Nature

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Natures logistical solution

• Zoltan Maliga
• MPI-CBG
• CCSS International Worksop
• June 8-12, 2009

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Biology information, template, robust, adaptable
genetic blueprint
diversity
6 x 109 bases in the genome 20,000
proteins 10,000 found in all cells Robust
developmental program

• Trillions of cells
• Phenotypic archetypes
• Similar cognitive abilities

• common cell machinery
• cell-type specific genes

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Medicine Fixing a molecular network
Dosage-regime
Therapeutic
Toxicity
Death
No effect
In patients
COX-1
COX-2
Pain killer
Blood thinner
Stomach ulcers
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Can we look for control points in a process?
DNA
Tubulin
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Quality control subroutines ensure correct cell
division
DNA attached?
DNA separated?
Cell divided?
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Capitalizing on checkpoints to treat cancer
DNA
Tubulin
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Scaling in biology
Tubulin polymerization
Nutrient uptake, cell division
Cell movement, shape, organization
Forming connections between cells
Brain function, immunology, physiology
Reductionism Integrationism
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Exploring an infinite-parameter space
Predicted activity
genes
Function
processes
compartments
Interactions
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How is a cell physically organized?
parts list
neuron
brain
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Agents of cell organization Motor proteins in
cells
DNA
Tubulin
Actin
TUBULIN
ACTIN
What do they do? Where are they? What do they
bind?
40 motors walk on actin 39 motors walk on tubuliln
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Experimental system adding genes to cells
Gene (DNA)
GFP
Into cells
Localization
Interaction
Partner complex
INTEGRATE WITH CURATED DATA SETS
Gene
GFP
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Known motors are properly targeted in cell
division
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Each motor has a unique localization pattern
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A physical interaction map of the cell
Cell division
Virus infection Nutrient uptake Cell motion
Kidney disease Mitochondrial disease Mental
retardation
DNA alignment
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From data to function Understanding
mitochondria
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Motor labels moving strings in cells
MYO19 DNA
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Motor is not on filament 1
MYO19 Calnexin F-Actin
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Motor is on filament 2
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Motor surrounds mitochondria (generates energy)
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Maintaining mitochondria for energy production
branching
fission
fusion
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SUMMARY
Systematic analysis of all motor
proteins Different motor proteins define unique
compartments New discoveries on the control of
cell division Novel disease-relevant interaction
networks
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ACKNOWLEDGEMENTS
Mental Retardation Hilger Ropers (MPI-MG, Berlin)
Cell Division Helder Maiato Stefano Maffini (U.
Porto)
Cell Motility Anna Akhmanova (U. Erasmus)
Virology Beate Sodeik (U. Hannover)
Drug Mechanism Nathanael Gray (Harvard Medical
School) Merck, GmbH (Darmstadt)
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