background past research current and future work › 2013 › 02 › christoph_feinauer.pdf · esr...
TRANSCRIPT
BackgroundPast Research
Current and Future Work
ESR Presentation
Christoph Feinauer
03/02/2013
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
1 BackgroundUniversity Education
2 Past ResearchElectroporation PipettesZinc Finger Protein Modeling
3 Current and Future WorkProtein Residue Contact Inference by EvolutionaryInformationFuture DirectionsSecondments
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future WorkUniversity Education
1 BackgroundUniversity Education
2 Past ResearchElectroporation PipettesZinc Finger Protein Modeling
3 Current and Future WorkProtein Residue Contact Inference by EvolutionaryInformationFuture DirectionsSecondments
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future WorkUniversity Education
c©Google Maps
Country of origin:Germany
First part of diploma:Technical University ofMunichSecond part of diploma:University of HeidelbergMain Focus: BiophysicsNow: RiccardoZecchina’s group,Optimization andInference, Turin
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future WorkUniversity Education
c©Google Maps
Country of origin:GermanyFirst part of diploma:Technical University ofMunich
Second part of diploma:University of HeidelbergMain Focus: BiophysicsNow: RiccardoZecchina’s group,Optimization andInference, Turin
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future WorkUniversity Education
c©Google Maps
Country of origin:GermanyFirst part of diploma:Technical University ofMunichSecond part of diploma:University of Heidelberg
Main Focus: BiophysicsNow: RiccardoZecchina’s group,Optimization andInference, Turin
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future WorkUniversity Education
c©Google Maps
Country of origin:GermanyFirst part of diploma:Technical University ofMunichSecond part of diploma:University of HeidelbergMain Focus: Biophysics
Now: RiccardoZecchina’s group,Optimization andInference, Turin
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future WorkUniversity Education
c©Google Maps
Country of origin:GermanyFirst part of diploma:Technical University ofMunichSecond part of diploma:University of HeidelbergMain Focus: BiophysicsNow: RiccardoZecchina’s group,Optimization andInference, Turin
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
1 BackgroundUniversity Education
2 Past ResearchElectroporation PipettesZinc Finger Protein Modeling
3 Current and Future WorkProtein Residue Contact Inference by EvolutionaryInformationFuture DirectionsSecondments
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Electroporation Pipettes
Andreas T. SchaeferGroup, BehaviouralNeurophysiologyMax Planck Institute forMedical Resarch,Heidelberg
Main contributor:Daniel Schwarz
Olfactory Bulb
http://en.wikipedia.org/wiki/File:Gray772.png
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Electroporation Pipettes
Andreas T. SchaeferGroup, BehaviouralNeurophysiologyMax Planck Institute forMedical Resarch,HeidelbergMain contributor:Daniel Schwarz
Olfactory Bulb
http://en.wikipedia.org/wiki/File:Gray772.png
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Electroporation Pipettes
Andreas T. SchaeferGroup, BehaviouralNeurophysiologyMax Planck Institute forMedical Resarch,HeidelbergMain contributor:Daniel Schwarz
Olfactory Bulb
http://en.wikipedia.org/wiki/File:Gray772.png
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Membrane poration bytransmembranepotential
Useless for networktracing
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Membrane poration bytransmembranepotential
Useless for networktracing
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
New pipette design
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
New pipette design
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
New pipette design
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Reliable labeling of about 80 percent in the glomerulus
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
1 BackgroundUniversity Education
2 Past ResearchElectroporation PipettesZinc Finger Protein Modeling
3 Current and Future WorkProtein Residue Contact Inference by EvolutionaryInformationFuture DirectionsSecondments
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Zinc Finger Proteins
D.W. Heermann Group,Statistical Physics andTheoretical Biophysics,ITP Heidelberg
Chromatin folding: from biology to polymer modelsand back Mariliis Tark-Dame, Roel van Driel, DieterW. Heermann, 2011 J Cell Sci 124, 839-845
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Zinc Finger Proteins
D.W. Heermann Group,Statistical Physics andTheoretical Biophysics,ITP Heidelberg
Chromatin folding: from biology to polymer modelsand back Mariliis Tark-Dame, Roel van Driel, DieterW. Heermann, 2011 J Cell Sci 124, 839-845
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
1D Lattice Model for Zinc Finger Protein Binding
CTCF: 11-Zinc FingerProtein, Involved inDNA looping
Figure: MacPherson, M. J., Sadowski, P. D. TheCTCF insulator protein forms an unusual DNAstructure. BMC molecular biology 11, 101 (2010).
