Linking Metabolic and Cell Cycle Regulation

One of the most fundamental challenges in modern biology is to understand how cells process and integrate information into coordinated physiological responses. Importantly, cells must coordinate the regulation of growth and division, with the catabolic and anabolic pathways that provide the energy and raw materials necessary for all cellular activities. Determining the mechanisms responsible for this coordination of metabolism with the cell division is fundamental for understanding human physiology and disease states such as cancer, the ecology and evolution of single cell organisms in their environments, as well as the constraints governing metabolic engineering of these organisms.

The Ewald lab combines live cell imaging, biochemistry and ‘omics’ to understand how metabolism and growth are coordinated with the cell division cycle in the model organism budding yeast.

Current research questions in the lab:

How does nutrient supply control cell cycle progression?
It is well known that cells arrest in the G1 phase of the cell cycle if nutrient supply is not sufficient. But what about cells that are not in G1? Using our microfluidic cultivation systems, we grow yeast cells under the microscope and change their nutrient supply. We then watch how cells in different cell cycle phases respond to this nutrient switch. See our recent paper: When Yeast Cells Change their Mind: Cell Cycle “Start” is Reversible under Starvation

How does cell cycle progression regulate metabolism?
When cells progress through the cell cycle they go through different macromolecular processes such as DNA synthesis and chromosome segregation. We want to understand how these processes “tell” metabolic pathways to supply the right amount of building blocks and energy. Our previous work showed among other things that the cyclin-dependent kinase CDK directly regulates metabolic enzymes and signaling pathways (Ewald et al 2016, Zhang et al 2019).
Our current focus in this area is understanding how mitochondria are regulated during the cell cycle. This project is part of the MOMbrane graduate training group.

How do signaling pathways talk to each other?
The cyclin dependent kinase is the most important driver of the cell cycle. The protein kinase A pathway is a nutrient sensing pathway that controls metabolic fluxes and growth rate. We are investigating how these two pathways interface. For example, we have studied how these kinases act on a common substrate, the trehalase Nth1 (Dengler et al 2021). We are now investigating how the signaling proteins upstream of PKA receive signals from the cell cycle.