11/4/15 Finding a(n) (Infection) Needle in a(n) (-omic) Haystack Juris A. Grasis Computational & Comparative Genomics Course Cold Spring Harbor Laboratory 3 November 2015 There Are A Lot Of Viruses … • Viruses are the most abundant biological entities in the world – 1031 viruses in the biosphere – 1023 viral infections occurring every second – Most diverse biological entities • On average, there are 10 bacterial cells for every host cell … and 10 viruses (bacteriophage) for every bacterial cell … so roughly, 100 viruses for one host cell • The Human Virome • 1013 Human cells • 1014 Bacterial cells • 1015 Viruses • 45% of the Human genome consists of TEs Fundamentals of Molecular Virology, 2007 1 11/4/15 There Are A Lot Of Viruses … • Viruses are the most abundant biological entities in the world – 1031 viruses in the biosphere – 1023 viral infections occurring every second – Most diverse biological entities • On average, there are 10 bacterial cells for every host cell … and 10 viruses (bacteriophage) for every bacterial cell … so roughly, 100 viruses for one host cell • The Human Virome • 1013 Human cells • 1014 Bacterial cells • 1015 Viruses • 45% of the Human genome consists of TEs There Are A Lot Of Viruses … • Viruses are the most abundant biological entities in the world – 1031 viruses in the biosphere – 1023 viral infections occurring every second – Most diverse biological entities • On average, there are 10 bacterial cells for every host cell … and 10 viruses (bacteriophage) for every bacterial cell … so roughly, 100 viruses for one host cell • The Human Virome • 1013 Human cells • 1014 Bacterial cells • 1015 Viruses • 45% of the Human genome consists of TEs Illustration by Charls Tsevls 2 11/4/15 Survival in a World of Viruses With that many viruses in the world, why are we not sick all the time? How do “simple” organisms survive in a world full of viruses? How do “simple” organisms survive for so long? Hydra As A Model For Holobiont Interactions • Hydra are freshwater Cnidarians • Within Cnidaria there are five classes • Hydrozoa • Hydra viridissima • Hydra oligactis • Hydra magnipapillata • Hydra vulgaris • Algal endosymbiont containing and lacking animals • Simple body architecture consisting of two monolayered epithelia • Ectoderm exposed to environment • Endoderm exposed to gastric cavity • Similar in morphology and function as the mammalian intestine • Useful model for studying host regulation of mucosal-microbiota interactions 3 11/4/15 Hydra As A Model For Holobiont Interactions • Hydra are freshwater Cnidarians • Within Cnidaria there are five classes • Hydrozoa • Hydra viridissima • Hydra oligactis • Hydra magnipapillata • Hydra vulgaris • Algal endosymbiont containing and lacking animals • Simple body architecture consisting of two monolayered epithelia • Ectoderm exposed to environment • Endoderm exposed to gastric cavity • Similar in morphology and function as the mammalian intestine • Useful model for studying host regulation of mucosal-microbiota interactions Hydra As A Model For Holobiont Interactions • Hydra are freshwater Cnidarians • Within Cnidaria there are five classes • Hydrozoa • Hydra viridissima • Hydra oligactis • Hydra magnipapillata • Hydra vulgaris • Algal endosymbiont containing and lacking animals • Simple body architecture consisting of two monolayered epithelia • Ectoderm exposed to environment • Endoderm exposed to gastric cavity • Similar in morphology and function as the mammalian intestine • Useful model for studying host regulation of mucosal-microbiota interactions Bosch, Gut Microbes (2012) 4 11/4/15 What are the Viruses Associating with Hydra? Isolation and Sequencing of Viruses 5 11/4/15 Hydra Species are Colonized by Species-Specific DNA Viruses http://on.cc.com/1h87LkK 6 11/4/15 Since Hydra Associate With So Many Viruses, Why Aren’t Hydra Sick All the Time? How Do Hydra Respond to Viral Elements? • How are Hydra recognizing viruses in their environment? • Conserved TLR pathway • Conserved RNAi pathway • Antimicrobial secretion 7 11/4/15 Would You Like to Play a Game? Hydra Are More Responsive to Foreign Viruses 8 11/4/15 Hydra Are More Responsive to Foreign Viruses Finding the Infection 9 11/4/15 RNASeq Unmapped Reads Viral Metagenome Hits To Do • Look at the data! • Other BLAST searches • Specific viral protein BLAST searches • Identify and isolate Hydra-specific virus 10 11/4/15 Thank You! 11 11/4/15 There Are A Lot of Viruses in the World A Numbers Game • 2 x 103 people living in Laurel Hollow • 8 x 106 people living in New York (City) • 2 x 107 people living in New York (Metro) • 3 x 108 people living in the United States • 7 x 109 people living in the world today • 1 x 1011 people have lived on this planet • 3 x 1011 stars in the Milky Way galaxy • 7 x 1017 grains of sand on Earth • 1 x 1023 stars in the known universe These numbers do not approach the number of viruses in the world! 12 11/4/15 A Model For Holobiont Interactions • Holobiont – Metaorganism – Functional association between the Host, prokaryotes, eukaryotes, and viruses • Need to develop a model organism with a limited number of microbial partners – Ability to deconstruct host- microbe interactions • A living test-tube representing an ancient animal phylum – Principles for recognition, maintenance, and colonization A Model For Holobiont Interactions • Holobiont – Metaorganism – Functional association between the Host, prokaryotes, eukaryotes, and viruses • Need to develop a model organism with a limited number of microbial partners – Ability to deconstruct host- microbe interactions • A living test-tube representing an ancient animal phylum – Principles for recognition, maintenance, and colonization 13 11/4/15 A Model For Holobiont Interactions • Holobiont – Metaorganism – Functional association between the Host, prokaryotes, eukaryotes, and viruses • Need to develop a model organism with a limited number of microbial partners – Ability to deconstruct host- microbe interactions • A living test-tube representing an ancient animal phylum – Principles for recognition, maintenance, and colonization 14 .