Visualizing Cell Death Inducing Protein Complexes

 

 

Cell death is an essential part of normal developmental processes while inappropriate cell death can lead to disease and is the cause of a range of drug induced toxicities. Recent research has established the existence of distinct cell death processes that occur through the activation of genetically encoded molecular pathways. These regulated cell deaths and are exemplified by apoptosis, necroptosis, pyroptosis and ferroptosis. It has also become clear that these different death processes, are often interlinked, producing complex regulation of cell survival that is poorly understood. Understanding these cell death processes and how they are regulated during development and in disease may lead to new therapeutic approaches to treat disease as well as ways to reduce drug-induced toxicity.

Apoptosis, necroptosis, pyroptosis and some other forms of regulated necrosis are induced by the formation of protein complexes. We now wish to develop the next generation of experimental tools that will allow us to visualise the formation of death inducing protein complexes in both cultured cells and in vivo at a cellular level.

Our aim is to develop a panel of bioluminescence and fluorescent tools that will allow detection of cell death processes in live cells and tissues and to use these tools to study cell death in normal and disease processes and to screen for drugs that modulate their activity.

Our consortium includes cell death experts, bioluminescence experts, zebrafish experts, structural biologists, developmental biologists, and molecular and cell biologists from industry and academia who are actively involved in drug discovery and development. Researcher mobility within the network will provide access to skills, equipment and experience that will both drive the development of valuable experimental tools and enhance the career prospects of the researchers.