Member Profile
Christina Kiel
Biography
RESEARCH INTERESTS
Determining protein protein interaction (PPI) networks and predicting network changes in time and change are crucial for understanding and modeling biological systems and signal transduction pathways. During the past few years in Luis Serrano’s group, I have used a combination of experimental and computational tools, in particular structural information towards reaching this goal (reviewed in Kiel et al, 2008; Van der Sloot et al, 2009; Kiel et al, 2010).
Computational tools include methods to predict protein interactions based on structural homology (homology modeling) and energy calculations using the protein design algorithm FoldX (www.foldx.crg.es/). Experimental verification was done using protein expression and purification, pull-down experiments and biophysical measurements, such as isothermal titration calorimerty (ITC) and surface plasmon resonance (SPR). In addition, I used structural information in combination with computational tools to estimate equilibrium and kinetic constants. Further, structural information and protein design was used to perturb selected nodes in a signaling cascade, computer simulations were used to predict the effect on the downstream signaling output, and predictions were experimentally validated in cell culture time course experiments (Kiel & Serrano, Sci Signal, 2009).
Currently, we are aiming at a complete quantitative understanding of a selected signal transduction pathway (epidermal growth factor receptor signaling) in three different cells types. Towards reaching this goal, we are determining absolute protein concentrations, protein localization, and we incorporate time, space and structural information.
Resume
CV
Work experience
Since 01.10.2006: Staff Scientist, laboratory of Prof. Luis Serrano, Department of Systems Biology. CRG Centre de Regulacio Genomica, Dr Aiguader 88, 08003 Barcelona, Spain.
Research on experimental and computational signal transduction, computer modelling, protein design, epidermal growth factor signal transduction, and rhodopsin signaling,
01.11.2003 - 30.09.2006: PostDoc, laboratory of Prof. Luis Serrano, Department of Department of Structural and Computational Biology. EMBL Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany.
Research on protein design, engineering, computer modelling, Ras effector interactions.
01.07.2003- 31.10.2003: PostDoc, laboratory of Prof. Alfred Wittinghofer, Department of Structural Biology. Max-Planck-Institute for Molecular Physiology, Otto-Hahn Str. 11, 44227 Dortmund, Germany.
Research on protein-protein interactions, energy landscapes, thermodynamic and kinetic characterization of Ras effector interactions.
Education and training
01.01.2000 - 30.06.2003: PhD thesis at the Max-Planck-Institute for Molecular Physiology, Dortmund, Germany, Department of Structural Biology (Prof. Alfred Wittinghofer/ Dr. Christian Hermann). Title: “Design and investigation of Ras/effector interactions with changed electrostatic properties”.
06.1999-12.1999: Diploma thesis at the Max-Planck-Institute for Molecular Physiology, Department of Structural Biology, Dortmund, Germany (Prof. Alfred Wittinghofer/ Dr. Christian Hermann). Title: “Thermodynamic analysis of Ras and Rap interacting with RalGDS”.
1993-1999: Study of Biochemistry. Ruhr-University Bochum, Germany.
Publications and book chapters
Kiel C, Serrano L. Challenges ahead in signal transduction: MAPK as an example. Curr Opin Biotechnol, in press, 2011.
Kiel C,* Vogt A,* Campagna A,* Chatr-aryamontri A, Swiatek-de Lange M, Beer M, Cesareni G, Serrano L, Ueffing M. Structural and functional protein network analysis predicts novel signaling functions for rhodopsin. Molecular Systems Biology, in press, 2011. (*equal author contribution)
Rakoczy EP,* Kiel C,* McKeone R, Stricher F, Serrano L. Analysis of Disease-Linked Rhodopsin Mutations Based on Structure, Function, and Protein Stability Calculations. J Mol Biol 405: 584-606, 2011. (*equal author contribution)
Kiel C, Yus E, Serrano L. Engineering signal transduction pathways. Cell 140: 33-47, 2010. (Review)
Kiel C, Filchtinski D, Spoerner M, Schreiber G, Kalbitzer HR, Herrmann C. Improved binding of raf to Ras.GDP is correlated with biological activity. J Biol Chem 284: 31893-902, 2009.
