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UNIVERSITY OF MICHIGAN
Alliance for Cellular Signaling(AfCS)
“Scaling up” academic science
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UNIVERSITY OF MICHIGAN
Collaboratory types
• Distributed research center– Large-scale, high-throughput academic/
industry hybrid
• Community data system– Unique model for motivating and
coordinating community contributions
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UNIVERSITY OF MICHIGAN
History• Success of human genome project
• NIH budget increase led to “Glue Grant” idea- scaling up science
• AfCS was the first glue grant, several others have followed
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UNIVERSITY OF MICHIGAN
History
• Al Gilman organized two meetings of signalling community at UTSW– Meeting #1: ~12 people
from UTSW– Meeting #2 ~ 30 people
• Funded started in 2000
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UNIVERSITY OF MICHIGAN
Scientific problem• AfCS is an
attempt to account for all signalling activity in a few model cells
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UNIVERSITY OF MICHIGAN
Scientific problem
• There are ~3,000 molecules that are potential ‘signals’ in a cell
• Interactions are complex and poorly understood
• “How do cells hear and interpret one voice when 50 are shouting (or mumbling)?”
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UNIVERSITY OF MICHIGAN
Distribution of funded participants
Molecular Biology Lab
Microscopy Lab
Bioinformatics Lab
Signaling Assays Lab
Protein Lab
Cellular Preparation
Antibody Lab
Systems Committee Lymphocyte
Alliance Labs
Systems Committee Myocyte
UT Southwestern
University of Washington
UCSD
Cal Tech
Stanford
BerkeleyUCSF
JHU
BCHarvard
Barbraham, UK
Steering Committee
SalkNashville
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UNIVERSITY OF MICHIGAN
Organization from Gilman, 2003
Technology Dev. Committee
Labs/ResourcesAdministration
Bioinformatics, data dissemination
Cell prep & analysis
Assay development
Molecular biology
ProteinsAntibodies
Microscopy
Signaling research community
SystemCommittees
Membership &Editorial Committee
Editorial board
Alliance members
Signaling database
Steering Committee
Bridging Projects
80%
5-10%40%100%
10%
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UNIVERSITY OF MICHIGAN
Resource diagram
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UNIVERSITY OF MICHIGAN
Products- Alliance Labs
• High quality data repository for the field- produced by labs
• IP policy dictates that data is open to everyone – AfCS labs (informally) excluded!
• Alliance members expected to do publishable analysis of this data
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UNIVERSITY OF MICHIGAN
Products- outside Alliance members
• Signalling Gateway– Co-published with Nature Publishing Group– Molecule pages-- 3,000 article reference
on every relevant molecule in the virtual cell
– Outside researchers recruited to write Molecule pages- equivalent to a journal review article
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UNIVERSITY OF MICHIGAN
Technology used• Email lists• Custom bioinformatics databases
– Developed at UCSD
• Polycom– Use application sharing– Supported by UTSW
• Reports • Annual meeting• Newsletters• Website • Web boards
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UNIVERSITY OF MICHIGAN
Use of Polycom• All PI’s have Viewstations in their offices
• Gilman uses as a replacement for the phone
• Used for all multi-site meetings, along with shared slides
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UNIVERSITY OF MICHIGAN
Motivations of participants
• Dis-incentives to be overcome:– No ownership of data- IP policy dictated
immediate publication – Little publication opportunity– Little distribution of individual credit
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UNIVERSITY OF MICHIGAN
Motivations of participants
• Professional bench staff– Experience useful in industry or med school– “Best of both worlds” academic and corporate
• Research staff - Lab directors, committee members– Chance to be involved in an innovative project– Lab improvement– Idiosyncratic motivations
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UNIVERSITY OF MICHIGAN
Motivations- community data system contributors
• Molecule pages are equivalent to a review article, but more structured and need to be updated yearly
• Co-published by Nature Publishing Group
• (Will these ‘count’ as academic publications?)
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UNIVERSITY OF MICHIGAN
Alliance successes to date
• IP policy• Recruitment of participants, members• Signalling gateway and ‘mini’ molecule
pages• Standardizing protocols• Bioinformatics infrastructure• Public antibody database, reagents,
protocols
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UNIVERSITY OF MICHIGAN
Protocols• Improvements in protocols due to need
for replication
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UNIVERSITY OF MICHIGAN
Challenges
• Specific target molecules being changed both to avoid problems and take advantage of new technology
• Aggregation of data yet to be attempted
• Relationship with outside authors still untested
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UNIVERSITY OF MICHIGAN
Outstanding questions:
• Will academic/ industry hybrid model be successful?
• Will CDS model (Molecule pages) be successful?
• Will other Glue grant projects succeed in similar projects with radically different organizational structures?