrickson JK, MF Romine, AS Beliaev, JM Auchutung, ME Driscoll, TS Gardner, KH Nealson, AL Osterman, GE Pinchuk, JL Reed, D Rodionov, JLM Rodrigues, D Saffarini, MH Serres, AM Spormann, IB Zhulin, and JM Tiedje. 2008. "Towards Environmental Systems Biology of Shewanella." Nature Reviews. Microbiology 6(8):592-603. doi:10.1038/nrmicro1947

Mclean JS, GE Pinchuk, OV Geydebrekht, CL Bilskis, BA Zakrajsek, EA Hill, D Saffarini, MF Romine, YA Gorby, JK Fredrickson, and AS Beliaev. 2008. "Oxygen-dependent autoaggregation in Shewanella oneidensis MR-1." Environmental Microbiology 10(7):1861-1876. doi:10.1111/j.1462-2920.2008.01608.x

Shi L, S Deng, MJ Marshall, Z Wang, DW Kennedy, A Dohnalkova, HM Mottaz, EA Hill, YA Gorby, AS Beliaev, DJ Richardson, JM Zachara, and JK Fredrickson. 2008. " Direct Involvement of Type II Secretion System in Extracellular Translocation of Shewanella Oneidensis Outer Membrane Cytochromes MtrC and OmcA." Journal of Bacteriology 190(15):5512-5516. doi:10.1128/JB.00514-08

2007

Bretschger O, A Obraztsova, CA Sturm, IS Chang, YA Gorby, SB Reed, DE Culley, CL Reardon, S Barua, MF Romine, J Zhou, AS Beliaev, R Bouhenni, D Saffarini, F Mansfeld, BH Kim, JK Fredrickson, and KH Nealson. 2007. "Current Production and Metal Oxide Reduction by Shewanella Oneidensis MR-1 Wild Type and Mutants." Applied and Environmental Microbiology 73(21):7003-7012. doi:10.1128/AEM.01087-07

Driscoll ME, MF Romine, FS Juhn, MH Serres, LA McCue, AS Beliaev, JK Fredrickson, and TS Gardner. 2007. "Identification of diverse carbon utilization pathways in Shewanella oneidensis MR-1 via expression profiling." Genome Informatics 18:287-298. 

Elias DA, F Yang, HM Mottaz, AS Beliaev, and MS Lipton. 2007. "Enrichment of Functional Redox Reactive Proteins and Identification by Mass Spectrometry Results in Several Terminal Fe(III)-reducing Candidate Proteins in Shewanella oneidensis MR-1." Journal of Microbiological Methods 68(2):367-375. 

2006

Marshall MJ, AS Beliaev, A Dohnalkova, DW Kennedy, L Shi, Z Wang, MI Boyanov, B Lai, KM Kemner, JS Mclean, SB Reed, DE Culley, VL Bailey, CJ Simonson, D Saffarini, MF Romine, JM Zachara, and JK Fredrickson. 2006. "c-Type Cytochrome-Dependent Formation of U(IV) Nanoparticles by Shewanella oneidensis ." PloS Biology 4(8):1324-1333. 

Shi L, B Chen, Z Wang, DA Elias, MU Mayer, YA Gorby, S Ni, BH Lower, DW Kennedy, DS Wunschel, HM Mottaz, MJ Marshall, EA Hill, AS Beliaev, JM Zachara, JK Fredrickson, and TC Squier. 2006. "Isolation of a High-Affinity Functional Protein Complex between OmcA and MtrC: Two Outer Membrane Decaheme c-type Cytochromes of Shewanella oneidensis MR-1 ." Journal of Bacteriology 188(13):4705-4714. doi:10.1128/JB.01966-05

2005

Beliaev AS, DM Klingeman, J Klappenbach, L Wu, MF Romine, JM Tiedje, KH Nealson, JK Fredrickson, and J Zhou. 2005. "Global Transcriptome Analysis of Shewanella oneidensis MR-1 Exposed to Different Terminal Electron Acceptors." Journal of Bacteriology 187(20):7138-7145. doi:10.1128/JB.187.20.7138-7145.2005

Elias DA, ME Monroe, MJ Marshall, MF Romine, AS Beliaev, JK Fredrickson, GA Anderson, RD Smith, and MS Lipton. 2005. "Global detection and characterization of hypothetical proteins in Shewanella oneidensis MR-1 using LC-MS based proteomics based proteomics." Proteomics 5(12):3120-3130. doi:10.1002/pmic.200401140

Kolker E, AF Picone, MY Galperin, MF Romine, R Higdon, KS Makarova, N Kolker, GA Anderson, X Qiu, KJ Auberry, G Babnigg, AS Beliaev, P Edlefsen, DA Elias, YA Gorby, T Holzman, J Klappenbach, K Konstantinidis, ML Land, MS Lipton, LA McCue, ME Monroe, L Pasa-Tolic, GE Pinchuk, SO Purvine, M Serres, S Tsapin, BA Zakrajsek, W Zhu, J Zhou, F Larimer, C Lawrence, M Riley, FR Collart, JR Yates, III, RD Smith, CS Giometti, K Nealson, JK Fredrickson, and JM Tiedje. 2005. "Global Profiling of Shewanella oneidensis MR-1: Expression of Hypothetical Genes and Improved functional annotations." Proceedings of the National Academy of Sciences of the United States of America 102(6):2099-2104. 

2004

Beliaev AS. 2004. "Mutagenesis as a functional genomics tool." In Microbial Functional Genomics, ed. J Zhou, DK Thompson, JM Tiedje, pp. 207-240. John Wiley & Sons, New York, NY. 

2003

Liu Y, J Zhou, MV Omelchenko, AS Beliaev, A Venkateswaran, J Stair, L Wu, DK Thompson, D Xu, IB Rogozin, E Gaidamakova, M Zhai, KS Makarova, EV Koonin, and MJ Daly. 2003. "Transcriptome dynamics of Deinococcus radiodurans recovering from ionizing radiation." Proceedings of the National Academy of Sciences of the United States of America 100(7):4191-4196. 

Saffarini D, R Schultz, and AS Beliaev. 2003. "Involvement of cyclic AMP (cAMP) and cAMP receptor protein in anaerobic respiration of Shewanella oneidensis." Journal of Bacteriology 185(12):3668-3671. 

Yost C, LJ Hauser, F Larimer, D Thompson, AS Beliaev, J Zhou, Y Xu, and D Xu. 2003. "A computational study of Shewanella oneidensis MR-1: Structural prediction and functional inference of hypothetical proteins." OMICS. A Journal of Integrative Biology 7(2):177-191.