Kiel C, Serrano L. Cell type-specific importance of ras-c-raf complex association rate constants for MAPK signaling. Sci Signal 2(81):ra38, 2009.
Van der Sloot AM, Kiel C, Serrano L, Stricher F. Protein design in biological networks: from manipulating the input to modifying the output. Protein Eng Des Sel 22: 537-42, 2009. (Review)
Markson G, Kiel C, Hyde R, Brown S, Charalabous P, Bremm A, Semple J, Woodsmith J, Duley S, Salehi-Ashtiani K, Vidal M, Komander D, Serrano L, Lehner P, Sanderson CM. Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Genome Res 19: 1905-11, 2009.
Kiel C, Serrano L. The impact of structural proteomics on the prediction of protein-protein interactions. Published in “Structural proteomics and its impact on the life sciences”, edited by Sussman JL and Silman I, World Scientific, 2008. (Book chapter)
Kiel C, Aydin D, Serrano L. Association rate constants of ras-effector interactions are evolutionarily conserved. PLoS Comput Biol 4: e1000245, 2008.
Kiel C, Beltrao P, Serrano L. Analyzing protein interaction networks using structural information. Annu Rev Biochem 77: 415-41, 2008. (Review)
Campagna A, Serrano L, Kiel C. Shaping dots and lines: adding modularity into protein interaction networks using structural information. FEBS Lett 582(8):1231-6, 2008. (Review)
Kiel C, Serrano L. Prediction of Ras-effector interactions using position energy matrices. Bioinformatics 23(17):2226-30, 2007.
Beltrao P, Kiel C, Serrano L. Structures in systems biology. Curr Opin Struct Biol 17: 378-84, 2007. (Review)
Kiel C, Foglierini M, Kuemmerer N, Beltrao P, Serrano L. A genome-wide Ras-effector interaction network. J Mol Biol 370: 1020-32, 2007.
Kiel C, Serrano L. Affinity can have many faces: Thermodynamic and kinetic properties of Ras effector complex formation. Curr Chem Biol 1: 215-225, 2007.
Kiel C, Serrano L. The ubiquitin domain superfold: structure-based sequence alignments and characterization of binding epitopes. J Mol Biol 355: 821-44, 2006.
Kiel C, Wohlgemuth S, Rousseau F, Schymkowitz J, Ferkinghoff-Borg J, Wittinghofer F, Serrano L. Recognizing and defining true Ras binding domains II: in silico prediction based on homology modelling and energy calculations. J Mol Biol 348(3):759-75, 2005.
Wohlgemuth S,* Kiel C,* Krämer A, Serrano L, Wittinghofer F, Herrmann C. Recognizing and defining true Ras binding domains I: biochemical analysis. J Mol Biol 2005 348(3):741-58, 2005. (*equal author contribution)
Kiel C, Serrano L, Herrmann C. A detailed thermodynamic analysis of ras/effector complex interfaces. J Mol Biol 340(5):1039-58, 2004.
Kiel C, Selzer T, Shaul Y, Schreiber G, Herrmann C. Electrostatically optimized Ras-binding Ral guanine dissociation stimulator mutants increase the rate of association by stabilizing the encounter complex. Proc Natl Acad Sci U S A 101(25):9223-8, 2004.
Gohlke H, Kiel C, Case DA. Insights into protein-protein binding by binding free energy calculation and free energy decomposition for the Ras-Raf and Ras-RalGDS complexes. J Mol Biol 330(4):891-913, 2003.
Ahmadian MR, Kiel C, Stege P, Scheffzek K. Structural fingerprints of the Ras-GTPase activating proteins neurofibromin and p120GAP. J Mol Biol 329(4):699-710, 2003.
