Abstract
Termites harbor an abundance and diversity of symbiotic microbes in their gut, which comprise all the three domains of life, Eucarya, Bacteria, and Archaea. One of the most prominent features of this microbiota is the cellular association of the gut flagellates with eubacteria and/or methanogenic archaea. The eubacterial and methanogenic symbionts are observed both inside and on the surface of the host flagellate cells. Recent technological advances in genomics have enabled researchers to predict the functions of these as-yet-uncultivable prokaryotic symbionts, in addition to their phylogenetic positions and specific localizations based on 16S rRNA analyses. Several complete and draft genome sequences of endo- and ectosymbionts of gut flagellates have shown consistency of their functions in spite of their taxonomic diversity.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abdul Rahman N, Parks DH, Willner DL, Engelberktson AL, Goffredi SK, Warnecke F, Scheffrahn RH, Hugenholtz P (2015) A molecular survey of Australian and North American termite genera indicates that vertical inheritance is the primary force shaping termite gut microbiomes. Microbiome 3:e5
Andrew BJ (1930) Method and rate of protozoan refaunation in the termite Termopsis angusticollis. Hagen Univ Calif (Berkeley) Publ Zool 33:449–470
Berchtold M, Chatzinotas A, Schönhuber W, Brune A, Amann R, Hahn D, König H (1999) Differential enumeration and in situ localization of microorganisms in the hindgut of the lower termite Mastotermes darwiniensis by hybridization with rRNA-targeted probes. Arch Microbiol 172:407–416
Boucias DG, Cai Y, Sun Y, Lietze VU, Sen R, Raychoudhury R, Scharf ME (2013) The hindgut lumen prokaryotic microbiota of the termite Reticulitermes flavipes and its responses to dietary lignocellulose composition. Mol Ecol 22:1836–1853
Brauman A, Kane MD, Labat M, Breznak JA (1992) Genesis of acetate and methane by gut bacteria of nutritionally diverse termites. Science 257:1384–1387
Brauman A, Dore J, Eggleton P, Bignell DE, Breznak JA, Kane MD (2001) Molecular phylogenetic profiling of prokaryotic communities in guts of termites with different feeding habits. FEMS Microbiol Ecol 35:27–36
Breznak JA (2000) Ecology of prokaryotic microbes in the guts of wood- and litter-feeding termites. In: Abe T, Bignell DE, Higashi M (eds) Termites: evolution, sociality, symbioses, ecology. Kluwer Academic Publishers, Dordrecht, pp 209–232
Breznak JA, Switzer JM (1986) Acetate synthesis from H2 plus CO2 by termite gut microbes. Appl Environ Microbiol 52:623–630
Brune A (2014) Symbiotic digestion of lignocellulose in termite guts. Nat Rev Microbiol 12:168–180
Brune A (2017) Ectosymbiotic Endomicrobia – a transition stage towards intracellular symbionts? Environ Microbiol Rep 9:474–476
Brune A (2018) Methanogens in the digestive tract of termites. In: Hackstein JHP (ed) Microbiology monographs: (Endo)symbiotic methanogenic archaea. Springer-Nature, Heidelberg
Brune A, Ohkuma M (2011) Role of the termite gut microbiota in symbiotic digestion. In: Bignell DE, Roisin Y, Lo N (eds) Biology of termites: a modern synthesis. Springer, New York, pp 413–438
Brune A, Stingl U (2006) Prokaryotic symbionts of termite gut flagellates: phylogenetic and metabolic implications of a tripartite symbiosis. Prog Mol Subcell Biol 41:39–60
Cleveland LR, Grimstone AV (1964) The fine structure of the flagellate Mixotricha paradoxa and its associated micro-organisms. Proc R Soc Lond B 159:668–686
Deevong P, Hattori M, Yamada A, Trakulnaleamsai S, Ohkuma M, Noparatnaraporn N, Kudo T (2004) Isolation and detection of methanogens from the gut of higher termites. Microbes Environ 19:221–226
