Joerg Gsponer

Profile Details

Position/Role

Faculty

Affiliation

Biochemistry & Molecular Biology

Website

http://www.chibi.ubc.ca/faculty/gsponer/labhome

Phone

gsponer [at] chibi.ubc.ca

Research Interests

Protein-DNA, protein-RNA and protein-protein interactions are fundamental to all biological processes, and a comprehensive determination of all these interactions that can take place in an organism provides a framework for understanding biology as an integrated system. 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 synthesis and turnover of the constituent macromolecules as well as changes of their structure and interaction potential affect the network properties and ultimately the phenotypic trait.

We are interested in the development and application of new computational techniques that make use of experimental data –originating from protein engineering experiments to high-throughput screens – in order to gain a better understanding of (i) the folding and interaction mechanisms of signaling proteins and (ii) how signalling-specific structural features constrain their evolvability, regulation and interaction in eukaryotic cells.

In our research, we are also addressing questions related to protein misfolding and aggregation. Protein aggregation and amyloid formation have been linked to a variety of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease or Creutzfeldt-Jakob disease. We are developing new computational approaches to study protein aggregation and predict the structure proteins adopt in amyloid fibrils. Using high-throughput screening methods, we further aim at understanding which protein-protein interactions are affected in neurodegenerative disorders such as Huntington's or Creutzfeldt-Jakob disease, and more specifically, which signaling pathways most perturbed.

Selected Publications

Signaling protein structure and function

Friel C.T., Smith A.D., Vendruscolo M., Gsponer J. and Radford S. E. (2009), “An atomistic view of an evolutionarily conserved folding landscape.” NAT. STRUCT. MOL. BIOL. 16, 318-324

Gsponer J., Christodoulou J., Cavalli A., Bui J., Richter B., Dobson C. M and Vendruscolo M., (2008) “A coupled equilibrium shift mechanism in calmudulin-mediated signal transduction.” STRUCTURE, 16, 736-746

Signaling protein regulation and evolution

Jothil R., Balaji S., Wuster A., Grochow J.A., Gsponer J., Przytycka T.M., Aravind L. and Babu M. (2009) “Dissecting the dynamics of yeast transcription factors” MOL. SYSTEMS BIOLOGY. 5:294

Gsponer J., Futschnik M., Teichmann S. and Babu M. (2008)“ Tight regulation of intrinsically unstructured proteins: from transcript synthesis to protein degradation” SCIENCE, 322, 1365-1368

Protein misfolding and aggregation

Bui J., Cavalli A. and Gsponer J., (2008) “Identification of aggregation-prone elements using interaction energy matrices.” ANGEW. CHEM. INT. ED., 47, 7267-7269.

Gsponer J., Haberthuer U. and Caflisch A. (2003), “The role of side chain interactions in the early steps of aggregation: Molecular dynamics simulations of prion-like peptides.” , PROC. NATL. ACAD. SCI. USA , 100, 5154-5159.

History

Member for

35 weeks 1 day