Assaf Zaritsky
Decoupling global
biases and local
interactions between
cell biological
variables
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Quantifying protein-protein co-localization
Dunn et al. (2011)
Red Green
Merge
Condition B
Condition A
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What additional information is
hidden in co-localization data?
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Co-orientation of intracellular
cytoskeletal networks in
migrating cells
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Vimentin provides a structural template
for microtubule growth
Gan, Ding and Burckhardt et al. (2016)
Genome-edited Retinal Pigment
Epithelial (RPE) cells
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A relation between cell polarity and
vimentin-microtubule interaction?
Zhuo Gan
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Polarity-independent interaction of
vimentin and microtubules
?
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Polarity-independent interaction of
vimentin and microtubules
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What do we want to achieve?
• Simultaneous investigation of mechanisms that drive
global bias and local interactions
How?
• By modeling the observed agreement between
matched variables as the cumulative global and local
components
Observed
colocalization
= Global bias +
Local
interaction
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DeBias
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DeBias
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DeBias
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DeBias
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DeBias
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DeBias
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Polarity-independent interaction of
vimentin and microtubules
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Polarity-independent interaction of
vimentin and microtubules
Global index
Local index
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Global bias: cell polarity
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Inferring co-localization and
predicting dynamics from fixed
cells during clathrin-mediated
endocytosis (CME)
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Maturation of a clathrin coated pit
Marcel Mettlen
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Cross-talk between signaling
receptors (AKT) and components of
the endocytic machinery
Carlos Reis, H1299 cells
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Inferring co-localization and predicting
dynamics from fixed cells during
clathrin-mediated endocytosis (CME)
Global index
Local index
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Global bias: reduced TfnR in CCPs
upon Akt inhibition
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More CCPs containing less TfnR alter
CCPs dynamics upon AKT inhibition
Reduced TfnR in CCPs upon Akt inhibition increased short-lived,
(most likely) abortive events decrease in CME efficiency
Live imaging Internalization
Fixed imaging
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Global bias: more CCPs with less
TfnR upon Akt inhibition
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Spatio-temporal co-localization of Rac1 and Vav1
activity in a migrating cell (With Dan Marston, UNC)
Take home message
DeBias enables identifying the gorilla
Simons and Chabris (1999)
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Uri
Obolski,
(Theory)
Carlos
Reis
(Endocytosis)
Zhuo
Gan,
(Vimentin, PKC)
Yi
Du
(Webserver)
Gaudenz
Danuser
Liya
Ding
Liqiang
Wang
Tamal
Das
Joachim
Spatz
Christoph
Burckhardt
Acknowledgments
Sandy
Schmid