Biochemistry and Molecular Biology
Faculty of Medicine
Centre for High-Throughput Biology (CHiBi)
University of Lausanne, 1997, MD
University of Zurich, 2002, PhD (Biochemistry)
University of Cambridge, 2003, Post-doctoral fellow
Laboratory of Molecular Biology in Cambridge, 2006, MRC Research fellow
phone: 6048274731
phone: 6048274754
Michael Smith Laboratories Office 179
2185 East Mall
Vancouver, BC V6T 1Z4

Protein-DNA, protein-RNA and protein-protein interactions are fundamental to all biological processes. In recent years it has become possible, which the help of high-throughput methods, to discern the topology of large cellular interaction networks, which are represented as “interactome” maps. However, in order to understand cellular processes such as signal transduction, the relationship between cellular complexity and phenotype, and ultimately for being able to decipher the complex molecular mechanisms that underlie pathologies like cancer or neurodegeneration, we have not only to map the interactomes but also, and perhaps more importantly, elucidate how the structure and interaction properties of the constituent proteins affect network and phenotypic trait. Although NMR spectroscopy, X-ray crystallography and other biophysical methods have proven very successful in the determination of protein structures, the exhaustive characterization of all binary and higher-order protein complexes present in a cell is an extremely challenging task for several reasons. One of major importance is that a large fraction of eukaryotic proteins lack a predominant tertiary structure when in isolation. These so called natively or intrinsically disordered proteins (IDPs) can often adopt different folds when interacting with different partners. Importantly, IDPs are at the heart of various signaling and regulatory cascades in eukaryotic cells and altered abundance of IDPs is associated with severe disease conditions such as cancer or neurodegeneration.

We are interested in understanding the logic by which interactions that are mediated by IDPs can regulate complex cellular processes and how defects in interactions lead to disease.

Selected Publications

Heinkel F and Gsponer J (2015) “Determination of Protein Folding Intermediate Structures Consistent with Data from Oxidative Footprinting Mass Spectrometry” J. MOL. BIOL. in press

Zhao T, Wang Z, Cumberworth A, Gsponer J, de Freitas N and Bouchard A (2015) “Bayesian analysis of continuous time Markov chains with application to phylogenetic modeling” BAYESIAN ANAL. in press

Malhis N, Wong E, Nassar R and Gsponer J. (2015) “Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule” PLOS ONE in press

Cumberworth A, Bui J and Gsponer J. (2015) “Free energies of solvation in the context of protein folding: implications for implicit and explicit solvent models” J. COMP. CHEMISTRY in press

Albu RF, Chan GT, Zhu M, Wong ET, Taghizadeh F, Hu X, Mehran AE, Johnson JD, Gsponer J and Mayor T. (2015) “A feature analysis of lower solubility proteins in three eukaryotic systems” J. PROTEOMICS. 118, 21-38

Malhis N and Gsponer J. (2015) “Computational Identification of MoRFs in Protein Sequences” BIOINFORMATICS 31, 1738-1744

Na D, Son H and Gsponer J. (2014) “Categorizer: a tool that categorizes genes into user-defined
biological groups based on semantic similarity” BMC GENOMICS 15:1091

Fang N, Chan G, Zhu M, Comyn S, Persaud A, Deshaies R, Rotin D, Gsponer J and Mayor T. (2014) “Rsp5/Nedd4 is the major ubiquitin ligase that targets cytosolic misfolded proteins upon heat-stress” NATURE CELL BIOL. 16, 1227-1237

He C, Lamour G, Xiao A, Gsponer J and Li H. (2014) “Mechanically Tightening a Protein Slipknot into a Trefoil Knot.” J. AM. CHEM. SOC 136, 11946-11955

van der Lee R, Lang B, Kruse K, Gsponer J, Sánchez de Groot N, Huynen MA, Matouschek A, Fuxreiter M, and Babu M (2014) “Intrinsically disordered segments affect protein half-life in the cell and during evolution” CELL REPORTS 8,1832-1844

Lamour G, Kirkegaard JB, Li HB, Knowles TJP and Gsponer J (2014) “Easyworm: an open-source software tool to determine the mechanical properties of worm-like chains” SOURCE CODE BIOL MED 9:16

Bui JM and Gsponer J (2014) “Phosphorylation of an intrinsically disordered segment in Ets1 shifts conformational sampling toward binding-competent sub-states” STRUCTURE 22, 1196-1203

van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, Fuxreiter M, Gough J, Gsponer J, Jones DT, Kim PM, Kriwacki RW, Oldfield CJ, Pappu RV, Tompa P, Uversky VN, Wright PE and Babu MM (2014) “Classification of intrinsically disordered regions and proteins” ACS CHEMICAL REVIEWS 114, 6589-6631

Lamour G, Yip CK, Li H and Gsponer J (2014) “High Intrinsic Mechanical Flexibility of Mouse Prion Nanofibrils Revealed by Measurements of Axial and Radial Young’s Moduli.” ACS NANO 8, 3851-3861

Kristensen AR, Gsponer J, Foster LJ (2013) “Protein synthesis rate is the predominant regulator of protein expression during differentiation” MOL. SYSTEMS BIOLOGY 9:689

Ng AH, Fang NN, Comyn SA, Gsponer J, and Mayor T. (2013) “System-Wide Analysis Reveals Intrinsically Disordered Proteins are Prone to Ubiquitylation after Misfolding Stress.” MOL. CELL. PROTEOMICS 12, 2456-2467

Trudeau T, Nassar R, Cumberworth A, Wong ET, Woollard G and Gsponer J.(2013) “Structure and Intrinsic Disorder in Protein Autoinhibition.” STRUCTURE 21, 332-341

Gsponer J, Babu MM (2012) “Cellular Strategies for Regulating Functional and Nonfunctional Protein Aggregation” CELL REPORTS 2, 1425-1437

Kristensen AR, Gsponer J, Foster LJ (2012) “A high-throughput approach for measuring temporal changes in the interactome.” NATURE METHODS. 9, 907-909″


Further publications can be found here.

Further publications can be found here

Further publications can be found here