Welcome to the eilslabs

The eilslabs form a joint research group between the division "Theoretical Bioinformatics" at the German Cancer Research Center (dkfz) and the department Bioinformatics and Functional Genomics at the Institute of Pharmacy and Molecular Biotechnology (IPMB) at Heidelberg University. The group is headed by Prof. Roland Eils.

 


The Signal Transduction Biophysics group has published a paper describing an innovative method to measure spatial and temporal activity of caspases in living cells. The group of Joel Beaudouin has developed reporter proteins, which combine a fluorescent protein and an intracellular location signal, which are connected through a caspase cleavage sequence. Combinations of different fluorescent reporters, localization domains and substrate sequences enabled parallel measurements of different caspase-activities at different cellular compartments within the same cell.

With this new tool it was possible to get new insights into the CD95 signaling cascade. Up to now it was claimed that caspase 8 needs to be fully cleaved by itself and released into the cytosol in order to cleave its substrates Bid and caspase 3. However, Joel and his co-authors could show, that caspase 8 is already fully active and can cleave its substrates from the cell membrane without complete self-cleavage in order to trigger programmed cell death.The developed reporters are a new tool enabling the study and modeling of the initiation as well as the signal transduction via caspases depending on the concentration and spatial distribution of signaling molecules involved in the apoptotic cascade.

Beaudouin et al 2013
Membrane-bound reporters are cleaved more efficiently than soluble cytosolic reporters. The latter are cleaved more efficiently than reporters, which have no access to the cell membrane, e.g. on the surface of the ER. Shown are HeLa-cells overexpressing the CD95 receptor. Scale 10µm (Source: Joel Beaudouin)

Original Publication:

Beaudouin J, Liesche C, Aschenbrenner S, Hörner M and Eils R (2013) Caspase-8 cleaves its substrates from the plasma membrane upon CD95-induced apoptosis. Cell Death and Differentiation advance online publication, 11 January 2013; doi:10.1038/cdd.2012.156