Linnemann T, Kiel C, Herter P, Herrmann C. The activation of RalGDS can be achieved independently of its Ras binding domain. Implications of an activation mechanism in Ras effector specificity and signal distribution. J Biol Chem 277(10):7831-7, 2002.
Kiel C, Herrmann C. Double mutant cycle analysis of Ras proteins and their effectors: Quantification of binding specificity. Published in “Protein Modules in Cellular Signaling”, edited by Heilmeyer L and Friedrich P, IOS Press, 2001. (Book chapter)
Invited talks
Spetses Protein Science Summer School 2011. Talk: “Systems Analysis of EGFR Signal Processing by Combining 3D Structures, Protein Quantification and Reverse Arrays”. Spetses, Greece, June 1-8, 2011.
12th Annual Congress of SocBin – Society for Bioinformatics in the Nordic Countries. Talk: “Integration of networks with disease-linked mutations based on structure, function, and protein stability calculations”. Helsinki, Finland, May 10-12, 2011.
IV Congress of the Spanish Proteomic Society SEPROT 2011. Talk: “Combining 3D structures with protein quantification to understand cell type specific epidermal growth factor receptor signal processing”. Segovia, Spain, February 8-11, 2011.
6th Workshop Molecular Interactions: From Units to Systems. Talk: “Structures and data integration in signal transduction”. Berlin, Germany, September 15-17, 2010.
Workshop (SPINE, MPLEXES, 3D repertoire): What is a macromolecular complex? Shades of meaning across cellular, systems, and structural biology. Talk: “Structural systems biology approaches to study signal transduction involving Ras-effector interactions”. Amsterdam, Netherlands, October 1-2, 2009.
CNRS – Conference Jaques Monod: Regulation and function of small GTPases. Talk:“Structural systems biology approaches to study signal transduction involving Ras-effector interactions. Aussois, France, June 17-21, 2009.
Ramón Areces symposium: Ras superfamily proteins: regulation, effectors, and participation in human disease. Talk: “Cell-type specific importance of Ras-cRaf kinase complex association rate constants for MAP kinase signalling”. Salamanca, Spain, May 18-19, 2009.
Seminar in Prof. M. Ueffing group, GSF, Munich, November Retreat. Talk: “Prediction of protein-protein interactions based on structural information”. Reimlingen, Germany, November 7-9, 2007.
Joint RTK consortium & BSPR & EBI 2007 Workshop: Proteomics and phosphoproteomics of receptor tyrosine (RTK) signaling networks. Talk: “Protein design as a tool for dissecting signal transduction pathways. Hinxton Hall Conference Centre, Cambridge, UK, July 23-24, 2007.
International Workshop: Physical and Chemical Foundations of Bioinformatics Methods. Talk: “Prediction of protein-protein interactions based on structural information”. Dresden, Germany, June 18-22, 2007.
Seminar in Prof. A. Wittinghofer group, Max-Planck Institute Dortmund, Department of Structural Biology. Talk: “Combining computational and biochemical tools to analyze biological systems”. Dortmund, Germany, September 15, 2006.
17th IUPAC Conference on Chemical Thermodynamics. Talk: “Energy Landscapes of proteins: Thermodynamic and kinetic properties of Ras/Effector interfaces”. Rostock, Germany, July 28-August 2, 2002.
Graduate School of Chemistry and Biochemistry. Talk: “Energy Landscapes of proteins: Thermodynamic and kinetic properties of Ras/Effector interfaces”. Bielefeld, Germany, July 4-5, 2002.
Seminar in Prof. Rob C. Aalberse group, Sanquin Research at CLB, Department of Immunopathology. Talk: “Energy Landscapes of proteins: Thermodynamic and kinetic properties of Ras/Effector interfaces”. Amsterdam, Netherlands, May 6, 2002.
Participation in international conferences, workshops and summer schools
The EMBO meeting 2010. Poster: “Systems Biology Analysis of the Epidermal Growth Factor Signal Transduction Pathway: From Structures to Data Integration”. Barcelona, Spain, September 4-7, 2010.
