ANDREAS KOHLER

As we age, the ability of our cells to maintain their internal machinery declines, contributing to the development of many age‑related diseases. One of the most affected components are the mitochondria, which are essential for supporting cellular metabolism. They use nutrients from our diet and oxygen from the air we breathe to carry out cellular respiration, a biochemical process that provides cells with most of the energy needed for their normal functions.

To perform this work, mitochondria rely on a small but crucial set of proteins that are made directly inside the organelle. These proteins are indispensable for mitochondrial function, yet they are also exceptionally challenging to produce and maintain. Errors in their production accumulate as we age, and these defects are strongly linked to age‑associated disorders, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. To prevent such harmful effects, mitochondria depend on quality‑control systems that monitor and maintain the integrity of newly produced proteins. Despite their importance, these mechanisms remain poorly understood. We still lack a clear picture of their molecular components, how they function, and how they change during ageing.

In this project, Andreas Koehler and his team will use the baker’s yeast Saccharomyces cerevisiae as a model organism and perform large‑scale genetic screens to identify new components and regulators of the systems that ensure the quality of proteins synthesised inside mitochondria. He aims to define their molecular roles, determine how they interact with the mitochondrial protein‑synthesis machinery, and understand how their activity changes as cells age. Additionally, the team aims to develop strategies to modulate these pathways in order to support cellular fitness during ageing.

This research addresses a major global health challenge: the increasing impact of age‑related diseases on individuals, healthcare systems, and societies. By uncovering the fundamental principles that protect mitochondrial proteins throughout life, this project provides a foundation for future strategies aimed at maintaining cellular resilience and slowing age‑associated decline.