Environmental microbiology, host-microbe interactions, inflammatory bowel disease, human microbiome
My research uses sequencing and computational biology approaches to understand the composition and metabolism of microbial communities, both in the context of human health and in other environments, such as the rare biosphere. High-throughput sequencing lets us study the microbial communities of many environments in high resolution, as well as understanding how these communities change and interact with their environments over time. However, only by applying appropriate quantitative methods to microbial community analysis can we both understand basic biology and translational potential. In the context of human health, the genetic potential of the 1-2 kg of microbiota resident in the gut is vastly greater than that of their human hosts; it is critical to understand both how these microbiota interact with their hosts over time and in response to stimuli, and the translational potential of these discoveries. From studying the rare biosphere, we will continue to learn novel microbial biochemistry, strategies for environmental adaptation, and potentially novel therapeutics.
The average adult gut contains tenfold more bacteria than cells in the human body, which collectively encode an order of magnitude more genes than the human genome. The composition of these microbes varies dramatically between individuals and over time. The gut microbiome has long been linked with inflammatory bowel disease, and many studies have linked Crohn’s disease to specific structural changes in the microbiota, including decreased microbial diversity, decreased abundance of clades IV and XIVa Clostridia, and increased Enterobacteriaceae. While microbial community function in healthy individuals is typically much more stable than community composition, it is more perturbed than composition in IBD patients (Morgan et al, 2012), indicating that the same community functions are disrupted despite individual variation in the specific taxa that perform these functions. However, these microbial signatures are much less prominent in new-onset IBD (Gevers et al, 2014). It is therefore unclear whether microbial IBD signatures are reflective of causation, or of long-term community adaptation to chronic redox stress or medication use. To answer these questions, I am interested in collecting longitudinal data, both clinical and from model organisms, to study the relationship between host and microbiota in inflammatory bowel disease over time. I am most interested in modeling how the composition and function of the microbiota fluctuates between flares and remission, and how it is systematically altered by factors such as the use of host medication. Understanding both these questions in greater detail will greatly improve our understanding of the microbiota as a potential therapeutic target in the context of disease.
Collaborators: Dr Curtis Huttenhower, Harvard T.H. Chan School of Public Health, Dr. Andrew Day, University of Otago at Christchurch
Chthonomonas calidirosea strain T49T was the first cultured representative of the phylum Armatimonadetes (formerly candidate division OP10), as well as the first sequenced Armatimonadetes genome (Lee et al, 2014). C. calidirosea is found at very low abundance in geothermal springs. It can utilize most carbohydrates other than crystalline/non-soluble polymers (e.g. cellulose), but shows no substrate preference. It is a copious producer of extracellular polymeric substance. Genomic analysis of strain T49T identified a wide range of glycosyl hydrolases and carbohydrate ATP-binding cassette transporters, as well as many extracytoplasmic function sigma factors. Based on genomic and physiological characterization, the ecological role of C. calidirosea T49T was proposed to be that of a scavenger, utilizing heterogeneous carbohydrates from degraded biomass within the environment. The C. calidirosea genome was remarkably high in sigma factors but extremely disorganized; many genes typically arranged in operons (e.g. tryptophan synthesis) were instead scattered throughout the genome. To determine whether this apparent genomic disorganisation indicates rapid genomic evolution, we are comparing the sequence of strain T49T to additional isolates of C. calidirosea. I am also interested in understanding how C. calidirosea regulates its genome.
Collaborators: Dr Matthew Stott, GNS Science; Dr Ian McDonald, Waikato University
I am currently seeking highly-motivated, excellent PhD candidates with excellent academic records.
Thesis title “The first insights into the phylogeny, genomics, and ecology of the novel bacterial phylum Armatimonadetes.” Co-supervised with Dr Ian McDonald of Waikato University & Dr Matt Stott of GNS Science. Currently a postdoctoral fellow at Auckland University of Technology.
University of Otago Dean's Bequest Fund
Recent publications (past 5 years)
Lee KC, Stott MB, Dunfield PF, Huttenhower C, McDonald IR, Morgan XC. The Chthonomonas calidirosea genome is highly conserved across geographic locations and distinct chemical and microbial environments in New Zealand's Taupo Volcanic Zone. Appl Environ Microbiol. 2016 May 31;82(12):3572-81. doi: 10.1128/AEM.00139-16. Print 2016 Jun 15.
Hsu T, Joice R, Vallarino J, Abu-Ali G, Hartmann EM, Shafquat A, DuLong C, Baranowski C, Gevers D, Green JL, Morgan XC, Spengler JD, Huttenhower C. Urban Transit System Microbial Communities Differ by Surface Type and Interaction with Humans and the Environment. mSystems Jun 2016, 1 (3) e00018-16.
Yassour M, Lim MY, Yun HS, Tickle TL, Sung J, Song YM, Lee K, Franzosa EA, Morgan XC, Gevers D, Lander ES, Xavier RJ, Birren BW, Ko G, Huttenhower C. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med. 2016 Feb 17;8(1):17. doi: 10.1186/s13073-016-0271-6.
