Molecular dynamics of size sensing at the single cell level.

Cells have strict control over their size to ensure proper cell physiology.

They also have ways to correct for deviations, referred to as cell-size homeostasis, leading to a very narrow distribution in cell size at division.

Although some of the genes involved in this process have been identified, the underlying molecular mechanism has remained elusive.

One possibility is that the cell can “sense” its size through a protein whose concentrations are related to cell-size ‒ known as the sizer model.

However, this would not completely explain the fact that diploid cells are approximately twice the size of haploids, suggesting that ploidy also plays a role ‒ something that has not garnered a lot of attention in the field.

Live-cell fluorescence microscopy is well-suited to address these issues because we can directly visualize the dynamics and localization patterns of sizers, along with cell-size, and quantify these characteristics.

I propose to develop a live single-cell fluorescence microscopy approach using a microfluidics device that allows mother cell lineages to be tracked across multiple generations, for use with haploid and diploid strains of the unicellular eukaryotic organism, Schizosaccharomyces pombe.

This will allow me to measure protein levels of sizer candidates and their localization, along with cell length, across single lineages.

This information could reveal long-term dynamics and correlations between sizer candidates and cell-size, and provide insight into the molecular mechanisms governing cell-size homeostasis and the role that ploidy plays in governing cell-size control within eukaryotes.