Desai MS, Brune A (2012) Bacteroidales ectosymbionts of gut flagellates shape the nitrogen-fixing community in dry-wood termites. ISME J 6:1302–1313
Desai MS, Strassert JFH, Meuser K, Hertel H, Ikeda-Ohtsubo W, Radek R, Brune A (2010) Strict cospeciation of devescovinid flagellates and Bacteroidales ectosymbionts in the gut of dry-wood termites (Kalotermitidae). Environ Microbiol 12:2120–2132
Donovan SE, Purdy KJ, Kane MD, Eggleton P (2004) Comparison of Euryarchaea strains in the guts and food-soil of the soil-feeding termite Cubitermes fungifaber across different soil types. Appl Environ Microbiol 70:3884–3892
Ebert A, Brune A (1997) Hydrogen concentration profiles at the oxic-anoxic interface: a microsensor study of the hindgut of the wood-feeding lower termite Reticulitermes flavipes (Kollar). Appl Environ Microbiol 63:4039–4046
Fenchel T, Finlay BJ (2018) Free-living protozoa with endosymbiotic methanogens. In: Hackstein JHP (ed) Microbiology monographs: (Endo)symbiotic methanogenic archaea. Springer-Nature, Heidelberg
Friedrich MW, Schmitt-Wagner D, Lueders T, Brune A (2001) Axial differences in community structure of Crenarchaeota and Euryarchaeota in the highly compartmentalized gut of the soil-feeding termite Cubitermes orthognathus. Appl Environ Microbiol 67:4880–4890
Graber JR, Breznak JA (2004) Physiology and nutrition of Treponema primitia, an H2/CO2-acetogenic spirochete from termite hindguts. Appl Environ Microbiol 70:1307–1314
Graber JR, Leadbetter JR, Breznak JA (2004) Description of Treponema azotonutricium sp. nov. and Treponema primitia sp. nov., the first spirochetes isolated from termite guts. Appl Environ Microbiol 70:1315–1320
Hara K, Shinzato N, Oshima T, Yamagishi A (2004) Endosymbiotic Methanobrevibacter species living in symbiotic protists of the termite Reticulitermes speratus detected by fluorescent in situ hybridization. Microbes Environ 19:120–127
Hongoh Y (2010) Diversity and genomes of uncultured microbial symbionts in the termite gut. Biosci Biotechnol Biochem 74:1145–1151
Hongoh Y (2011) Toward the functional analysis of uncultivable, symbiotic microorganisms in the termite gut. Cell Mol Life Sci 68:1311–1325
Hongoh Y, Ohkuma M, Kudo T (2003) Molecular analysis of bacterial microbiota in the gut of the termite Reticulitermes speratus (Isoptera; Rhinotermitidae). FEMS Microbiol Ecol 44:231–242
Hongoh Y, Deevong P, Inoue T, Moriya S, Trakulnaleamsai S, Ohkuma M, Vongkaluang C, Noparatnaraporn N, Kudo T (2005) Intra- and interspecific comparisons of bacterial diversity and community structure support coevolution of gut microbiota and termite host. Appl Environ Microbiol 71:6590–6599
Hongoh Y, Sato T, Dolan MF, Noda S, Ui S, Kudo T, Ohkuma M (2007a) The motility symbiont of the termite gut flagellate Caduceia versatilis is a member of the “Synergistes” group. Appl Environ Microbiol 73:6270–6276
Hongoh Y, Sato T, Noda S, Ui S, Kudo T, Ohkuma M (2007b) Candidatus Symbiothrix dinenymphae: bristle-like Bacteroidales ectosymbionts of termite gut protists. Environ Microbiol 9:2631–2635
Hongoh Y, Sharma VK, Prakash T, Noda S, Taylor TD, Kudo T, Sakaki Y, Toyoda A, Hattori M, Ohkuma M (2008a) Complete genome of the uncultured Termite Group 1 bacteria in a single host protist cell. Proc Natl Acad Sci USA 105:5555–5560
Hongoh Y, Sharma VK, Prakash T, Noda S, Toh H, Taylor TD, Kudo T, Sakaki Y, Toyoda A, Hattori M, Ohkuma M (2008b) Genome of an endosymbiont coupling N2 fixation to cellulolysis within protist cells in termite gut. Science 322:1108–1109
