Upload
ed-dodds
View
78
Download
0
Embed Size (px)
Citation preview
1
SJCRH
Supporting HighSupporting High--throughput throughput BiotechnologiesBiotechnologies in Today’s in Today’s
Research EnvironmentResearch Environment
Clayton W. Naeve, Clayton W. Naeve, PhPh.D..D.
SJCRH
OverviewOverview• Trends in Biomedical Science.• Options.• Organization.
– St. Jude Children’s Research Hospital– Hartwell Center and Molecular Biotechnology
• Integrated Services– High-throughput DNA Sequencing & Genotyping
– Macromolecular Synthesis– Functional Genomics (cDNA microarray laboratory)
– Clinical Applications Core Technology (Affymetrix laboratory)– Proteomics/Mass Spectrometry
– Bioinformatics• Impact• Oversight• Space• Budget• Staff• Summary - Keys to Success
2
SJCRH
Trends in Biomedical ScienceTrends in Biomedical Science
• Multidisciplinary– genetics, molecular biology, computer sciences, mathematics, biostatistics, bioinformatics……
– departmental distinctions are blurring.
– multidisciplinary programs emerging to address specific problems.
• High-throughput– High-throughput biotechnologies becoming critical to competitiveness.
• DNA microarrays.
• Proteomics/Mass spectrometry.• HTS.
• High-throughput DNA sequencing.
• High-throughput SNP detection.
• High-throughput structure analysis.
• Bioinformatics dependent– High-throughput methods.
– HGP etc.
How does an institution provide these “resources” to remain
competitive?
SJCRH
OptionsOptions
• Outsourcing.
• Individual faculty supported biotechnologies.
• Distributed shared resources.
• Consolidated or integrated shared resource(s).
Less Desirable
More Desirable
Hartwell Center for Bioinformatics & Biotechnology@
St. Jude Children’s Research Hospital
3
SJCRH
Hartwell Center Hartwell Center -- OrganizationOrganization
St. Jude Children’s Research HospitalSt. Jude Children’s Research Hospital
– 180 Faculty (~100 basic and ~80 clinical).– 200 postdoctoral fellows.
– 16 laboratory-based research departments.– $250M annual budget, ~$50M derived from research grants.
– Major expansion plan announced in 1999.
SJCRH
Hartwell Center Hartwell Center -- OrganizationOrganization
Hartwell Center (Service) Molecular Biotechnology (Research)
CACT
HT Sequencing.
MacromolecularSynthesis
FunctionalGenomics
Proteomics/MS
Bioinformatics 6 faculty6 postdoctoral fellows
Director, SJCRH
Deputy Director, SJCRH
Director, Hartwell Center
4
SJCRH
• Services:– DNA sequence analysis using high-throughput
methods (robotics, automated sequencers, bioinformatics).
– Genotyping/SNP analysis (FY01).• Resources:
– Instrumentation:• Biomek 2000 robot.• four MJR thermalcyclers .• two ABI 3700 DNA sequencers.• one ABI 3100 Genetic Analyzer.
– Bioinformatics resources:• On-line ordering/tracking.• hcWebFetch (sequence retrieval).• Sequence archives, etc.• Data analysis.
• Staff: 3 staff members.
• Production:– ~1,000,000 bases per month.– >50,000 templates/year.
Hartwell Center Hartwell Center -- ServicesServicesHighHigh--throughput DNA Sequencing & Genotypingthroughput DNA Sequencing & Genotyping
SJCRH
Hartwell Center Hartwell Center -- ServicesServicesMacromolecular SynthesisMacromolecular Synthesis
• Services– Organic synthesis of DNA and protein molecules (using
automated instruments).
• Resources– Instrumentation:
• one PE/ABI 394 DNA synthesizers.• two PE/ABI 3900 (48 col.) DNA synthesizer.• two PE/ABI 431 peptide synthesizers• one Advanced ChemTech 396 MPS.• one Rainin Symphony Multiplex (12 col.)• analytical and preparative HPLCs.
• Staff: 3 staff members.
• Production:– 10,000 oligonucleotides/year (66,000 oligo’s to date).– 1,500 peptides/year (5,346 to date).
