Microbial Genomics 2008 Lake Arrowhead, California Conference Review Morgan Langille

Where is Lake Arrowhead?

Welcome and Introduction

Overview Give an overview of the subject Explain why this training is important to the staff members List the topics to be covered Explain how the individual topics fit together

Give an overview of the subject

Explain why this training is important to the staff members

List the topics to be covered

Explain how the individual topics fit together

Biofuels – James Liao (UCLA) Goal is to replace 30% by 2030 How much is 30%? 60 Billion gallons per year 75 Million acres 75% of california Metabolic engineering of E.coli Produce higher alcohols (e.g. isobutanol) from glucose Existing infrastructure (same engines, same delivery, etc.)

Goal is to replace 30% by 2030

How much is 30%?

60 Billion gallons per year

75 Million acres

75% of california

Metabolic engineering of E.coli

Produce higher alcohols (e.g. isobutanol) from glucose

Existing infrastructure (same engines, same delivery, etc.)

Genomic Encyclopedia of Bacteria and Archaea (GEBA) – J. Eisen Sequence bacterial genomes that will sample more branches of the tree of life Reduce sequencing bias that currently exist Annotation by identifying more protein families Anchoring of metegenomic data Gene discovery, HGT, duplication, etc. Pilot project to sequence 100 genomes 60 phylogentically diverse 40 within Actinobacteria 19 (56?) finished Data being released to JGI and Genbank http://www.jgi.doe.gov/programs/GEBA/

Sequence bacterial genomes that will sample more branches of the tree of life

Reduce sequencing bias that currently exist

Annotation by identifying more protein families

Anchoring of metegenomic data

Gene discovery, HGT, duplication, etc.

Pilot project to sequence 100 genomes

60 phylogentically diverse

40 within Actinobacteria

19 (56?) finished

Data being released to JGI and Genbank

http://www.jgi.doe.gov/programs/GEBA/

Human Microbiome Project (HMP) – George Weinstock Samples from 250 subjects 15 body sites GI (1) Urogenital (3) Oral (4) Nasal (2) Skin (4) Blood (1)

Samples from 250 subjects

15 body sites

GI (1)

Urogenital (3)

Oral (4)

Nasal (2)

Skin (4)

Blood (1)

HMP Sequencing 900 bacterial strains 85% draft 15% finished 1 year! Developing sequencing/annotation standards “ finished”, “gene lists” (?), etc. Major focus on development of computational tools HMP Data Analysis and Coordination Center (DACC) Starting in 2009 with a $14 M budget http://hmp.nih.gov/ International Human Microbiome Consortium

Sequencing 900 bacterial strains

85% draft

15% finished

1 year!

Developing sequencing/annotation standards

“ finished”, “gene lists” (?), etc.

Major focus on development of computational tools

HMP Data Analysis and Coordination Center (DACC)

Starting in 2009 with a $14 M budget

http://hmp.nih.gov/

International Human Microbiome Consortium

Viral Ecology Using Metagenomics -Eric Wommack Marine Viromes (PMID: 17090214) 91.4% have no homologs 4.5% have some similarity to bacteria “ Unknown does not mean unimportant!” When T4 lyze there is 4X more virus DNA than bacteria

Marine Viromes (PMID: 17090214)

91.4% have no homologs

4.5% have some similarity to bacteria

“ Unknown does not mean unimportant!”

When T4 lyze there is 4X more virus DNA than bacteria

Vocabulary Provide a list of relevant terms and their definitions

Provide a list of relevant terms and their definitions

Topic Two Explain this topic Give an example Provide an exercise to reinforce learning

Explain this topic

Give an example

Provide an exercise to reinforce learning

More information List other training sessions List books, articles, and online sources List consulting services and other sources

List other training sessions

List books, articles, and online sources

List consulting services and other sources

Summary List the topics that were covered Explain any requirements for applying this training on the job Request feedback about this training session

List the topics that were covered

Explain any requirements for applying this training on the job

Request feedback about this training session

Antibacterial Discovery - Lynn Silver Inhibitors of “novel targets” not really productive in last 20 years Maybe “old” is better Often tend to target multiple targets E.g. Ribosomes, complex structures BIG problem is drug entry into cell So not really a question of targets Should focus on entry and how to avoid efflux Endow chemical libraries with properties that favour entry

Inhibitors of “novel targets” not really productive in last 20 years

Maybe “old” is better

Often tend to target multiple targets

E.g. Ribosomes, complex structures

BIG problem is drug entry into cell

So not really a question of targets

Should focus on entry and how to avoid efflux

Endow chemical libraries with properties that favour entry

Essential Genes in Yeast M. Hillenmeyer (Stanford) 20% essential yeast genes in complex media Have a bar-coded knock out for every gene 1144 chemical environmental genomic assays 97% show a growth phenotype

20% essential yeast genes in complex media

Have a bar-coded knock out for every gene

1144 chemical environmental genomic assays

97% show a growth phenotype

Persister Cells Kim Lewis (NorthEastern Univ.) Persisters are dormant cells that exist within a bacterial population not mutants Max. ~1% stationary phase Tolerant to antibiotics due to targets being shut down Essentially antibiotics just wash over cells without killing Proven using a growth inhibitor to create antibiotic resistant bacteria Found that late isolates of P. aeruginosa from CF patients had high levels of persister cells

Persisters are dormant cells that exist within a bacterial population

not mutants

Max. ~1% stationary phase

Tolerant to antibiotics due to targets being shut down

Essentially antibiotics just wash over cells without killing

Proven using a growth inhibitor to create antibiotic resistant bacteria

Found that late isolates of P. aeruginosa from CF patients had high levels of persister cells

Persister Cells cont. Unculturables Dormant not dead May require molecules from neighbouring bacteria strains Spotted E. coli on plate with unculturables new strain pops up around E. coli Fount mutant (sideophore) that shut down growth Isolated protein caused unculturable strain to grow “ Dormancy is the default mode of bacterial life.”

Unculturables

Dormant not dead

May require molecules from neighbouring bacteria strains

Spotted E. coli on plate with unculturables

new strain pops up around E. coli

Fount mutant (sideophore) that shut down growth

Isolated protein caused unculturable strain to grow

“ Dormancy is the default mode of bacterial life.”

My Thoughts One of the best conferences I have attended Pros Great food, location (all-in-one), speakers Cons Not very international 1/2 (out of 5)

One of the best conferences I have attended

Pros

Great food, location (all-in-one), speakers

Cons

Not very international

1/2 (out of 5)

Questions?