First EMBL/CRG Systems Biology Workshop: The Evolution of Biological Networks. Barcelona, Spain, July 12-13, 2010.
Proteomic Forum 2009. Berlin, Germany, March 29-April 2, 2009.
The 9th International Conference on Systems Biology. Poster: “Structure-based design, Computer Simulations, and in vivo analysis of Ras-Raf Mutant complexes with changed kinetic properties and affinities”. Gothenburg, Sweden, August 23-27, 2008.
2nd International Conference on Molecular Perspectives on Protein-Protein Interactions. Poster: “Structure-based design, Computer Simulations, and in vivo analysis of Ras-Raf Mutant complexes with changed kinetic properties and affinities”. Dubrovnic, Croatia, June 27-July 1, 2008.
Complex Modelling Course. EMBL-Heidelberg. Heidelberg, Germany, July 5-6, 2007.
VIth European Symposium of The Protein Society. Poster: “Genome wide prediction of Ras effector interactions”. Barcelona, Spain, April 30-May 4, 2005.
56. Mosbacher Kolloquium: Molecular Machines. Mosbach, Baden, March 31-April 2, 2005.
HUPO 3rd Annual World Congress. Poster: ”Prediction of protein-protein interactions based on sequence and structure”. Beijing, China, October 25-27, 2004.
Structural Biology at Crossroads: From Biological Molecules to Biological Systems. EMBL (DESY) Hamburg. Poster: “Prediction of protein-protein interactions based on sequence and structure”. Hamburg, September 15-18, 2004.
3D SIG: Structural Bioinformatics Special Interest Meeting. Poster: “Prediction of protein-protein interactions based on structure”. Glasgow, Scotland, UK, July 29-30, 2004.
FASEB Summer Research Conferences: Regulation and Biological Function of Small GTPases. Poster: “Prediction of Ras-effector interactions based on sequence and structure”. Snowmass, Colorado, USA, July 10-15, 2004.
GBM Herbsttagung. Poster: “Thermodynamic, Kinetic and structural Analysis of Ras Proteins and their Effectors”. Bochum, Germany, September 9-12, 2001.
Biocalorimetry 2001 Conference: Current Trends in Microcalorimetry. Poster: “Thermodynamic, Kinetic and structural Analysis of Ras Proteins and their Effectors”. Philadelphia, USA, July 26-28, 2001.
Second International Symposium on Structures and Mechanism in Biological Signal and Energy Transduction. Poster: “Thermodynamic, Kinetic and structural Analysis of Ras Proteins and their Effectors”. Dabringhausen, Germany, November 23-25, 2000.
Workshop: Fundamentals of BioCalorimetry. Franfurt, Germany, October 27, 2000.
NATO/FEBS Advanced Study Institute International Summerschool: Protein Modules in cellular Signaling. Poster and short talk: ”Analysis of the H-Ras-RalGDS/Raf Interface by Double Mutant Cycles”. St. Martin de Londres, France, September 13-22, 2000.
51. Mosbacher Kolloquium. GTP-Binding Proteins: Central Regulators in Cell Biology. Poster: “Analysis of the H-Ras-RalGDS/Raf Interface by Double Mutant Cycles”. Mosbach, Baden, Germany, April 3-5, 2000.
SFB394 Symposium. Hamminkeln-Dingden, Germany, December 10-11, 1999.
2nd International Conference on Applications of Biocalorimetry. Halle/Saale, Germany, March 28-31, 1999.
National meetings
19. Rabenstein Kolleg. Short talk: “Kinetische Kontrole der Signalweiterleitung ueber Ras-Proteine”. Weissenstadt, Germany, June 14-16, 2001.
18. Rabenstein Kolleg. Short talk: “Detaillierte Analyse der Interaktion von H-Ras and Rap1A mit RalGDS”. Pottenstein, Germany, June 22-24, 2000.
17. Rabenstein Kolleg. Pottenstein, Germany, June 3-5, 1999.
Group Members