Ikeda-Ohtsubo W, Brune A (2009) Cospeciation of termite gut flagellates and their bacterial endosymbionts: Trichonympha species and ‘Candidatus Endomicrobium trichonymphae’. Mol Ecol 18:332–342
Ikeda-Ohtsubo W, Desai M, Stingl U, Brune A (2007) Phylogenetic diversity of ‘Endomicrobia’ and their specific affiliation with termite gut flagellates. Microbiology 153:3458–3465
Ikeda-Ohtsubo W, Faivre N, Brune A (2010) Putatively free-living ‘Endomicrobia’ – ancestors of the intracellular symbionts of termite gut flagellates? Environ Microbiol Rep 2:554–559
Ikeda-Ohtsubo W, Strassert JF, Kohler T, Mikaelyan A, Gregor I, McHardy AC, Tringe SG, Hugenholtz P, Radek R, Brune A (2016) ‘Candidatus Adiutrix intracellularis’, an endosymbiont of termite gut flagellates, is the first representative of a deep-branching clade of Deltaproteobacteria and a putative homoacetogen. Environ Microbiol 18:2548–2564
Inoue J, Saita K, Kudo T, Ui S, Ohkuma M (2007) Hydrogen production by termite gut protists: characterization of iron hydrogenases of parabasalian symbionts of the termite Coptotermes formosanus. Eukaryot Cell 6:1925–1932
Inoue J, Noda S, Hongoh Y, Ui S, Ohkuma M (2008) Identification of endosymbiotic methanogen and ectosymbiotic spirochetes of gut protists of the termite Coptotermes formosanus. Microbes Environ 23:94–97
Izawa K, Kuwahara H, Kihara K, Yuki M, Lo N, Itoh T, Ohkuma M, Hongoh Y (2016) Comparison of intracellular “Ca. Endomicrobium trichonymphae” genomovars illuminates the requirement and decay of defense systems against foreign DNA. Genome Biol Evol 8:3099–3107
Izawa K, Kuwahara H, Sugaya K, Lo N, Ohkuma M, Hongoh Y (2017) Discovery of ectosymbiotic Endomicrobium lineages associated with protists in the gut of stolotermitid termites. Environ Microbiol Rep 9:411–418
Jenkins TM, Dean RE, Verkerk R, Forschler BT (2001) Phylogenetic analyses of two mitochondrial genes and one nuclear intron region illuminate European subterranean termite (Isoptera: Rhinotermitidae) gene flow, taxonomy, and introduction dynamics. Mol Phylogenet Evol 20:286–293
Kirby H (1930) Trichomonad flagellates from termites. Univ Calif (Berkeley) Publ Zool 33:393–444
Kirby H (1944) The structural characteristics and nuclear parasites of some species of Trichonympha in termites. Univ Calif (Berkeley) Publ Zool 49:185–282
Kitade O (2004) Comparison of symbiotic flagellate faunae between termites and a wood-feeding cockroach of the genus Cryptocercus. Microbes Environ 19:215–220
Kitade O, Matsumoto T (1998) Characteristics of the symbiotic flagellate composition within the termite family Rhinotermitidae (Isoptera). Symbiosis 25:271–278
Kitade O, Maeyama T, Matsumoto T (1997) Establishment of symbiotic flagellate fauna of Hodotermopsis japonica (Isoptera: Termopsidae). Sociobiology 30:161–167
Kuwahara H, Yuki M, Izawa K, Ohkuma M, Hongoh Y (2017) Genome of ‘Ca. Desulfovibrio trichonymphae’, an H2-oxidizing bacterium in a tripartite symbiotic system within a protist cell in the termite gut. ISME J 11:766–776
Leadbetter JR, Breznak JA (1996) Physiological ecology of Methanobrevibacter cuticularis sp. nov. and Methanobrevibacter curvatus sp. nov., isolated from the hindgut of the termite Reticulitermes flavipes. Appl Environ Microbiol 62:3620–3631
Leadbetter JR, Crosby LD, Breznak JA (1998) Methanobrevibacter filiformis sp. nov., a filamentous methanogen from termite hindguts. Arch Microbiol 169:287–292
Leadbetter JR, Schmidt TM, Graber JR, Breznak JA (1999) Acetogenesis from H2 plus CO2 by spirochetes from termite guts. Science 283:686–689
