Project number 26

Controlling Membrane Permeation in Animal and Plant Programmed Cell Death

Different forms of cell suicide by genetically encoded programs (programmed cell death, PCD) represent fundamental cellular processes that are crucial for the development and health of multicellular organisms. While apoptosis is the best-understood animal PCD type, in both vertebrate animals and plants alternative non-apoptotic PCD forms have evolved. Vertebrate necrotic cell death by necroptosis and pyroptosis for instance has important roles in immunity and leads to inflammatory responses, while plant caspase-independent PCD types are involved in plant development and immunity. A central "point of no return" in both animal necrosis as well as plant PCD is controlled membrane permeation causing the release of cellular contents past membrane barriers. Recent results implicate the mixed lineage kinase domain-like protein MLKL and the gasdermin GSDMD in membrane permeation in necroptosis and pyroptosis, respectively. In contrast, still little is known about cell permeation events in dying plant cells.
In this project, the PhD candidate will investigate the biochemical, genetic, and structural aspects of membrane permeation in necrotic animal cell death and developmental plant PCD in a comparative fashion. Candidate adaptor and execution proteins will be identified by bioinformatics and their effect will be examined in animal and plant cells. The anticipated results will enable us to directly relate the functions of non-apoptotic cell death executers in animals and plants. Combining the complementary advantages of animal and plant model systems will be decisive to advance our knowledge on PCD execution and might provide new leads in the search for novel modes of action in both medical drugs as well as agro-chemicals.

programmed cell death, necrotic cell death, animals, plants, membrane permeation

Moritz Nowack, VIB Dept. of Plant Systems Biology, UGent, Gent
Peter Vandenabeele, VIB Inflammation Research Center, UGent, Gent