Protein interactions at multiple scales

General info

Date from - to

01 Jan 2005 - 01 Dec 2010

Project leader(s)

Heringa, Jaap Prof. dr.

Participant(s)

Huynen, Martijn A. Prof. dr.

Ham, van Roeland Dr.

Bos, Johannes L.

Siezen, Roland J. Prof. dr.

Snel, Berend Dr.

Abstract

Genotype defines phenotype by a network of molecular interactions: key to all cellular processes. This project develops and tests bioinformatics tools that analyse interactions based on a variety of (genomics) data. The scale at which the interactions take place, vary, as do the interacting substrates. In spite of these variations, underlying mechanisms are quite similar. The complementary expertise of the various groups provides an excellent basis for collaboration.

This project will study protein complexes to illuminate the association/dissociation dynamics of protein complexes in solution, and even the ferocious problem of complex and cluster formation in different cellular environments. Pair-wise protein interactions will be studied by machine learning techniques. Various types of ~omics data will be used, but also sequence and structure-information of the interacting partners. Protein-DNA interactions will be predicted for the transcription regulatory networks in bacteria by 'phylogenetic footprinting'. This will enable detection of regulatory elements in whole genomes. The Golgi apparatus functions as a central delivery system in the cell. Are there signals present in protein sequences that interact with this apparatus? Finally, two extremely complex signal-transduction pathways, associated with oncogenesis, will be analyzed. This will in part be driven by previous results, and will direct new wet-lab experimentation.

Link to the end report of this project

Publications

• Challenges in plant cellular pathway reconstruction based on gene expression profiling
• Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance
• Proteomic profiling of Plasmodium sporozoite maturation identifies new proteins essential for parasite development and infectivity
• Clustering of codons with rare cognate tRNAs in human genes suggests an extra level of expression regulation
• Protein complex evolution does not involve extensive network rewiring
• The Cladosporium fulvum virulence protein Avr2 inhibits host proteases required for basal defense
• Sequence comparison by sequence harmony identifies subtype-specific functional sites
• Sequence harmony: detecting functional specificity from alignments
• Exploration of the omics evidence landscape: adding qualitative labels to predicted protein-protein interactions
• Disease induction by human microbial pathogens in plant-model systems: potential, problems and prospects
• Phylogeny of the CDC25 homology domain reveals rapid differentiation of Ras pathways between early animals and fungi
• In Silico Identification of T-boxes: to Study Their Propagation and to Improve the Functional Annotation of Transport Systems
• Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo
• The meaning of alignment: lessons from structural diversity
• Predicting and understanding transcription factor interactions based on sequence level determinants of combinatorial control
• Predicting sub-Golgi localization of type II membrane proteins
• Assessment of phylogenomic and orthology approaches for phylogenetic inference
• A Feature Selection Algorithm for Detecting Subtype Specific Sites for SMAD Receptor Binding
• Phenome connections
• Conservation of divergent transcription in fungi
• Practical and theoretical advances in predicting the function of a protein by its phylogenetic distribution
• Asymmetric relationships between proteins shape genome evolution
• Comparative phosphoproteomics reveals evolutionary and functional conservation of phosphorylation across eukaryotes
• Orthology prediction at scalable resolution by phylogenetic tree analysis
• Conserved co-expression for candidate disease gene prioritization
• Evolution of closely linked gene pairs in vertebrate genomes