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.

Full Publication List


Selected Publications

  1. Skinnider MA, Acott ES, Prudova A, Kerr CH, Stonynoc N, Stancey RG, Chan QWT, Rattray D, Gsponer J and Foster LJ (2021) “An atlas of protein-protein interactions across mouse tissues” CELL 184(15):4073-4089.
  2. Necci M, Piovesan D; CAID Predictors; DisProt Curators, Tosatto SCE..(2021) “Critical assessment of protein intrinsic disorder prediction” NATURE METHODS 18(5):472-481. 
  3. Heinkel F, Abraham L, Ko M, Chao J, Bach H, Hui LT, Li H, Zhu M, Ling YM, Rogalski JC, Scurll J, Bui JM, Mayor T, Gold MR, Chou KC, Av-Gay Y, McIntosh LP and Gsponer J (2019) “Phase separation and clustering of an ABC transporter in Mycobacterium tuberculosis.” PROC. NATL. ACAD. SCI. USA 116, 16326-16331
  4. Malhis N, Jones SJM and Gsponer J (2019) “Improved measures for evolutionary conservation that exploit taxonomy distances.” NATURE COMMUNICATIONS 10, 1556 
  5. Malhis N, Jacobson M and Gsponer J (2016) “MoRFchibi SYSTEM: Software Tools for the Identification of MoRFs in Protein sequences” NUCLEIC ACIDS RESEARCH.  44(W1):W488-93

Further publications can be found here

Further publications can be found here