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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)
Nis sl
Nis sl
Nis
sl
My
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in
My
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Mye
lin IHC
IHC
IHCIH
CIH
CIS
H
Nis sl
Nis sl
Nis
sl
My
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in
My
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in
Mye
lin IHC
IHC
IHCIH
CIH
CL
CM
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)
(a)
(d)
(b) (c)
(e) (f)
(g) (h)(i)
(j)
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