High Content Imaging Technology in safety sciences

Organized by:

Center for Alternatives to Animal Testing - Europe (CAAT-Europe), ecopa, ESTIV, HIS, IVTIP, the set foundation and The Transatlantic Think Tank for Toxicology - t4

Date and location:

21st to 23rd October 2013, in Mainz, Germany

Goals of the workshop:

This workshop aims to define the current and future role of High Content Imaging systems in understanding and identification of damage mechanisms and underlying pathways of toxicity. The focus lies on the multidisciplinary input from the fields of modeling, data mining, cell biology and molecular biology to describe new approaches for HCI systems in safety sciences.

Topics to be addressed:

  1. Methodical, technical and biological (reporter, biomarkers) status quo, discussion of gaps and shortcomings to assess cell functions.
  2. Identification of mechanistically defined new and specific endpoints for organ and systemic toxicity which can be addressed with HCI technology
  3. Defining the role of HCI technology in hypothesis validation (e.g. siRNA).
  4. Quality control and interpretation of multiparametric HCI data for predictive toxicology.
  5. Considering the perspectives from the fields of modeling, data mining, cell biology and molecular biology for the definition of progressive HCI approaches in toxicology.

Workshop set-up:

The workshop will bring together a small steering board and maximum of 12 experts from areas of pharmacology, toxicology, systems biology, data analysis for a 2,5-day meeting. Preparation of the workshop by the attendees providing a 2-page discussion paper (each) prior to the meeting.

Outcome objective: An expert report to be published in a peer-reviewed journal.

Background:

The term High Content Imaging (HCI) is used to describe automated microscopy and automated image analysis to provide quantitative data from cellular assays. These multi-parametric data sets can be obtained from large numbers of cells and with high-throughput in an observer-independent standardized way. With the HCI approach different endpoints can be correlated within one cell.

In safety sciences the understanding of adverse outcomes depends on the identification molecular pathways underlying the toxic effects. The identification of these critical pathways of toxicity (POT) and the understanding of the key perturbations leading to adverse effects can be accomplished by using in vitro biochemical- and cell-based assays such as HCI.

This workshop has its focus on the possibilities of the HCI technology for examination of POT underlying damage mechanisms in vitro. Here inter- and intra-cellular signal molecules, organelle involvement, phenotypical changes of the cell, the role of transcription factors, special reporter systems and biomarkers for organ and systemic toxicity will be discussed. By describing the status quo, discussing the gaps and methodical/technical shortcomings and introduction of perspectives from the fields of modeling, data mining, cell biology and molecular biology the summary report is expected to support the further implementation of this important technology. A focus will be on how phenotypic and signaling changes are linked to functional impairment and cell fate: Ho are data interpreted with respect to adversity.

Coordinators:

Marcel Leist and Mardas Daneshian