NIAID and Global Health Research Resources for Tuberculosis

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1 NIAID and Global Health Research Resources for Tuberculosis Maria Y. Giovanni, Ph.D. Director, Office of Genomics and Advanced Technologies National Institute of Allergy & Infectious Diseases NIH/DHHS 2013

2 Slide Source: A. S. Fauci

3 Slide Source: A. S. Fauci

4 NIAID/DMID Genomics Program Sequencing Functional Genomics Proteomics Structural Genomics Systems Biology Genomic Sequencing Centers Functional Genomic Research Centers Clinical Proteomics Centers Structural Genomics Centers Systems Biology Centers Bioinformatics Resource Centers Bioinformatics Genomic Research Resources Genomic/Omics Data Sets, Databases, Bioinformatics Tools, Biomarkers, 3D Structures, Protein Clones, Predictive Models To address key questions in microbiology and infectious disease

5 NIAID Genomic Sequencing Centers for Infectious Diseases Sample Processing Method Develop High Throughput Sequencing Pipelines Metagenomics Transcriptomics Bioinformatics Tools Data Analysis Pipelines Genomics Bioinformatics Training

6 Chad Nussbaum Broad Institute

9 Knowledge from Data Challenge Rapidly expanding volume, complexity, and range of data Genome and Annotation RNA Sequencing Protein Expression Structure Isolates Subcellular Location Phenotype Exploit data to understand, prevent, diagnosis and treat infectious diseases

11 Building Bioinformatics Capacity for Infectious Diseases Community Provide integrated bioinformatics resources in support of basic and applied infectious diseases research. Data management, data sets, computational analysis tools, workspaces, web interfaces, and training

12 Collaborative Partnerships - Building resources with and for the community USG Agencies (USDA) B/M Gates Wellcome Trust NCBI TBDB ImmPort/IEDB Other Public Databases NIAID Research Programs Genome Seq Systems Biology Scientific community Data Users Data Producers

13 PATRIC Website (patricbrc.org) Bacterial Data Workflow Examples Personal Workspace Analysis Tools TB Site for TB data & Tools

14 Dynamic filtering by metadata values Metadata for Isolates

15 Protein Family Sorter Comparative Pathway Tool Disease View Genome Browser

16 NIAID Systems Approach to TB Combines genomic technology with computational methods to establish: Metabolic Network Model Regulatory Network Model

17 TB Regulatory Network Balázsi et al. (2008)

18 TB Regulatory Network 44 TB Transcription Factors 2008: 381 interactions 2012: 6429 interactions Transcription Factor Gene Sigma Factor ChIP Binding

NIAID Structural Genomics Centers for Infectious Diseases Goal: Provides the scientific community with 3D protein structures of targeted pathogenic proteins Features: Two Centers awarded in 2007:

19 NIAID Structural Genomics Centers for Infectious Diseases Goal: Provides the scientific community with 3D protein structures of targeted pathogenic proteins Features: Two Centers awarded in 2007: Northwestern University and Seattle Biomedical Research Institute Actively solicit requests for structure determination from the scientific community Protein targets are chosen by the Centers or proposed by external researchers Determine structures with important biological roles or those that show potential for vaccine or therapeutic development 1109 Structures deposited in the Protein Data Bank since 2007

marinum 252 23 M. paratuberculosis 232 13 M. smegmatis 289 27 M.

20 Mycobacterium strains Strain Total Targets Total Structures M. abscessus M. avium M. bovis 29 0 M. leprae M. marinum M. paratuberculosis M. smegmatis M. thermoresistibile M. tuberculosis M. Ulcerans Total

Resources for Researchers Product Development Pathway Basic Research Hypothesis Development and Testing Discovery Preclinical Development IDE- and IND-Enabling Activities Research Tools and

21 Resources for Researchers Product Development Pathway Basic Research Hypothesis Development and Testing Discovery Preclinical Development IDE- and IND-Enabling Activities Research Tools and Biological Materials Clinical Evaluation Trials Diagnostics Vaccines Therapeutics Research Tools and Technologies In vitro & in vivo testing & screening Therapeutic Development Services Biological Lead identification research & resources optimization (organisms and reagents) Chemistry & manufacturing, formulation, Clinical incl. GMP trials Biopharmaceutical development, incl. Basic and omics research resources Support GMP for clinical Nonclinical development, planning, & evaluation Vaccine Development Bioinformatics Services programs Preclinical and clinical services Testing & manufacturing, incl. GMP Biocontainment facilities Nonclinical & product development, planning & evaluation Regulatory activities & documentation Funding opportunities Research tools and biological materials to facilitate product development

g., licensed H1N1 treatment Candidate therapeutics e.g., optimization, synthesis, formulation, medicinal chemistry, product development plans; cgmp manufacture

22 Examples of Resources/Services Delivered Organisms Reagents e.g., proteins, antibodies, irradiated cells Assays e.g.,anthrax toxin neutralization assay Animal models e.g., plague antibiotic & vaccine models In vitro and in vivo screening for antimicrobial activity e.g., licensed H1N1 treatment Candidate therapeutics e.g., optimization, synthesis, formulation, medicinal chemistry, product development plans; cgmp manufacture

23 NIAID Diagnostic Program Emerging Technologies Early Stage Development Later Stage Development Sample Processing Targets Platform Dev Clinical Validation Assay Dev Integration Platform

24 Changing Landscape in Diagnostics High throughput next generation Sequencing Technologies AFB (acid fast bacilli) smear 454 GS FLX Illumina HiSeq 2000

25 Sample-to-Answer Multiplex Diagnostic Platforms

26 NanoString ncounter System Pejman Naraghi-Arani, LNLL Deb Hung, Broad Institute

27 Cepheid Gene Xpert System Sample in, answer out system Capable of detecting pathogen nucleic acid from a swab and in sputum, blood, urine samples David Alland, UMDNJ

NIAID Resources to Facilitate Medical Countermeasure Development

NIAID Resources to Facilitate Medical Countermeasure Development Paula Bryant, Ph.D. Senior Scientific Officer Concept Acceleration Program Biodefense, Research Resources, and Translational Research (OBRRTR)