Workpackage

Predictomics' partners are divided on six workpackage. If you want to know the objectives of each group, click on them:

Workpackage 1: Liver cell model developments
Leader:Department of Toxicology. Faculty of Medicine and Pharmacy. Vrije Universiteit Brussel, (Belgium)


Objectives:

  1. To improve phenotype stability in 3D-collagen cultures . Counteracting dedifferentiation of organotypic 3D-cultures of (rat/human) hepatocytes by molecules acting on chromatin structure and/or by key liver-enriched transcription factors.
  2. Generation of stable differentiated human hepatocellular cell lines by transfection with key liver-enriched transcription factors and nuclear factors
  3. Generation of functional human hepatocytes through adult stem cell technology

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Workpackage 2: Kidney cell system developments
Leader:Institute of Physiology. University of Innsbruck. Fritz-Preglstr. Innsbruck, (Austria)


Objectives:

  1. To optimise renal cell culture systems to better reflect the in vivo state and act as more predictive models of nephrotoxicity
  2. To establish static mono-cultures of primary rat and human proximal tubular cells
  3. To develop co-cultures of human glomerular mesangial, epithelial, proximal tubular cell lines and renal interstitial fibroblasts
  4. To adapt static mono- and co-culture systems to systems with continuous medium (toxin) perfusion
  5. Assessment of differences in gene expression between mono and co-cultures at an early and late time point during cultivation. Assessment of changes in gene expression for perfusion culture.

Workpackage 3: Optimisation of tools and analyses
Leader: Department of Pharmacology. Conway Institute of Biomolecular and Biomedical Research. University College Dublin, Belfield, Dublin (Ireland) / Progenika, Derio ,Vizcaya (Spain)


Objectives:

  1. To optimise and technologically improve genomic tools to increase sensitivity.
  2. To improve proteomic analysis . Comparative analysis of 2D-MALDITOF vs protein chips
  3. Development of new cytomic assays

(Up)

Workpackage 4: Identification of mechanistically based cellular parameters. Studies with model toxicants (Hepatotoxicity)
Leader: Unit of Experimental Hepatology. University Hospital La Fe , Valencia. (Spain)


Objectives:

  1. Studies with model toxicants (Hepatotoxicity). Analysis of effects related to the mechanisms of toxicity.
  2. Identification of marker genes related to the mechanisms of toxicity. It is aimed at identifying which of the many genomic/proteomic/ cytomic changes observed in hepatocytes are relevant to the mechanism of toxicity.
  3. Design of a combined strategy for long-term toxicity prediction. The ultimate goal of this project is to propose a combined platform where by assessing specific parameters either at genomic, proteomic or cytomic level, toxicity relevant early changes can be monitored, and sustained warnings can be made concerning the potential hepatotoxicity of a new compound.

(Up)

Workpackage 5: Mechanisms of nephrotoxicity and identification of toxicity markers
Leader:Department of Nephrology. Leiden University Medical Center, Leiden. (The Netherlands)


Objectives:

  1. Identifying mechanisms of nephrotoxicity and mechanistically relevant marker genes by using the cell systems developed and improved under workpackage 2..
  2. By the combined use of genomics , Relevant, deregulated marker genes will be identified using genomics, proteomics and cytomics and genes involved in the development of chronic renal diseases .

Workpackage 6: Database collection. Analysis of model predictivity. Prevalidation. Application of results to drug development, drug surveillance
Leader: Research Toxicology. Bayer A.G. (Busines Group Pharma). Wuppertal, (Germany).


Objectives:

  1. Generation of toxicity data (hepatic and renal) from a set of compounds selected with the final goal to test the consistency and predictivity of the predictomics platform.
  2. Explore issues related to the validation, commercial exploitation of the platform, patent protection of the inventions, and dissemination strategies , for which specific action plans are envisaged.