Objectives

  

AgedBrainSYSBIO aims to address the basis of brain ageing by studying the pathways involved in this process and by identifying the interactions through which the ageing phenotype develops in normal and in disease conditions. The project aims at identifying and validating new molecular targets and biomarkers associated with late-onset Alzheimer's Disease. As early steps of neurodegenerative disorders are expected to impact synapse function the project will focus in particular on pre- or post- synaptic protein networks. 

  

 

AgedBrainSYSBIO will use literature data, Genome Wide Association Studies (GWAS) for Late-Onset Alzheimer Diseases (LOAD) and Protein-Protein Interactions (PPI) studies to accurately detect protein interactions and their location. From these data, novel pathways and their evolutionary properties will be modeled and experimentally tested in order to identify druggable targets. The identified pathways will be tested using animal model systems (mouse and drosophila) and patient-derived neurons. AgedBrainSYSBIO will be using human pluripotent stem cell lines and in particular human induced pluripotent stem cells (hiPSC) based on their capacity to self-renew and differentiate into virtually all cell types of the human body and animal models. hiPSC will be generated by reprogramming of somatic skin fibroblasts from healthy donors and patients with late and early-onset AD. From these approaches, AgedBrainSYSBIO expects new validated targets to emerge providing new diagnostic tools and new drug discovery programs that will directly benefit to ageing populations.

 

 

The major objectives of the project are:

  • Identify and model pathways in systems biology - We will perform large-scale data integration and analysis of AgedBrainSYSBIO data sets and publicly available background information on pathways, transcription factors and their binding sites, protein interactions, etc.  Computational models leading to new understanding of the aetiology of LOAD and related neurodegenerative diseases will then be developed.
  • Understand human and/or Primate evolutionary accelerated properties of pathways  - Important species-specific differences in genome and protein composition are probably major causes of the limitations of the mouse models. We will perform evolutionary analyses that should be instrumental in directing experiments in model organisms and correlating their results to the human phenotype.
  • Elucidate protein-protein interactions - Novel approaches will be used to accurately detect protein interactions and their location in the organs, in the cell types and in a sub-region of a given neuron
  • Manipulate pathways relevant to LOAD - We will employ comparative transcriptomics to identify de-regulated signalling pathways in patient-iPSC derived neurons.
  • Drug discovery - Advance validation of selected interactions as drug target will be conducted in vivo

Last update on 2016-07-22

AgedBrainSYSBIO has received funding from the European Union’s Seventh Framework Programme for research,
technological development and demonstration under grant agreement No 305299
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