Kurt Schmoller: Cell and Organelle Size Control

The Schmoller lab joined the IFE in August 2017 and is always looking for highly motivated master & PhD students. If you are interested, please send your application to Kurt Schmoller (

From whole animals to subcellular structures, size is a key property that is fundamentally linked to function. Accordingly, the size of cells is tightly controlled and spans many orders of magnitude, depending on species, environmental context and – in multicellular organisms – cell di­fferentiation. For example, the volume of human cells ranges from the 30 μm3 sperm cell to the 100000 times larger oocyte. In addition to controlling size itself, cells must coordinate their size with the size of organelles and intracellular processes. Yet, our understanding of the underlying regulatory mechanisms is surprisingly poor. This can in part be attributed to the fact that size control is a highly stochastic process that is hard to study with traditional bulk methods.

To overcome this challenge, we combine molecular cell biology approaches and microfluidics-based single-cell imaging with concepts of physical sciences and mathematical modelling. Using the unicellular model organism budding yeast, we seek address the following questions:

How do cells coordinate growth and division to control their size?

Recently, we have shown that the major budding yeast size control mechanism is based on the dilution of the inhibitor Whi5 by cell growth, as well as the di­fferential size dependence of protein synthesis. While most proteins, including the activator Cln3, are produced in proportion to cell size, the Whi5 synthesis rate is largely size independent. The Whi5-dilution mechanism opens the door towards a quantitative understanding of cell size homeostasis in budding yeast, as well as its modulation by environmental conditions.

Budding yeast size control is based on the differential size-dependence of the activator Cln3 and the inhibitor Whi5. This demonstrates that while cell size is controlled by the concentration of regulatory proteins, cell size itself regulates protein homeostasis. Source: Kurt Schmoller

Budding yeast size control is based on the differential size-dependence of the activator Cln3 and the inhibitor Whi5. This demonstrates that while cell size is controlled by the concentration of regulatory proteins, cell size itself regulates protein homeostasis. Source: Kurt Schmoller

How does cell size a­ffect fundamental biosynthetic processes?

For a large fraction of the genome, biosynthetic output increases in proportion to cell size. Yet, as highlighted by the special size dependence of Whi5, protein concentrations can be di­fferentially regulated with size. We aim to reveal the role of cell size as a global regulator of protein homeostasis and to unravel the underlying molecular mechanisms.

What are the molecular mechanisms that coordinate cell size with organelle homeostasis and subcellular structure formation?

The size and number of many organelles is tightly linked to cell size and often scales in direct proportion. Live cell imaging combined with manipulations of cell size provide a powerful tool to identify the principles by which cell size governs organelle formation and maintenance.

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