Lee KC, Morgan XC, Power JF, Dunfield PF, Huttenhower C, Stott MB. Complete genome sequence of the thermophilic Acidobacteria, Pyrinomonas methylaliphatogenes type strain K22(T). Stand Genomic Sci. 2015 Nov 14;10:101. doi: 10.1186/s40793-015-0099-5. eCollection 2015. PubMed PMID: 26568784.
Houghton KM, Morgan XC, Lagutin K, MacKenzie AD, Vyssotski M, Mitchell KA, McDonald IR, Morgan HW, Power JF, Moreau JW, Hanssen E, Stott MB. Thermorudis pharmacophila WKT50.2T sp. nov., a novel isolate of class Thermomicrobia isolated from geothermal soil, and emended descriptions of Thermomicrobium roseum, Thermomicrobium carboxidum, Thermorudis peleae and Sphaerobacter thermophilus. Int J Syst Evol Microbiol. 2015 Sep 14. doi: 10.1099/ijsem.0.000598. [Epub ahead of print] PubMed PMID: 26374291.
Börnigen D, Moon YS, Rahnavard G, Waldron L, McIver L, Shafquat A, Franzosa EA, Miropolsky L, Sweeney C, Morgan XC, Garrett WS, Huttenhower C. A reproducible approach to high-throughput biological data acquisition and integration. PeerJ. 2015 Mar 31;3:e791. doi: 10.7717/peerj.791. eCollection 2015. PubMed PMID: 26157642; PubMed Central PMCID: PMC4493686.
Franzosa EA, Hsu T, Sirota-Madi A, Shafquat A, Abu-Ali G, Morgan XC, Huttenhower C. Sequencing and beyond: integrating molecular 'omics' for microbial community profiling. Nat Rev Microbiol. 2015 Jun;13(6):360-72. doi: 10.1038/nrmicro3451. Epub 2015 Apr 27. Review. PubMed PMID: 25915636.
Morgan XC, Kabakchiev B, Waldron L, Tyler AD, Tickle TL, Milgrom R, Stempak JM, Gevers D, Xavier RJ, Silverberg MS, Huttenhower C. Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease. Genome Biol. 2015 Apr 8;16:67. doi: 10.1186/s13059-015-0637-x. PubMed PMID: 25887922; PubMed Central PMCID: PMC4414286.
Yasuda K, Oh K, Ren B, Tickle TL, Franzosa EA, Wachtman LM, Miller AD, Westmoreland SV, Mansfield KG, Vallender EJ, Miller GM, Rowlett JK, Gevers D, Huttenhower C, Morgan XC. Biogeography of the intestinal mucosal and lumenal microbiome in the rhesus macaque. Cell Host Microbe. 2015 Mar 11;17(3):385-91. doi: 10.1016/j.chom.2015.01.015. Epub 2015 Feb 26. PubMed PMID: 25732063; PubMed Central PMCID: PMC4369771.
Joice R, Yasuda K, Shafquat A, Morgan XC, Huttenhower C. Determining microbial products and identifying molecular targets in the human microbiome. Cell Metab. 2014 Nov 4;20(5):731-41. doi: 10.1016/j.cmet.2014.10.003. Epub 2014 Nov 4. Review. PubMed PMID: 25440055; PubMed Central PMCID: PMC4254638.
Franzosa EA, Morgan XC, Segata N, Waldron L, Reyes J, Earl AM, Giannoukos G, Boylan MR, Ciulla D, Gevers D, Izard J, Garrett WS, Chan AT, Huttenhower C. Relating the metatranscriptome and metagenome of the human gut. Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):E2329-38. doi: 10.1073/pnas.1319284111. Epub 2014 May 19. PubMed PMID: 24843156; PubMed Central PMCID: PMC4050606.
Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, González A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe. 2014 Mar 12;15(3):382-92. doi: 10.1016/j.chom.2014.02.005. PubMed PMID: 24629344; PubMed Central PMCID: PMC4059512.
Rooks MG, Veiga P, Wardwell-Scott LH, Tickle T, Segata N, Michaud M, Gallini CA, Beal C, van Hylckama-Vlieg JE, Ballal SA, Morgan XC, Glickman JN, Gevers D, Huttenhower C, Garrett WS. Gut microbiome composition and function in experimental colitis during active disease and treatment-induced remission. ISME J. 2014 Jul;8(7):1403-17. doi: 10.1038/ismej.2014.3. Epub 2014 Feb 6. PubMed PMID: 24500617; PubMed Central PMCID: PMC4069400.
Morgan XC, Huttenhower C. Meta'omic analytic techniques for studying the intestinal microbiome. Gastroenterology. 2014 May;146(6):1437-1448.e1. doi: 10.1053/j.gastro.2014.01.049. Epub 2014 Jan 28. Review. PubMed PMID: 24486053.
Lee KC, Morgan XC, Dunfield PF, Tamas I, McDonald IR, Stott MB. Genomic analysis of Chthonomonas calidirosea, the first sequenced isolate of the phylum Armatimonadetes. ISME J. 2014 Jul;8(7):1522-33. doi: 10.1038/ismej.2013.251. Epub 2014 Jan 30. PubMed PMID: 24477196; PubMed Central PMCID: PMC4069393.