5
SJCRH
Hartwell Center Hartwell Center -- Services Services Functional GenomicsFunctional Genomics
• Services– The measurement of gene expression using DNA
microarray technology.• cDNA library management
– 75,000 cDNA clones (mouse and human)• Dye-labeling (direct or indirect)• cDNA microarray production• hybridization• scanning, gridding, data upload to ArrayDB
• Resources– Instrumentation:
• Flexys (library management)• HiGro (clone growth)• RevPrep (plasmid preps)• MWG RoboAmp (PCR reaction setup)• Qiagen Biorobot 3000 (PCR reaction cleanup)• OmniGrid (arrayer)• GeneTAC• ScanArray 5000 & ScanArray Lite
SJCRH
Hartwell Center Hartwell Center -- ServicesServicesFunctional GenomicsFunctional Genomics
– Bioinformatics:• ScanArray• ScanAlyze (image analysis)• ArrayDB (array database, Oracle version)• GenExplore (cluster analysis software)• GenoMax• Spotfire
• Staff: 3 staff members.
• Production:– 75 hybridizations in first month.
6
SJCRH
Hartwell Center Hartwell Center -- ServicesServicesClinical Applications Core TechnologyClinical Applications Core Technology
• Services– Measure gene expression levels using oligonucleotide
microarrays and develop clinical applications for the technology (GeneChips, Affymetrix, Inc.).
• RNA QC using Agilent “Lab-on-a-Chip”.• Biotin-labeling target RNA.• Hybridization to GeneChips.• Image analysis.• Bioinformatics support.
• Resources– Affymetrix GeneChips (human, mouse, cancer gene,
yeast, etc.)– Instrumentation
• Hybridization oven (2).• Fluidics workstations (3).• scanning laser confocal reader (2).• computer workstation (4).
– Bioinformatics Resources• Affymetrix LIMS. , GenExplore, Spotfire, GenoMax.
• Staff: 2 staff members.• Production:
– 900 GeneChips in first 9 months.– 40-50 arrays/week. SJCRH
Hartwell Center Hartwell Center -- ServicesServicesProteomicsProteomics/Mass Spectrometry/Mass Spectrometry
• Services– High-throughput protein identification.
• 2-D gel analysis• Mass spectrometry
• Resources– Instrumentation:
• ABI 494 cLC Procise Protein Sequencer.• ABI 177AMicroblotter.• Biacore 3000.• PerSeptive Biosystems, Inc. Voyager DE RP MALDI -TOF mass spectrometer.• Finnigan LCQdecca ion-trap mass spectrometer.• Micromass LCT.• Michrom Magic capillary LC system.• Waters Masslynx capillary LC system.• Fuji LAS1000 image analysis system.
– Bioinformatics resources:• Xcaliber, SEQUEST, Protein Prospector, etc.
• Staff: 5 staff members.• Production:
– Microsequence analysis (200 samples/year, 1,300 to date).– Molecular Interaction analysis (Biacore, 1600 samples to date)– Mass Spectrometry (2,700 samples/year, 8,556 total).
7
SJCRH
Hartwell Center Hartwell Center -- Services Services BioinformaticsBioinformatics
• Services– Bioinformatics Support [~1000 user accounts].
– High-Performance Computing Environment.– Hartwell Center laboratory support.
• Resources– Computer Hardware:
• Compaq GS140 (10 cpus, 12 Gb RAM); Oracle DB server.• SGI InfiniteReality OnyxII (16 cpus, 9 Gb RAM);
Applications/Graphics server.• SANs system (6 Tb disk storage, 7 Tb tape backup system)• many other small systems supporting various applications.
– Software/Databases:• DNA/Protein Sequence Analysis Software (Vector NTI,
GenoMax, GCG, Spotfire, etc.)• DNA/Protein Sequence Databases (all public, Celera , etc.• ArrayDB and Affymetrix LIMS system for array data• Hartwell Center Database (invoicing, on -line
ordering/tracking, etc.)– -Internet Resources:
• Firewall• Internet Connectivity (T3 lines)
• Staff: 10 staff members.High-Performance Computing Facility
SJCRH
• Scientific Impact– DNA Sequence Analysis: 191,074 templates; 69,500,000 base pairs.
– DNA Synthesis: 65,911 oligonucleotides; 1,690,000 base pairs.– Peptide Synthesis: 5,346 peptides; 67,246 couplings.
– Protein Sequence Analysis: 1,321 samples; 13,030 residues.
– Mass Spectrometry: 8,556 samples.
– Affymetrix GeneChip Analysis: >900 samples in first 9 months.– cDNA Microarray Hybridizations: 75 samples in first month.
– Bioinformatics support for ~1000 users
– Contributions to hundreds of publications, grant applications, etc.
– Key role in numerous discoveries.
• Organizational Impact– Promotes collaborative studies.
– Promotes the application of state -of-the-art technology in research efforts
– Financial savings realized by consolidation• common database for invoicing.
• single on-line ordering/tracking system.
• single administrative staff.
