Factors that determine RIPK1-dependent necroptosis

01 January 2018 → Ongoing
Research Foundation - Flanders (FWO)
Research disciplines
No data available
Project description

When TNF is binding to TNF receptor 1 (TNFR1), the cellular outcomes can be fundamentally

different: survival and pro-inflammatory signaling versus cell death signaling to apoptosis or by

necroptosis. The former outcomes are initiated by receptor-associated complex I formation, while

the latter outcomes are a consequence of a cytosolic complex II. In this project we want to visualize

the dynamics of this complexes, especially complex II by using cellular biosensor constructs. These

will be used to identify and validate the biochemical and cellular processes (Ca++, ROS, metabolism,

pHi) that are crucial in the propagation of necroptosis. If we can successfully visualize these cellular

outcomes, we also want to develop transgenic models in which we can score the dynamics of these

processes in vivo or ex vivo. Fundamental insight in the cell biology of necroptosis regulation has

important biomedical implications on the long term, to examine which pathophysiological

conditions are associated with necroptosis and to develop strategies to modulate cell death

outcomes by cellular and metabolic conditions rather than targeting the process itself.