Apoptosis Research Group

As apoptosis is genetically regulated, many efforts have been made to isolate the components of apoptosis signalling pathways. The Apoptosis Research Group's own approach was motivated by a conspicuous correlation: most of the genes involved in apoptosis exert their activity upon over-expression, a capacity that is even conserved across species boundaries. It might be explained by the observation that apoptosis is mediated by specific protein-protein interactions, which are induced when one of the partners is over-expressed.

To isolate such dominant, apoptosis-inducing genes, the team has developed a genetic high-throughput screen. This is based on novel read-outs for detecting apoptosis in a 96-well format and a novel method to isolate plasmid DNA in a miniprep format with a purity sufficient for transfections. Moreover, they have constructed transfection and DNA isolation-robots for this screen.

Since testing single gene activities in populations of transfected cells, they obtain favourable signal-to-noise ratios and a high sensitivity in their functional read-out. With this screen, which was named RISCI (robotic single cDNA investigation), they have created a unique research tool that permits to detect genes that have not been implicated in apoptosis before.

Using additional information from extensive literature scans and careful sequence analysis the group has chosen several genes for further studies. They are now investigating a variety of genes and signalling cascades, such as components of the mitochondrial "permeability transition pore" and of the respiratory chain.

At the endoplasmic reticulum they are concentrating on the Bap31 complex, which has recently become a focus of interest in the apoptosis field. Also, the metastasis suppressor KAI1 at the plasma membrane is an important project in the group.

While RISCI still leads to single genes that can induce apoptosis, the groups long-term goal is to establish a signal transduction network of interacting apoptosis sensors that are defined by the genes from the screen. Eventually, the Apoptosis research group would like to learn how they interact and lead to apoptosis induction in a physiological or pathological setting.