Mapping out crosstalk between the protein quality control machineries of mitochondria, cytoplasm and nucleus to decipher aging and dying as a process

Aging is a dominant risk factor for many widespread diseases and their collective impact on human wellbeing and health care systems provides the impetus for deciphering the underlying cause and origin of the aging process.

Emerging data suggests that specific network and organelle intersections are more sensitive to change and decline and therefore drive the aging process by causing a sequential, domino-like, decay of the connected subsystems.

This interdependency appears especially important for protein quality control systems, which are the focus of this project and my previous VR-funded projects.

I believe that mapping out the genetic crosstalk and interaction network between the mitochondrial and the nuclear genomes, in connection with data on how inter-organelle communication changes during aging will provide both insights into hitherto unexplored areas of organelle interconnectivity and how organelles change during the aging process.

While an important phenotypic readout, lifespan is an endpoint assay with limitations in providing mechanistic understanding of the aging process.

In order to gain fundamentally new, and dynamic, insights into this process, we will therefore development an automated imaging pipeline, using mother cell traps, for real-time detection of changes in subcellular morphology that cells undergo through time as they are dying, known as the terminal phenotype.