Thesis: The Effect of Flexible Linkers on the BindingAffinity and the Binding Distribution of Zinc FingerProteins
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
1D Lattice Model for Zinc Finger Protein Binding
CTCF: 11-Zinc FingerProtein, Involved inDNA looping
Figure: MacPherson, M. J., Sadowski, P. D. TheCTCF insulator protein forms an unusual DNAstructure. BMC molecular biology 11, 101 (2010).
Thesis: The Effect of Flexible Linkers on the BindingAffinity and the Binding Distribution of Zinc FingerProteins
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
{
DNA Binding Unit
Protein Domain
1-Domain Version Bound2-Domain Version Bound
Flexible Linker
Rigid Linker
{ Allowed States
Forbidden States
(Disordered Domains)(Gap)
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Increased non-specific binding affinity throughdomains
1 2 4 8 1610
−10
10−9
10−8
10−7
10−6
Domains
Bin
din
g A
ffin
ity
Chemical Potential µ = 25kbT
0.0kbT
−0.01kbT
−0.05kbT
−0.1kbT
−0.15kbT
1 2 4 8 1610
−8
10−7
10−6
10−5
10−4
Domains
Bin
din
g A
ffin
ity
Chemical Potential µ = 20kbT
0.0kbT
−0.01kbT
−0.05kbT
−0.1kbT
−0.15kbT
1 2 4 8 1610
−6
10−5
10−4
10−3
10−2
Domains
Bin
din
g A
ffin
ity
Chemical Potential µ = 15kbT
0.0kbT
−0.01kbT
−0.05kbT
−0.1kbT
−0.15kbT
1 2 4 8 1610
−4
10−3
10−2
10−1
100
Domains
Bin
din
g A
ffin
ity
Chemical Potential µ = 10kbT
0.0kbT
−0.01kbT
−0.05kbT
−0.1kbT
−0.15kbT
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Influence of an increased non-specific binding energyon binding characterstics
Square Potential
3 Domains Bound
2 Domains Bound
2 Domains Bound
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Electroporation PipettesZinc Finger Protein Modeling
Christoph J. Feinauer, Andreas Hofmann, SebastianGoldt, Lei Liu, Gabriell Mate, Dieter W. Heerman. ZincFinger Proteins and the 3D Organisation ofChromosomes, Advances in Protein Chemistry andStructural Biology, accepted 2012
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
1 BackgroundUniversity Education
2 Past ResearchElectroporation PipettesZinc Finger Protein Modeling
3 Current and Future WorkProtein Residue Contact Inference by EvolutionaryInformationFuture DirectionsSecondments
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Protein Residue Contact Inference by EvolutionaryInformation
A mutation in a proteinresidue leads to achanged evolutionarypressure in proteinresidues with which it isin contact
Sequence data →predicted residuecontacts
Figure: Marks et al. Protein structure prediction from sequence variation. Nature biotechnology 30, (2012).
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Protein Residue Contact Inference by EvolutionaryInformation
A mutation in a proteinresidue leads to achanged evolutionarypressure in proteinresidues with which it isin contact
Sequence data →predicted residuecontacts
Figure: Marks et al. Protein structure prediction from sequence variation. Nature biotechnology 30, (2012).
