Protein Interaction Networks and Disease: Highlights of the 3rd Challenges in Computational Biology Meeting

Cellular functions are managed by a complex network of protein interactions, the malfunction of which may derive in disease phenotypes. In spite of the incompleteness and noise present in our current protein interaction maps, computational biologists are making strenuous efforts to extract knowledge from these intricate networks and, through their integration with other types of biological data, expedite the development of novel and more effective treatments against human disorders. The 3rd Challenges in Computational Biology meeting revolved around the Protein Interaction Networks and Disease subject, bringing expert network biologists to the city of Mainz, Germany to debate the current st…

Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery

Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expr…

Editorial: Protein Interaction Networks in Health and Disease

The identification and annotation of protein-protein interactions (PPIs) is of great importance in systems biology. Big data produced from experimental or computational approaches allow not only the construction of large protein interaction maps but also expand our knowledge on how proteins build up molecular complexes to perform sophisticated tasks inside a cell. However, if we want to accurately understand the functionality of these complexes, we need to go beyond the simple identification of PPIs. We need to know when and where an interaction happens in the cell and also understand the flow of information through a protein interaction network. Another perspective of the research on PPI n…

Protein Interaction Networks in Health and Disease

Dynamics of a Protein Interaction Network Associated to the Aggregation of polyQ-Expanded Ataxin-1

Background: Several experimental models of polyglutamine (polyQ) diseases have been previously developed that are useful for studying disease progression in the primarily affected central nervous system. However, there is a missing link between cellular and animal models that would indicate the molecular defects occurring in neurons and are responsible for the disease phenotype in vivo. Methods: Here, we used a computational approach to identify dysregulated pathways shared by an in vitro and an in vivo model of ATXN1(Q82) protein aggregation, the mutant protein that causes the neurodegenerative polyQ disease spinocerebellar ataxia type-1 (SCA1). Results: A set of common dysregulated pathwa…