Lee MJ, Schreurs PJ, Messer AC, Zinder SH (1987) Association of methanogenic bacteria with flagellated protozoa from a termite gut. Curr Microbiol 15:337–341
Lilburn TG, Kim KS, Ostrom NE, Byzek KR, Leadbetter JR, Breznak JA (2001) Nitrogen fixation by symbiotic and free-living spirochetes. Science 292:2495–2498
Messer AC, Lee MJ (1989) Effect of chemical treatments on methane emission by the hindgut microbiota in the termite Zootermopsis angusticollis. Microb Ecol 18:275–284
Mikaelyan A, Köhler T, Lampert N, Rohland J, Boga H, Meuser K, Brune A (2015) Classifying the bacterial gut microbiota of termites and cockroaches: a curated phylogenetic reference database (DictDb). Syst Appl Microbiol 38:472–482
Mikaelyan A, Thompson CL, Meuser K, Zheng H, Rani P, Plarre R, Brune A (2017) High-resolution phylogenetic analysis of Endomicrobia reveals multiple acquisitions of endosymbiotic lineages by termite gut flagellates. Environ Microbiol Rep 9:477–483
Müller N, Timmers P, Plugge CM, Stams AJM, Schink B (2018) Syntrophy in methanogenic degradation. In: Hackstein JHP (ed) Microbiology monographs: (Endo)symbiotic methanogenic archaea. Springer-Nature, Heidelberg
Noda S, Ohkuma M, Yamada A, Hongoh Y, Kudo T (2003) Phylogenetic position and in situ identification of ectosymbiotic spirochetes on protists in the termite gut. Appl Environ Microbiol 69:625–633
Noda S, Iida T, Kitade O, Nakajima H, Kudo T, Ohkuma M (2005) Endosymbiotic Bacteroidales bacteria of the flagellated protist Pseudotrichonympha grassii in the gut of the termite Coptotermes formosanus. Appl Environ Microbiol 71:8811–8817
Noda S, Inoue T, Hongoh Y, Kawai M, Nalepa CA, Vongkaluang C, Kudo T, Ohkuma M (2006a) Identification and characterization of ectosymbionts of distinct lineages in Bacteroidales attached to flagellated protists in the gut of termites and a wood-feeding cockroach. Environ Microbiol 8:11–20
Noda S, Kawai M, Nakajima H, Kudo T, Ohkuma M (2006b) Identification and in situ detection of two lineages of Bacteroidales ectosymbionts associated with a termite gut protist, Oxymonas sp. Microbes Environ 21:16–22
Noda S, Kitade O, Inoue T, Kawai M, Kanuka M, Hiroshima K, Hongoh Y, Constantino R, Uys V, Zhong J-H, Kudo T, Ohkuma M (2007) Cospeciation in the triplex symbiosis of termite gut protists (Pseudotrichonympha spp.), their hosts, and their bacterial endosymbionts. Mol Ecol 16:1257–1266
Noda S, Hongoh Y, Sato T, Ohkuma M (2009) Complex coevolutionary history of symbiotic Bacteroidales bacteria of various protists in the gut of termites. BMC Evol Biol 9:e158
Odelson DA, Breznak JA (1983) Volatile fatty acid production by the hindgut microbiota of xylophagous termites. Appl Environ Microbiol 45:1602–1613
Odelson DA, Breznak JA (1985a) Cellulase and other polymer-hydrolyzing activities of Trichomitopsis termopsidis, a symbiotic protozoan from termites. Appl Environ Microbiol 49:622–626
Odelson DA, Breznak JA (1985b) Nutrition and growth characteristics of Trichomitopsis termopsidis, a cellulolytic protozoan from termites. Appl Environ Microbiol 49:614–621
Ohkuma M (2008) Symbioses of flagellates and prokaryotes in the gut of lower termites. Trends Microbiol 16:345–352
Ohkuma M, Kudo T (1996) Phylogenetic diversity of the intestinal bacterial community in the termite Reticulitermes speratus. Appl Environ Microbiol 62:461–468
Ohkuma M, Noda S, Kudo T (1999) Phylogenetic relationships of symbiotic methanogens in diverse termites. FEMS Microbiol Lett 171:147–153
Ohkuma M, Sato T, Noda S, Ui S, Kudo T, Hongoh Y (2007) The candidate phylum ‘Termite Group 1’ of bacteria: phylogenetic diversity, distribution, and endosymbiont members of various gut flagellated protists. FEMS Microbiol Ecol 60:467–476