• Recruiting Impact– Key role in recruiting new faculty, department chairs, postdoctoral fellows, staff.
– Impacts fund-raising.
Hartwell Center Hartwell Center -- ImpactImpact
8
SJCRH
Hartwell Center Hartwell Center -- OversightOversight
• Hartwell Center Scientific Advisory Board– External scientific advisory group; meets yearly.
– Boguski , Meltzer, Burlingame, States, Curran, Downing• Hartwell Center Advisory Board
– Internal advisory group; meets quarterly.– benefactor, 4 members of ALSAC Board of Governors, Deputy Director, 2 Dept.
Chairs.
• Hartwell Center Liaison Group– Internal departmental representatives; meets bi-monthly.
– 21 representatives from all laboratory-based departments at SJCRH.
SJCRH
Hartwell Center Hartwell Center -- SpaceSpaceHigh-throughput DNA Sequencing & Genotyping 440 sq. ft.Macromolecular Synthesis 440 sq. ft.Functional Genomics 660 sq. ft.Proteomics 660 sq. ft.Mass Spectrometry 500 sq. ft.Clinical Applications Core Technology 800 sq. ft.Bioinformatics 3000 sq. ftAdministrative/office space 1000 sq. ft
Total 7,500 sq. ft.
9
SJCRH
Hartwell Center Hartwell Center -- BudgetBudget
Budget FY 2000 FY 2001 FY 2002
Opera t i ng $ 3 , 4 2 7 , 0 2 6 $ 4 , 5 8 8 , 9 2 0 $ 5 , 2 3 6 , 6 6 4
C a p i t a l & R e n o v a t i o n s 4 ,433 ,689 2 ,622 ,000 2 ,312 ,000
Ind i rec t Cos ts 1 ,960 ,729 2 ,339 ,214 2 ,578 ,699
S u b t o t a l 9 ,821 ,444 9 ,550 ,134 1 0 , 1 2 7 , 3 6 3
Less : Mo lecu la r Pa tho logy (1 ,495,300) (1 ,063,496) (1 ,132,436)
Tota l Hartwel l Center $ 8 , 3 2 6 , 1 4 4 $ 8 , 4 8 6 , 6 3 8 $ 8 , 9 9 4 , 9 2 7
SJCRH
Hartwell Center Hartwell Center -- StaffStaff
• C l a y t o n W . N a e v e , P h. D .
• C l i v e S laugh te r , P h. D .
• B r e n d a A l n e m y
• K r i s h n a S a n k h a v a r a m
• A n d r e w P a p p a s
• S c o t t M a l o n e
• P e r d e e p M e h t a , P h. D .
• Bill P a p p a s
• M a t t S t i n e
• Karen R a k e s t r a w
• M a r g a r e t C i r t a i n
• S t e v e n T u r n e r
• S c o t t O l s o n
• A n u S a n k h a v a r a m
• P h i l i p P o s t o n, P h. D .
• C h r i s t p h e r P e t u c c i , P h. D .
• C h r i s t i n e S h a m b l i n
• B o b C a s s e l l
• S t e p h a n i e T a t e
• D e a n n a N a e v e
• L i l i M a l e k i
• B i l l Lewi s , P h. D .
• D i v y e n Patel , P h. D .
• D a w n W i l k i n s , P h.D . ,V i s i t i ng Sc i en t i s t
• Er i c D u n c a v a g e, In te rn
• J e n n i f e r C a m p b e l l
• J o h n M o r r i s
• A s h u t o s h M i s h r a
• V i c k i B e a l
• Pa t r i c i a Fo rd
3 0 s t a f f t o t a l , 7 Ph .D.s
10
SJCRH
Summary Summary -- Key Elements to SuccessKey Elements to Success
• S t r a t e g i c P l a n n i n g– Applied sciences/services must be integral to institution’s research plan.
– Scientific direction must guide the deployment of biotechnologies.
• L e a d e r s h i p– Multidisciplinary expertise.
– Vision.
• A t t r a c t i v e C a r e e r P a t h– “Service” is not a pejorative word.
– Appropriate career ladder to attract and retain skilled staff.
• I n t e g r a t i o n o f K e y T e c h n o l o g i e s– Depends on research environment.
– High -throughput biotechnologies likely required.
– Bioinformatics essential.
• S c i e n t i f i c O v e r s i g h t– Critical to help guide development, establish strategic plan, ov ersee progress.
• B u d g e t S u p p o r t– Appropriate and consistent to meet institutional needs.
SJCRH
Hartwell Center Web SiteHartwell Center Web Site
http://www.hartwellcenter.org
11
SJCRH
Thank You!