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Microbial MetabolismSystems Microbiology

Ching-Tsan Huang (黃慶璨)Office: Agronomy Hall, Room 111Tel: (02) 33664454E-mail: cthuang@ntu.edu.tw MIT OCW

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Systems Microbiology aims to integrate basic biological information with genomics, transcriptomics, metabolomics, glycomics, proteomics and other data to create an integrated model of how a microbial cell or community functions. (Nature Review Microbiology)Systems Microbiology seeks to identify how microbial functions evolve and how emergent properties in cells and communities arise from seemingly simple, linear genetic sequences.

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Source: U.S. Department of Energy Genome Programs http://genomics.energy.gov.

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Source: U.S. Department of Energy Genome Programs http://genomics.energy.gov.

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Why Systems Microbiology?

Microbial systems are important and ideal models

Microbes offer important lessons about all life forms

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Disciplines Involving Systems MicrobiologyMicrobiologists,Biochemists,Evolutionary biologistsMathematicians,Computer scientists,Physicists,Chemists,Control theorists,Systems engineers,Geochemists,Atmospheric chemists,Chemical and physical oceanographers,Earth scientists, andBiostatisticians.

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Potential Applications of Systems Microbiology

AgriculturesMedicinesNovel energy production systemsMetabolic engineeringBiocontrolPollution and bioremediationBioterrorism and decontaminationMicrobiological detection systemsGlobal monitoring

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Integrated Systems Microbiology

Microbiology

Computer Science

ChemistryEcology

Mathematics

Molecular Evolution

Microbial - Host System

Multi-Disciplinary

Biocontrol/ Bioremediation

Drug Discovery Antibiotic Resistance DiagnosticsVaccines

• Environmental• Industrial Bioreactors

BioenergyBiosensors

Genetics

•Biomedical

10Utilization of Microbial Inoculants to Promote Sustainable Agriculture

Phytostimulation

Production of IAAACC deaminaseIncrease rooting Increase Nitrogen

uptakeReduced fertilizer

usageReduced nitrate

pollution

Biofertilization

Nitrogen fixationPhosphate solubilizationReduced fertilizer usageReduced water pollution

Antimicrobial MetabolitesReduced pathogensReduced diseaseReduced fungicide usage

Biocontrol

Nutrients

SignalsPrimary metabolismSecondary metabolism

Gene expression

Primary metabolism

Secondary metabolism

Microbial Cell Factory

Bioremediation

Clean-up ofcontaminated

soils

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An Integrated Systems Biology Approach to Elucidating the Nature of Molecular Signalling in Microbial-Host Interactions

Environmental signalsMicrobial signalsQuorum sensing

Signalling and regulatory circuits

Eukaryotic Host cells in culture

Pseudomonas aeruginosa

Secondary metabolitesSignal molecules Biofilm formation

Planktonic cells

CytokinesHost signals

Overall Aim:

To establish the importance of microbial and host signalling in determining the outcome of microbial-host interactions.

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From Metagenomes to Ecosystem Functioning

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Strain-resolved proteomics from environmental samples

14From Proteins to Environments

15From Proteins to Environments

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Experimental Approaches in Systems Biology

Sequencing technologiesA capillary-based Sanger method on sequencing platforms.Massively higher throughput, such as 454 pyrosequencing, SOLiD and Solexa

DNA microarrays and high-throughput sequencingSlides containing spatially organized DNA probes with known sequences for the identification and quantification of fluorescently labelled nucleic acids samples.

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Next Generation Sequencing

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Experimental Approaches in Systems Biology

Proteomics technologiesMass spectrometry (MS)-based approaches for identificationArray-based platforms

Metabolomics technologiesPowerful and accurately predictive approaches Bench-scale assays to high-throughput methods

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Evolution of mass spectrometry-based proteomics from microbial isolates to communities

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LC/MS-based Proteomics

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Mass Spectrometry

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Matrix-assisted laser desorption/ionization-based resequencing

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Technical Challenges In Systems Microbiology

Technical bottlenecksSingle cell measurementsIdentifying and accurately measuring metabolitesCultivationData accessibilityComputational limitationsAnnotation and functional characterization of genesProteomicsHigh-throughput technologies

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Tracking and segmenting single cells