New Trends in Microbiology

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    New Trends in Microbiology

    Zhihong Hu

    Wuhan Institute of Virology

    Chinese Academy of Sciences

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    Outline

    I. Microbes and Microbiology

    II. Environmental Microbiology

    III. Microbial Genomics

    IV. Emerging Infectious Disease

    V. Integrative Microbiology

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    I. Microbes and Microbiology

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    Microbes are the Basis of Life

    Microbes were the first life

    form on earth

    The root of the tree of life

    Microbes have the greatest

    genetic and metabolic

    diversity

    Define the boards of the

    biosphere

    3.5 billion years old prokaryotic fossil

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    0

    1000

    2000

    3000

    4000

    5000

    2000 2005 2010 2015 2020

    Total Ethanol

    From cellulose

    From corn

    Bio-Ethanol

    Biofuels Will Depend on Microbes

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    Microbes are Vital to Human Health

    More than 90% of the cells in our bodies are

    microorganisms

    Necessary for digestion and absorption of nutrients

    Critical for the development of vascular and

    immune systems

    Pathogens of infectious diseases

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    Microbiology is Fundamental to Biology

    Microbes are ideal model for studying life

    science

    Microbiology plays important roles in

    biochemistry, genetics, evolution, molecular

    biology, etc.

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    The Tree of Life Before Molecular Microbiology

    Five Kingdoms of Life

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    II. Environmental Microbiology

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    Amann, Ludwig and Schleifer, Microbiol. Rev.59, 1995

    ~99% of the Microbes on Earth are Uncultured

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    Metagenomics:

    In situ Microbial Community Analysis

    To Understandthe Whole,

    One Must Study

    the Whole

    Newman & Banfield, Science 296, 2002

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    Hot Spring in Tengchong,

    Yunnan, China (75 oC)Bao et al., Genome Research 12, 2002

    Thermoanaerobacter

    tengcongensis

    Genome ofThermoanaerobacter tengcongensis

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    Proteomics ofT. tengcongensis

    Wang et al., Proteomics, 2004

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    The Significance ofExtremophiles Researches

    Origin of life and evolution

    Adaptation of life to extreme

    environments Life on other planets

    Potential applications in

    industry, agriculture,

    medicine, and environmental

    remediation

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    Some Ongoing Research Activities

    in Environmental Microbiology in China

    Metagenomic projects: Continental

    subsurface deep drilling, deep sea, hot

    springs, human intestinal tract, etc. Genetic bases and survival strategies

    of extremophiles

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    III. Microbial Genomics

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    Can we Define a Minimal set of Genes Essential for Life?

    DNA metabolism: 16

    RNA metabolism: 106 Protein processing, folding,

    secretion: 15

    Cellular processing: 5

    Energetic and intermediary

    metabolism :56

    Poorly characterized: 8

    Total: 206 genes

    Protein-coding genes

    in the hypothetical minimal cell:

    Gil et al., Microbiol Mol Biol Rev. 68, 2004

    Mycoplasma genitalium:

    382 protein-coding genes

    are essential.

    Glass et al., PNAS 103, 2006.

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    Transmission and Expansion ofY. pestis in China

    Zhou et al., J. Bacteriol 186, 2004

    DFR17

    G05,06,08

    G10

    G14

    G04

    G01,02,03

    G08

    G07

    G09

    G09

    G09

    G10

    G11,12

    G11,13

    G05,11

    G14

    G?

    DFR14,22

    DFR

    04

    DFR03,0

    4DFR05

    DFR13

    DFR06,11,12,13,18,19,20

    DFR06,11,12,13,18,19,20

    DFR06,07,15,16

    DFR10DFR04,21

    DF

    R

    0

    2

    DFR17

    DFR

    02

    DFR0

    9

    Antiqua Antiqua

    Orientalis

    Medievalis

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    Cluster I - Synthesis and transportof ribosome proteins

    Cluster II - Uptake and utilizationof iron

    Cluster III - Sulfur metabolism

    Cluster IV - Energy metabolism

    Global Gene Transcription Profile ofY. pestis

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    Metabolic Pathways

    inLeptospira interrogans Lai

    Ren et al., Nature 422, 2003

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    Deng & Bai, Nat. Prod. Rep., 2006

    Metabolic Engineering: Antibiotic Biosynthesis

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    IV. Emerging Infectious Diseases

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    Mechanisms of Viral Emergence

    Transmission tohumans

    Inter-human

    transmission

    and further spread

    Virus Intermediate hostAnimal reservoirVector

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    The full-length genome sequences

    had 99.8% identity to the human SARS-CoV.

    Guan et al., Science 302, 2003

    Masked Palm Civets Harbouring SARS-CoV

    Masked Palm Civets

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    He et al., Science 303, 2004

    Phylogenetic Analysis Linked Early Cases to Civets

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    Song et al., PNAS 102, 2005

    Re-emerging of SARS in 2003/2004 were found

    Directly Linked to Civets

    3 animalsamples

    2 humansamples

    Very mild symptoms

    No human-to-human transmission

    Direct/indirect civet contact history

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    Qu et al., J Biol Chem, 2005

    Viral Adaptation to Human Receptors is

    Critical for Human to Human Transmission

    Li et al., Science, 2005

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    Civets were viral positive in markets but negative in farms

    Kan et al., J. Virol., 2005

    Civet: Animal Reservoir or Intermediate Host?

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    Bats?Bats?

    One of the largest and the most diverse groups of

    mammals which originated 50 million years ago

    More than 80 bat viruses belonging to 10 virus families

    were reported

    Bats are natural reservoirs of a numbers of viruses such

    as Hendra, Nipah, Ebola and rabies

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    Li et al., Science 310, 2005

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    RBDS1 domainS2 domain

    TM Cyto

    Bat SARS-like Virus may not Infectious to Human

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    Market civet

    Human

    Bat?Otheranimals

    Transmission Chain of SARS-CoV?

    Wild civet

    Farm civet

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    VI. Integrative Microbiology

    Microbiology

    Bioinformatics

    Chemistry

    Ecology

    Nanotechnology

    Geology

    Engineering

    GeneticsImmunology

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    Bioinformatics

    GENE EXPRESSION

    PROFILES

    PROTEIN

    INTERACTION DATA

    GENE ONTOLOGY

    PROTEIN COMPLEX

    DATA

    PATHWAY DATA

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    True-color image of a Trichodesmium bloom (A), the Trichodesmiumderived chlorophyll (B), and modeled N2 fixation (C).

    Ecology:Remote Sensing for Tracking Marine Microbial Ecosystem

    Capone & Subramaniam, ASM News 71, 2005

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    Nanotechnology and Microbiology

    Using nanotechnology to study microbiology:

    - Imaging single molecules

    - Poking and pulling nanoscale objects (laser traps,

    optical tweezer)

    - Determining spatial organization in living

    microbes (AFM, near/far field microscope)

    Contribution of microbiology to nanotechnology

    Merz et al.,

    Nature 407, 2000

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    New Trends in Microbiology

    Environmental microbiology

    Microbial genomics

    Emerging infectious disease

    Biocomplexity

    The origins and history of life

    Engineering of microbes to improve the quality of life

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    Thank You