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NIH / NIGMS Perspective
Karin A. Remington, Ph.D., NIGMS
NCSA Strategic Planning Meeting
April 20, 2010
First Genome Sequenced 1995Haemophilus influenzae
1.8 million basepairs
Meta-GenomicsPilot Study:
The Sargasso Sea
Described in: Venter et al. Environmental Genome Shotgun
Sequencing of the Sargasso Sea, Science 304, 66-74 (2004)
Sorcerer ll ExpeditionSampling Sites
Sorcerer GOS Expedition34 sites, baseline of 150,000 sequences site
Just outside Canadian waterBrowns bankOutside HalifaxBedford BasinBay of FundeeTransit outside of MaineNewport Harbor, Rhode IslandBlock IslandCape MayNext To Nuke Power Plant in Delaware BayChesapeake Bay near Annapollis11.3 miles off of Nags Head N.C.South of Charleston S.COff Dry TortugasNorthwest of western most CubaYucatan Channel, MexicoCarribean Sea 30 nm of Rosario bank, Honduras80 nm north of Panama Canal
Borro de Colorado at STRI, Panama35 miles off of Panama City250 miles from Panama Canal30 miles from Coco's Island, EcuadorDirty Rock Coco's Island, EcuadorDevil's Crown Off of Floreana, GalapagosOff theCoast of Floreana, GalapagosEspumilla Beach, Santigo Island, GalapagosThermal Vent Roca Redonda, GalapagosOff Fernandina Island, Galapagos Floreana Flamingo Pond, GalapagosNorth Seamore Island, GalapagosWolf Island, GalapagosCabo Marshall, Isabella Island Galapagos
Challenges
Scalability (both memory and I/O) Flexible components, with incremental,
fault tolerant design Standardization so that studies can build
upon one another Changing definitions over time Visualization and usability
Comparative analyses of assemblies
GS05 GS04 GS06 GS02 GS03 GS08 GS07 GS09 GS10 GS00 GS14 GS25 GS01 GS31 GS16 GS15 GS34 GS29 GS27 GS30 GS21 GS22 GS19 GS17 GS23
North Atlantic
Comparative analyses of assemblies
Flamingo Pond (Galapagos)
Eastern US Seaboard
Galapagos
North Atlantic
Sargasso Sea andYucatan Channel, Mexico
Gulf Stream
Panama Canal
Comparative analyses of gene variationExample: proteorhodopsin
Plus 23 additional pages….
Comparative analyses of gene variationExample: proteorhodopsin
2 R01 GM 76667 5
Revolutionary and rapid changes in Science Increasing breadth of mission and growth Complex organization with many units
(27 institutes and centers, multiple program offices, e.g., OWHR, OAR, ORD, ...)
Structured by Disease, Organ, Life stage, Disciplines ….
Rapid Convergence of Science
21st Century Challenges for NIH
NIH: Many Compute Intensive Programs:
NIGMS Systems Biology Centers NCI Integrative Cancer Biology Program National Centers for Biomedical Computing (“Roadmap”) Intramural Systems Biology – NIAID, e.g. Coordinated Clinical Research Opportunities (via CTSAs, e.gg.) Various other programs…
decentralized, nascent, constantly in review
Models of Infectious Disease Agent Study
Computational and mathematical investigations of: Dynamics of emergence and spread of pathogens and
their products Identification and surveillance of infectious diseases Effectiveness and consequences of intervention
strategies Host/pathogen interactions Ecological, climatic, and evolutionary dimensions of
infectious diseases outbreaks.
Development of cutting edge computer science Translation of this computer science into biomedical
computation, i.e., effective algorithms and environments for solving real biological problems Enable the analysis, modeling, understanding, and
prediction of dynamic and complex biomedical systems across time and distance scales
Allow the integration of biomedical and behavioral data and knowledge at all levels of organization
National Centers for Biomedical Computing
(NCBCs)
Some NCBC Grand Challenges:
Automated shape analysis Knowledge resources that enhance
experimentation Integration of bioinformatics data and tools High-throughput sample acquisition, analysis
and identification Relationship between genomic and clinical data Multi-body dynamic simulation, modeling and
structural analysis
See detailed center information at http://ncbcs.org
NIGMS
Multiscale ModelingSpanning scales from molecular to population, designed to illuminate biological processes and further the predictive capability in biological, biomedical and environmental systems. Multi-scale modeling encompasses concepts of space, time and state space.
Genes Cellstructure-function
Tissue structure-function
Clinicalmedicine
Organ structure-function
ProteinsLipids
Carbohydra
tes
mRNA
…
30,000+genes
100,000+proteins
12 organsystems
1body
200+ celltypes
4 tissuetypes
Courtesy of Peter Hunter
Biological Scales
IMAG Multiscale Modeling (MSM) Consortium Working Groups
WG1 - Filament Dynamics and Simulation (FDS) WG2 - Cardiac and Skeletal Muscle Physiology WG3 - Macro-To-Micro Scale Transport in Human Systems WG4 - Cell Level Modeling WG5 - High Performance Computing, Computational Issues
and Algorithms WG6 - Tissue Mechanics WG7 - Multiscale Imaging WG8 – Theoretical Methods WG9 – Nano-modeling WG10 – Model Sharing
The CHALLENGES of finding funding at the NIH
NIGMS
A portrait of NIH Study Sections, when it comes to interdisciplinary teams and emerging areas:
To encourage fair review of the desired collaborations:
Special Emphasis Panels, for targeted FOAs Multiple PI applications Encouragement of “New” Investigators, with IC-
level policies to boost likelihood of funding “Enhancing Peer-Review” effort underway
NIH: some recent activities
NIH-wide IT infrastructure assessment NHGRI Cloud Computing workshop NCI/NIGMS Synthetic Biology workshop NHGRI Informatics and Analysis strategic planning National Centers for Biomedical Computing competitive renewal
Sequencing Bioinformatics
Eric Green account:
Enabling biology:We really need: to carefully design, document, and scrutinize
experiments to test hypotheses and avoid misinterpreting collected data
to rely less on automated annotation, and more on focused studies, and then create tools to assist
to integrate intra-organism and intra-community systems biology as well as hypothesis-generating and hypthothesis-testing systems biology
Human polymorphism