Ohkuma M, Noda S, Hattori S, Iida T, Yuki M, Starns D, Inoue J, Darby AC, Hongoh Y (2015) Acetogenesis from H2 plus CO2 and nitrogen fixation by an endosymbiotic spirochete of a termite-gut cellulolytic protist. Proc Natl Acad Sci USA 112:10224–10230
Pester M, Brune A (2007) Hydrogen is the central free intermediate during lignocellulose degradation by termite gut symbionts. ISME J 1:551–565
Pester M, Tholen A, Friedrich MW, Brune A (2007) Methane oxidation in termite hindguts: absence of evidence and evidence of absence. Appl Environ Microbiol 73:2024–2028
Radek R (1999) Flagellates, bacteria, and fungi associated with termites: diversity and function in nutrition – a review. Ecotropica 5:183–196
Radek R, Tischendorf G (1999) Bacterial adhesion to different termite flagellates: ultrastructural and functional evidence for distinct molecular attachment modes. Protoplasma 207:43–53
Radek R, Roesel J, Hausmann K (1996) Light and electron microscopic study of the bacterial adhesion to termite flagellates applying lectin cytochemistry. Protoplasma 193:105–122
Ramos AR, Grein F, Oliveira GP, Venceslau SS, Keller KL, Wall JD, Pereira IA (2015) The FlxABCD-HdrABC proteins correspond to a novel NADH dehydrogenase/heterodisulfide reductase widespread in anaerobic bacteria and involved in ethanol metabolism in Desulfovibrio vulgaris Hildenborough. Environ Microbiol 17:2288–2305
Sato T, Hongoh Y, Noda S, Hattori S, Ui S, Ohkuma M (2009) Candidatus Desulfovibrio trichonymphae, a novel intracellular symbiont of the flagellate Trichonympha agilis in termite gut. Environ Microbiol 11:1007–1015
Sato T, Kuwahara H, Fujita K, Noda S, Kihara K, Yamada A, Ohkuma M, Hongoh Y (2014) Intranuclear verrucomicrobial symbionts and evidence of lateral gene transfer to the host protist in the termite gut. ISME J 8:1008–1019
Shinzato N, Matsumoto T, Yamaoka I, Oshima T, Yamagishi A (1999) Phylogenetic diversity of symbiotic methanogens living in the hindgut of the lower termite Reticulitermes speratus analyzed by PCR and in situ hybridization. Appl Environ Microbiol 65:837–840
Stingl U, Maass A, Radek R, Brune A (2004) Symbionts of the gut flagellate Staurojoenina sp. from Neotermes cubanus represent a novel, termite-associated lineage of Bacteroidales: description of ‘Candidatus Vestibaculum illigatum’. Microbiology 150:2229–2235
Stingl U, Radek R, Yang H, Brune A (2005) “Endomicrobia”: cytoplasmic symbionts of termite gut protozoa form a separate phylum of prokaryotes. Appl Environ Microbiol 71:1473–1479
Strassert JFH, Köhler T, Wienemann THG, Ikeda-Ohtsubo W, Faivre N, Franckenberg S, Plarre R, Radek R, Brune A (2012) ‘Candidatus Ancillula trichonymphae’, a novel lineage of endosymbiotic Actinobacteria in termite gut flagellates of the genus Trichonympha. Environ Microbiol 14:3259–3270
Strassert JF, Mikaelyan A, Woyke T, Brune A (2016) Genome analysis of ‘Candidatus Ancillula trichonymphae’, first representative of a deep-branching clade of Bifidobacteriales, strengthens evidence for convergent evolution in flagellate endosymbionts. Environ Microbiol Rep. doi:https://doi.org/10.1111/1758-2229.12451
Sugimoto A, Inoue T, Tayasu I, Miller LR, Takeichi S, Abe T (1998) Methane and hydrogen production in a termite-symbiont system. Ecol Res 13:241–257
Sugimoto A, Bignell DE, Macdonald J (2000) Global impact of termites on the carbon cycle. In: Abe T, Bignell DE, Higashi M (eds) Termites: evolution, sociality, symbioses, ecology. Kluwer Academic, Dordrecht, pp 409–436
