IBIC Summer Retreat Allen Institute Human Brain Atlas Allan R. Jones, PhD Chief Scientific Officer June 7, 2009
Jan 03, 2016
IBIC Summer RetreatAllen Institute Human Brain Atlas
Allan R. Jones, PhD
Chief Scientific Officer
June 7, 2009
Allen Institute for Brain Science: Fueling Discovery
• Who/what we are:– An independent, non-profit research organization working to support basic research in
the brain sciences (founded in 2001).
– Dedicated to making tools and information readily available to the scientific community
– Project-focused, milestone driven
– Multi-disciplinary teams working towards a common goal (math, physics, engineering, systems-level and molecular neuroscience, molecular biology, genetics, genomics, information technology)
– ~120 staff (30 PhDs)
– Located in 35000 sf of mixed lab/office space in the Fremont neighborhood of Seattle Washington
• What we are not:– A traditional, PI-driven research organization
– An extramural funding agency
The Allen Institute for Brain Science: Tools, resources, and data
Atlases: •Adult mouse brain (complete Sept. 2006)
•Mouse spinal cord (complete April 2009)
•Mouse development (complete March 2010)
• Human brain
•Phase 1 complete mid-2010
•Phase 2 complete in 2012
Projects:
•Sleep study (complete Dec. 2007)
•Genetic diversity study (complete May 2008)
• Human cortex survey (complete Sept. 2008)
•Human cortex population study/schizophrenia (complete Jan. 2009)
•Human Glioblastoma (complete April 2011 with possible extension)
Tools:
•Transgenic mouse drivers/reporters
•~20,000 unique visits per month across all projects (65% mouse brain, 10% human cortex, 10% development, 10% spinal cord, 5% sleep)•Atlas paper has been cited 260 times since publication in January 2007 (validation, discovery)
Connecting the “what” to the “where”
• We are quickly approaching a renaissance in our understanding of the basic genetic underpinnings of human biology and behavior
– Technology has enabled easy, cheap access to high resolution genetic data from humans. Large scale studies are underway
– Technology has provided ways to link functions in the brain to location
• Researchers that study genetics of human behavior and brain disease will be able to identify key genes
• Researchers that study brain function can already pinpoint brain locations that are altered or perform aberrantly in disease
• A key resource is needed to tie the “functional” maps with the “genetic” maps: a gene expression map of the human brain
Human Brain Atlas Overview: 2008-2012Multimodal atlas integrating gene expression and neuroanatomy
Phase 1: Anatomic resolution atlasAll structures:Comprehensively sample human brain
All genes:Microarray and sequence-based gene expression profiling
Phase 2: Cellular resolution atlasMost structures:High-resolution atlas of each structure
High-value genes: ISH for 50-500 genes/structure
Planning Phase 1: Microarray Data
2008 2009 2010 2011 2012
Planning Phase 2: ISH data
Protocol v 0.5 Status Check Initial data release Project completion
(Fresh brain images courtesy Mark Vawter and Preston Cartagena)
Section 1 mm of slab
Whole brain to microarray: serial divisionsWhole brain 5 mm coronal slabs Full coronal histology
Subdivide slab into 2x3 blocks
(subset of ~60 structures)
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IHC
IHCIH
CIH
CIS
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IHC
IHCIH
CIH
CL
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subcortex
cortex
Cryosection through 3 mm of 2x3 block Final 1 mm of block
gross dissection
1 cmsampling
0.5 cmsampling
MRI
~700 cortical samples
~300 subcortical samples
Macro-dissection (cortex)
2-10 human brain specimens
5 mm coronal slabs
Blockface images
6x8 histology, 2x3 histology, immunohistochemistry and in situ
hybridization (ISH)
Subdivided slab 2x3 blocks
Anatomic segmentations
User applications
MRI and DTI
Microarray analysis
LCM (sub-cortex)
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