Microbial Genomics 2008Microbial Genomics 2008

Lake Arrowhead, California Lake Arrowhead, CaliforniaConference Review

Morgan Langille

Where is Lake Arrowhead?

Welcome and IntroductionWelcome and Introduction

OverviewOverview

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)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.)

Genomic Encyclopedia of Bacteria Genomic Encyclopedia of Bacteria and Archaea (GEBA) – J. Eisenand 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/

Human Microbiome Project (HMP) Human Microbiome Project (HMP) – George Weinstock– George Weinstock

Samples from 250 subjects

15 body sites◦ GI (1)◦ Urogenital (3)◦ Oral (4)◦ Nasal (2)◦ Skin (4)◦ Blood (1)

HMPHMP

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 MetagenomicsViral Ecology Using Metagenomics-Eric Wommack-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

VocabularyVocabulary

Provide a list of relevant terms and their definitions

Topic TwoTopic Two

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

More informationMore information

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

SummarySummary

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training on the job Request feedback about this training

session

Antibacterial DiscoveryAntibacterial Discovery- Lynn Silver - 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

Essential Genes in YeastEssential Genes in YeastM. Hillenmeyer (Stanford)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

Persister CellsPersister CellsKim Lewis (NorthEastern Univ.)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

Persister Cells cont.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.”

My ThoughtsMy 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)

Questions?Questions?