The document describes the Hartwell Center at St. Jude Children's Research Hospital, which provides integrated high-throughput biotechnology services and resources to support research. The Center consolidates services like DNA sequencing, microarray analysis, proteomics, and bioinformatics. It has over 30 staff members and provides resources like automated lab equipment, databases, and high-performance computing. The Center aims to promote collaborative research through these shared resources and has impacted over 500 publications. Key elements of its success include strategic planning, leadership, career opportunities for staff, integration of technologies, scientific oversight, and consistent budget support.

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Supporting HighSupporting High--throughputthroughput
BiotechnologiesBiotechnologies in Today’sin 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

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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?
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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

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Hartwell CenterHartwell 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 CenterHartwell Center -- OrganizationOrganization
Hartwell Center (Service) Molecular Biotechnology (Research)
CACT
HT Sequencing.
Macromolecular
Synthesis
Functional
Genomics
Proteomics/
MS
Bioinformatics
6 faculty
6 postdoctoral fellows
Director, SJCRH
Deputy Director, SJCRH
Director, Hartwell Center

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• 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 CenterHartwell Center -- ServicesServices
HighHigh--throughput DNA Sequencing & Genotypingthroughput DNA Sequencing & Genotyping
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Hartwell CenterHartwell Center -- ServicesServices
Macromolecular 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).

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Hartwell CenterHartwell Center -- ServicesServices
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
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Hartwell CenterHartwell Center -- ServicesServices
Functional 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.

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Hartwell CenterHartwell Center -- ServicesServices
Clinical 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 CenterHartwell Center -- ServicesServices
ProteomicsProteomics/Mass Spectrometry/Mass Spectrometry
• Services
– High-throughput protein identification.
• 2-D gel analysis
• Mass spectrometry
• Resources
– Instrumentation:
• ABI 494 cLC Procise ProteinSequencer.
• 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).

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Hartwell CenterHartwell Center -- ServicesServices
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 AffymetrixLIMS 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
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• 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 CenterHartwell Center -- ImpactImpact

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Hartwell CenterHartwell 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.
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Hartwell CenterHartwell Center -- SpaceSpace
High-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. ft
Administrative/office space 1000 sq. ft
Total 7,500 sq. ft.

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Hartwell CenterHartwell Center -- BudgetBudget
Budget FY 2000 FY 2001 FY 2002
Operating $3,427,026 $4,588,920 $5,236,664
Capital & Renovations 4,433,689 2,622,000 2,312,000
Indirect Costs 1,960,729 2,339,214 2,578,699
Subtotal 9,821,444 9,550,134 1 0 , 1 2 7 , 3 6 3
Less: Molecular Pathology (1,495,300) (1,063,496) (1,132,436)
Total Hartwell Center $8,326,144 $8,486,638 $8,994,927
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Hartwell CenterHartwell Center -- StaffStaff
• Clayton W. Naeve, P h. D .
• Clive Slaughter, P h. D .
• Brenda A l n e m y
• Krishna 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
• Perdeep Mehta, P h. D .
• Bill P a p p a s
• Matt S t i n e
• Karen R a k e s t r a w
• Margaret Cirtain
• Steven Turner
• Scott Olson
• A n u S a n k h a v a r a m
• Philip Poston, P h. D .
• Christpher Petucci, P h. D .
• Christine S h a m b l i n
• B o b Cassell
• Stephanie Tate
• D e a n n a N a e v e
• Lili Maleki
• Bill Lewis, P h. D .
• D i v y e n Patel, P h. D .
• Dawn Wilkins, P h.D.,Visiting Scientist
• Eric D u n c a v a g e, Intern
• Jennifer Campbell
• John Morris
• A s h u t o s h M i s h r a
• V i c k i Beal
• Patricia Ford
30 staff total, 7 Ph .D.s

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SummarySummary -- Key Elements to SuccessKey Elements to Success
• Strategic Planning
– 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.
• Attractive Career Path
– “Service” is not a pejorative word.
– Appropriate career ladder to attract and retain skilled staff.
• Integration of Key Technologies
– Depends on research environment.
– High -throughput biotechnologies likely required.
– Bioinformatics essential.
• Scientific Oversight
– 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.
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Hartwell Center Web SiteHartwell Center Web Site
http://www.hartwellcenter.org

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Thank You!