Cells are the smallest individual units in organs that altogether define organ function. Organs are composed of many different cell types. Chemicals and their metabolites may affect the function of different cells in different organs, with each affected cells resulting in different pathological consequences. This course will discuss the routes by which chemicals affect cells and how cells respond to this situation.
Aim of the course
To provide understanding of cells as the primary target of organ toxicity, the molecular mechanisms involved in cellular toxicity, and the technological approaches available to identify and understand cytotoxicity.
Content of the course
The course is composed of lectures, demonstrations, literature discussions and a theoretical assignment. In a series of lectures the concepts of and the biochemical and molecular aspects of cell toxicity are illustrated using liver and kidney as a model target organs. Special emphasis is on the mechanisms of cell killing by necrosis and apoptosis, typical endpoints of tissue injury. Furthermore, signalling pathways that are central in the control of the cytotoxic outcome will be discussed. The use of state-of-the-art high-content live cell imaging technologies and RNAi-based approaches to understand mechanisms and to screen for adverse cellular responses will be demonstrated. At the end of the week participants will discuss hypothetical candidate in vitro models for different organs.
Outcomes (competences, skills)
On successful completion of the module, participants should:
• have a basic understanding on the pros on cons of in vitro cell systems in toxicology research
• understand the biochemical programs that underlie necrosis and apoptosis
• pinpoint the most important cellular stress responses that occur during chemical exposure and translate injury into death or repair programs
• understand the use and application of state-of-the-art technology for in vitro cell toxicology research
• be able to critically apply the above information in designing and/or critically evaluating in vitro models for predicting toxicity.
Prof.dr. B. van de Water
Dr. E. Danen
Dr. M. de Graauw
Dr. L. Price
Dr. J. Meerman
At the end of the week (Friday afternoon), the participants will give an oral presentation and hand in a written report on the theoretical assignments, which will subsequently be discussed.
Coordinator(s): Prof.dr. B. van de Water
Duration: 1 week
ECTS credits: 1.5
Number of participants: 15-20
Period: for exact dates, please consult the current programme schedule
Fee: see tuition fees (includes reduced fees for PhD students)
Location: LACDR, Div. Toxicology, Gorlaeus Laboratories, Leiden University, Leiden