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Several approaches exist:
1 Mutual Information Dunn et al. Mutual information without the influence of
phylogeny or entropy dramatically improves residue contact prediction. Bioinformatics
(2008)
2 Direct Coupling Analysis Morcos, F. et al. Direct-coupling analysis of
residue coevolution captures native contacts across many protein families. Proceedings of
the National Academy of Sciences of the United States of America 108 (2011)
3 Correlated Changes in inferred Phylogenetic TreesMiyazawa, S. Prediction of Contact Residue Pairs Based on Co-Substitution between Sites in
Protein Structures. PLoS ONE 8 (2013)
4 Bayesian InferenceBurger L, van Nimwegen E (2010) Disentangling direct from
indirect co- evolution of residues in protein alignments. PLoS Comp Biol 6: e1000633.i
⇒ Write a Review
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Several approaches exist:1 Mutual Information Dunn et al. Mutual information without the influence of
phylogeny or entropy dramatically improves residue contact prediction. Bioinformatics
(2008)
2 Direct Coupling Analysis Morcos, F. et al. Direct-coupling analysis of
residue coevolution captures native contacts across many protein families. Proceedings of
the National Academy of Sciences of the United States of America 108 (2011)
3 Correlated Changes in inferred Phylogenetic TreesMiyazawa, S. Prediction of Contact Residue Pairs Based on Co-Substitution between Sites in
Protein Structures. PLoS ONE 8 (2013)
4 Bayesian InferenceBurger L, van Nimwegen E (2010) Disentangling direct from
indirect co- evolution of residues in protein alignments. PLoS Comp Biol 6: e1000633.i
⇒ Write a Review
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Several approaches exist:1 Mutual Information Dunn et al. Mutual information without the influence of
phylogeny or entropy dramatically improves residue contact prediction. Bioinformatics
(2008)
2 Direct Coupling Analysis Morcos, F. et al. Direct-coupling analysis of
residue coevolution captures native contacts across many protein families. Proceedings of
the National Academy of Sciences of the United States of America 108 (2011)
3 Correlated Changes in inferred Phylogenetic TreesMiyazawa, S. Prediction of Contact Residue Pairs Based on Co-Substitution between Sites in
Protein Structures. PLoS ONE 8 (2013)
4 Bayesian InferenceBurger L, van Nimwegen E (2010) Disentangling direct from
indirect co- evolution of residues in protein alignments. PLoS Comp Biol 6: e1000633.i
⇒ Write a Review
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Several approaches exist:1 Mutual Information Dunn et al. Mutual information without the influence of
phylogeny or entropy dramatically improves residue contact prediction. Bioinformatics
(2008)
2 Direct Coupling Analysis Morcos, F. et al. Direct-coupling analysis of
residue coevolution captures native contacts across many protein families. Proceedings of
the National Academy of Sciences of the United States of America 108 (2011)
3 Correlated Changes in inferred Phylogenetic TreesMiyazawa, S. Prediction of Contact Residue Pairs Based on Co-Substitution between Sites in
Protein Structures. PLoS ONE 8 (2013)
4 Bayesian InferenceBurger L, van Nimwegen E (2010) Disentangling direct from
indirect co- evolution of residues in protein alignments. PLoS Comp Biol 6: e1000633.i
⇒ Write a Review
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Several approaches exist:1 Mutual Information Dunn et al. Mutual information without the influence of
phylogeny or entropy dramatically improves residue contact prediction. Bioinformatics
(2008)
2 Direct Coupling Analysis Morcos, F. et al. Direct-coupling analysis of
residue coevolution captures native contacts across many protein families. Proceedings of
the National Academy of Sciences of the United States of America 108 (2011)
3 Correlated Changes in inferred Phylogenetic TreesMiyazawa, S. Prediction of Contact Residue Pairs Based on Co-Substitution between Sites in
Protein Structures. PLoS ONE 8 (2013)
4 Bayesian InferenceBurger L, van Nimwegen E (2010) Disentangling direct from
indirect co- evolution of residues in protein alignments. PLoS Comp Biol 6: e1000633.i
⇒ Write a Review
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Several approaches exist:1 Mutual Information Dunn et al. Mutual information without the influence of
phylogeny or entropy dramatically improves residue contact prediction. Bioinformatics
(2008)
2 Direct Coupling Analysis Morcos, F. et al. Direct-coupling analysis of
residue coevolution captures native contacts across many protein families. Proceedings of
the National Academy of Sciences of the United States of America 108 (2011)
3 Correlated Changes in inferred Phylogenetic TreesMiyazawa, S. Prediction of Contact Residue Pairs Based on Co-Substitution between Sites in
Protein Structures. PLoS ONE 8 (2013)
4 Bayesian InferenceBurger L, van Nimwegen E (2010) Disentangling direct from
indirect co- evolution of residues in protein alignments. PLoS Comp Biol 6: e1000633.i
⇒ Write a Review
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Future Directions
Combinations of Methods should be possible
Protein-Protein Networks
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Future Directions
Combinations of Methods should be possibleProtein-Protein Networks
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
Secondments
La SapienzaKTH, Stockholm
Christoph Feinauer ESR Presentation
BackgroundPast Research
Current and Future Work
Protein Residue Contact Inference by Evolutionary InformationFuture DirectionsSecondments
The End
Thank you for your attention!
Christoph Feinauer ESR Presentation