Crowe MA, Power JF, Morgan XC, Dunfield PF, Lagutin K, Rijpstra IC, Vyssotski GN, Sinninghe Damste JS, Houghton KM, Ryan JL, Stott MB. Pyrinomonas methylaliphatogenes gen. nov., sp. nov., a novel group 4 thermophilic member of the phylum Acidobacteria from geothermal soils. Int J Syst Evol Microbiol. 2014 Jan;64(Pt 1):220-7. doi: 10.1099/ijs.0.055079-0. Epub 2013 Sep 18. Erratum in: Int J Syst Evol Microbiol. 2014 Mar;64(Pt 3):1074. Rijpstra, W I C [removed]; Vyssotski, G N S [added]. PubMed PMID: 24048862.
Segata N, Börnigen D, Morgan XC, Huttenhower C. PhyloPhlAn is a new method for improved phylogenetic and taxonomic placement of microbes. Nat Commun. 2013;4:2304. doi: 10.1038/ncomms3304. PubMed PMID: 23942190; PubMed Central PMCID: PMC3760377.
Börnigen D, Morgan XC, Franzosa EA, Ren B, Xavier RJ, Garrett WS, Huttenhower C. Functional profiling of the gut microbiome in disease-associated inflammation. Genome Med. 2013 Jul 31;5(7):65. doi: 10.1186/gm469. eCollection 2013. Review. PubMed PMID: 23906180; PubMed Central PMCID: PMC3978847.
Segata N, Boernigen D, Tickle TL, Morgan XC, Garrett WS, Huttenhower C. Computational meta'omics for microbial community studies. Mol Syst Biol. 2013 May 14;9:666. doi: 10.1038/msb.2013.22. Review. PubMed PMID: 23670539; PubMed Central PMCID: PMC4039370.
Lee KC, Herbold CW, Dunfield PF, Morgan XC, McDonald IR, Stott MB. Phylogenetic delineation of the novel phylum Armatimonadetes (former candidate division OP10) and definition of two novel candidate divisions. Appl Environ Microbiol. 2013 Apr;79(7):2484-7. doi: 10.1128/AEM.03333-12. Epub 2013 Feb 1. PubMed PMID: 23377935; PubMed Central PMCID: PMC3623213.
Morgan XC, Huttenhower C. Chapter 12: Human microbiome analysis. PLoS Comput Biol. 2012;8(12):e1002808. doi: 10.1371/journal.pcbi.1002808. Epub 2012 Dec 27. PubMed PMID: 23300406; PubMed Central PMCID: PMC3531975.
Morgan XC, Segata N, Huttenhower C. Biodiversity and functional genomics in the human microbiome. Trends Genet. 2013 Jan;29(1):51-8. doi: 10.1016/j.tig.2012.09.005. Epub 2012 Nov 7. Review. PubMed PMID: 23140990; PubMed Central PMCID: PMC3534939.
Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, Bousvaros A, Korzenik J, Sands BE, Xavier RJ, Huttenhower C. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012 Apr 16;13(9):R79. doi: 10.1186/gb-2012-13-9-r79. PubMed PMID: 23013615; PubMed Central PMCID: PMC3506950.
Dunfield PF, Tamas I, Lee KC, Morgan XC, McDonald IR, Stott MB. Electing a candidate: a speculative history of the bacterial phylum OP10. Environ Microbiol. 2012 Dec;14(12):3069-80. doi: 10.1111/j.1462-2920.2012.02742.x. Epub 2012 Apr 13. PubMed PMID: 22497633.
Vyssotski M, Ryan J, Lagutin K, Wong H, Morgan X, Stott M. A novel fatty acid, 12,17-dimethyloctadecanoic acid, from the extremophile Thermogemmatispora sp. (Strain T81). Lipids. 2012 Jun;47(6):601-11. doi: 10.1007/s11745-012-3668-z. Epub 2012 Apr 5. PubMed PMID: 22476737.
Vyssotski M, Lee KC, Lagutin K, Ryan J, Morgan XC, Stott MB. Fatty Acids of Chthonomonas calidirosea, of a novel class Chthonomonadetes from a recently described phylum Armatimonadetes. Lipids. 2011 Dec;46(12):1155-61. doi: 10.1007/s11745-011-3597-2. Epub 2011 Jul 31. PubMed PMID: 21805326.
Lee KC, Dunfield PF, Morgan XC, Crowe MA, Houghton KM, Vyssotski M, Ryan JL, Lagutin K, McDonald IR, Stott MB. Chthonomonas calidirosea gen. nov., sp. nov., an aerobic, pigmented, thermophilic micro-organism of a novel bacterial class, Chthonomonadetes classis nov., of the newly described phylum Armatimonadetes originally designated candidate division OP10. Int J Syst Evol Microbiol. 2011 Oct;61(Pt 10):2482-90. doi: 10.1099/ijs.0.027235-0. Epub 2010 Nov 19. PubMed PMID: 21097641.