Tai V, James ER, Nalepa CA, Scheffrahn RH, Perlman SJ, Keeling PJ (2015) The role of host phylogeny varies in shaping microbial diversity in the hindguts of lower termites. Appl Environ Microbiol 81:1059–1070
Tai V, Carpenter KJ, Weber PK, Nalepa CA, Perlman SJ, Keeling PJ (2016) Genome evolution and nitrogen fixation in bacterial ectosymbionts of a protist inhabiting wood-feeding cockroaches. Appl Environ Microbiol 82:4682–4695
Tamm SL (1980) The ultrastructure of prokaryotic-eukaryotic cell junctions. J Cell Sci 44:335–352
Tamm SL (1982) Flagellated ectosymbiotic bacteria propel a eukaryotic cell. J Cell Biol 94:697–709
Tholen A, Brune A (2000) Impact of oxygen on metabolic fluxes and in situ rates of reductive acetogenesis in the hindgut of the wood-feeding termite Reticulitermes flavipes. Environ Microbiol 2:436–449
Tokura M, Ohkuma M, Kudo T (2000) Molecular phylogeny of methanogens associated with flagellated protists in the gut and with the gut epithelium of termites. FEMS Microbiol Ecol 33:233–240
Tsunoda K, Ohmura W, Yoshimura T, Tokoro M (1993) Methane emission by the termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae) I. Effects of termite caste, population size and volume of test containers. Wood Res 79:34–40
Wenzel M, Radek R, Brugerolle G, König H (2003) Identification of the ectosymbiotic bacteria of Mixotricha paradoxa involved in movement symbiosis. Eur J Protistol 39:11–23
Yamin MA (1978) Axenic cultivation of the cellulolytic flagellate Trichomitopsis termopsidis (Cleveland) from the termite Zootermopsis. J Protozool 25:535–538
Yamin MA (1979) Flagellates of the orders Trichomonadida Kirby, Oxymonadida Grassé, and Hypermastigida Grassi and Foà reported from lower termites (Isoptera families Mastotermitidae, Kalotermitidae, Hodotermitidae, Termopsidae, Rhinotermitidae, and Serritermitidae) and from the wood-feeding roach Cryptocercus (Dictyoptera: Cryptocercidae). Sociobiology 4:1–120
Yamin MA (1980) Cellulose metabolism by the termite flagellate Trichomitopsis termopsidis. Appl Environ Microbiol 39:859–863
Yamin MA (1981) Cellulose metabolism by the flagellate Trichonympha from a termite is independent of endosymbiotic bacteria. Science 211:58–59
Yoshimura T (1995) Contribution of the protozoan fauna to nutritional physiology of the lower termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae). Wood Res 82:68–129
Yuki M, Kuwahara H, Shintani M, Izawa K, Sato T, Starns D, Hongoh Y, Ohkuma M (2015) Dominant ectosymbiotic bacteria of cellulolytic protists in the termite gut also have the potential to digest lignocellulose. Environ Microbiol 17:4942–4953
Zheng H, Dietrich C, Thompson CL, Meuser K, Brune A (2015) Population structure of Endomicrobia in single host cells of termite gut flagellates (Trichonympha spp.). Microbes Environ 30:92–98
Zheng H, Dietrich C, Radek R, Brune A (2016) Endomicrobium proavitum, the first isolate of Endomicrobia class. nov. (phylum Elusimicrobia) – an ultramicrobacterium with an unusual cell cycle that fixes nitrogen with a Group IV nitrogenase. Environ Microbiol 18:191–204
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Hongoh, Y., Ohkuma, M. (2018). Termite Gut Flagellates and Their Methanogenic and Eubacterial Symbionts. In: Hackstein, J. (eds) (Endo)symbiotic Methanogenic Archaea. Microbiology Monographs, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-319-98836-8_5
Download citation
DOI: https://doi.org/10.1007/978-3-319-98836-8_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-98835-1
Online ISBN: 978-3-319-98836-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)