la gramática de la diversidad microbiana víctor de lorenzo centro nal. biotecnologia csic, madrid...

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La gramática de la diversidad microbiana Víctor de Lorenzo Centro Nal. Biotecnologia CSIC, Madrid (Spain)

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La gramática de ladiversidad microbiana

Víctor de LorenzoCentro Nal. Biotecnologia

CSIC, Madrid (Spain)

microorganisms

(156 k)

ecosystems

Known diversity

plant(270 k)

animal(1.230 k)

Existing diversity

animals

plants

microorganisms

microorganisms

200 k

ecosystems

plants(250k)

animal1500k

animalsplants

microbes

human

known existing

fungi80 k

protista100 k

known

eubacteria & archaea

existing

nonculturable

culturable

10 k

True vs. False Diversity..• TV sets• Human languages

1st Question of the day:

How to access Microbial diversity?

The problem of the global genome

genomes sequenced

nu

mber

of

new

gen

es

100%

0%

How many genomes do we need to access microbial diversity

• Bioinformatics• Genomics/sequencing• Gene mining• Predictions from • number of niches • number of genes

New protein folds/megabase ofnew DNA sequence_________________________

Human DNA 1.3Average prokaryotes 172Xylella fastidiosa 377Borrelia burgdorferi 392

num

ber

of

item

sEnzymatic vs. Genetic diversity

Time/year00 30 70 90 00

Novel chemical reactions

Novel genes/Gene variants

Metagenomics

Accessing and exploiting the meta-genome

Cl Cl

Cl Cl

Cl Cl

Cl

Cl

OH

Substrate

Product(s)

XylR*XylR*

Inactive

Active

Pu-lacZPu-Km

Selectable phenotype

Colouredphenotype

Expression Library

a b c d

+

What is a gene?

• One gene-one enzyme?• One gene-one protein?• One gene-one function?• One gene-one protein fold?

.

. .

.

.

.

. .

.

.

. ..

..

The gene landscape

The grammar of Biodiversity...

• The minimal biological diversity unit?• Phonemes (F. de Saussure)• Generative Grammar (N. Chomsky)• Words, sentences, languages• Alphabets, books, editions, libraries• How many books?

Grammar Biological entity

Phoneme Gene/fold/functionWord Operon/complexSentence NetworkBook OrganismLibrary Ecosystem

2nd Question of the day:

How to predict biodegradation?

~ 320 strains~ 650 compounds~ 470 catabolic enzymes~ 730 reactions of environmental interest

In silicobiodegradationof toluene:

Towards predictivebiodegradation

3rd Question of the day:

Can bioinformatics reveal features of regulatory

networks which are opaque to experimentation?

Levels of regulation in the Pu promoter

RNA pol54

IHF

PtsN-PC source FtsH/DnaK

ppGpp

Anti-sigma?

Physiological control

Specificregulation

XylRXylR

CH3

R

Environmental signal

Environmental signal

Environmental signal

Environmental signal

Environmental signal