Demys&fying Medicine 29 March 2016...Dobell, C. Antony Van Leeuwenhoek and His “Little...

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Demys&fyingMedicine29March2016

TheHumanMicrobiomeProjectca.1690

Antony van Leeuwenhoek Three important points 1.  The first direct observation of

bacteria was of those from within the human mouth.

2.  No association between microbes and disease

3.  This first observation revealed human-associated microbial communities to be complex

"...[T]heres<ckethorgrowethbetweensomeofmyfront[teeth]andmygrinders...aliDlewhitemaDer,whichisasthickasif'twerebaDer.Onexaminingthis...Imostalwayssaw,withgreatwonder,thatinthesaidmaDerthereweremanyveryliDlelivinganimalcules,verypreLlya-moving”

Dobell, C. Antony Van Leeuwenhoek and His “Little Animalcules.” London. Constable & Co. 1932. Print.

TheHumanMicrobiomeProjectca.2016

HumanMicrobiome

HumanGenome

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TheHumanMicrobiomeProject2013

NetworkInferenceCo-occurrenceorco-exclusionobserva<onsminedtoiden<tysta<s<callysignificantrela<onships.TaxaclusterbasedonbodysiteIsthisabiologicallyrelevantspa<alscales?

Faust, et al. 2012. PLoS Comput. Biol. 8:e1002606

Spa<aldistribu<onofmicrobes:relevantscales

MowatandAgace.2014.Nat.Rev.Immunol.14:667-685. Grice and Segre. 2011. Nat. Rev. Microbiol. 9:244-253

Gutmicrobiota Skinmicrobiota

Ahypothesisforthestructureofdentalplaquebiofilms

Kolenbrander,etal.2010NatRevMicrobiolJabra-Rizk,etal.1999JClinMicrobiol

MicrobialFluorescenceinsituHybridiza<on

Nature Reviews | Microbiology

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Washing

Amann, R. & B. Fuchs. 2008 Nat. Rev. Microbiol. 6:339-348

Spa<aldistribu<onofmicrobes:relevantscales

MowatandAgace.2014.Nat.Rev.Immunol.14:667-685. Grice and Segre. 2011. Nat. Rev. Microbiol. 9:244-253

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Rhodamine Red XAlexa fluor 594Alexa fluor 647

Structural Analysis of a Natural Community: Human Dental Plaque

Imageofafieldofviewofsemi-dispersedhuman

dentalplaque

Selenomonas

Veillonella

Fusobacterium PorphyromonasPasteurellaceae CapnocytophagaNeisseriaceae Streptococcus

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Structural Analysis of a Natural Community: Human Dental Plaque

Model images of randomly placed cells

Selenomonas

Veillonella

Fusobacterium PorphyromonasPasteurellaceae CapnocytophagaNeisseriaceae Streptococcus

Prevotella

Gemella

Treponema Actinomyces

CampylobacterRothia

Leptotrichiaunknown

Observed image of plaque

Structural Analysis of a Natural Community: Human Dental Plaque

Streptococcus

Prevotella

Porphyromonas

Actinomyces

Fusobacterium

Rothia

Neisseriaceae

Gemella

Veillonella

Pasteurellaceae

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Biogeographyofthehumanmicrobiomeatthemicronscale

MarkWelch,etal.2015.PNAS

Hedgehogstructureindentalplaque

MarkWelch,etal.2015.PNAS

Corncobstructuresattheborderofhedgehogstructures

MarkWelch,etal.2015.PNAS

Modelhypothesisofhedgehogstructure

tooth$anoxic$

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MarkWelch,etal.2015.PNAS

Hedgehogstructuresasanecosystem

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occupyingnichesTrophicinterac<onsEnvironmentalinfluenceRoleofcell-to-cellcontact

MarkWelch,etal.2015.PNAS

Frameworkfororalmicrobiomefunc<onalstudy

KiDelmann,etal.2013.PLoSOne8:e47879

Ribosome

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microbes

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microbialco-occurrence

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Duran-Pinedo,etal.2015.ISMEJ

Metatranscriptomics

daSilva,DorresteinandQuinn.2015PNAS

MetabolomicsKolenbrander,etal.2010.Nat.Rev.Microbiol

Invitrobiofioms

ExploratorySurveys LaboratoryExperiments

Steenackers,etal.2016.FEMSMicrobiolRev.

Computa<onalmodeling

Acknowledgements•  NICHD

–  JenniferLippincoDSchwartzLab

•  NHGRI–  JulieSegreLab

•  ForsythIns<tute– GaryBorisyLab

•  MarineBiologicalLab–  RudolfOldenbourg–  JessicaMarkWelch

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