One molecule at a time: revealing cell-to-cell heterogeneity upon adaptation to metabolic stress

My goal is to quantify the effect of cellular heterogeneity on metabolic stress-induced protein aggregation.

Based on my previous data, aggregation is a general stress response mechanism where molecular subpopulations play a crucial role.

To reveal those, I will build a super-resolution single-molecule fluorescence microscope to follow protein aggregation directly in living cells and determine how it is regulated via DNA packaging (Aim 1).

I will use FRET-based sensors to correlate protein aggregation with intracellular concentration of two important metabolites, ATP and trehalose, in yeast (Aim 2) and liver cells (Aim 3).By revealing cellular variability, I will uncover strategies that cells undertake to adapt to metabolic stress.

In the future, this can be applied to whole organs and multicellular organisms for understanding of causes and cellular responses to metabolic diseases.

This will open up new thought towards development of next generation therapeutical approaches, such as personalised medicine.

Project implications can be used beyond the scope of this proposal: in studies of cell reaction to infections or development of multi-stress resistant organisms in research of origins of life.In this 4-year project, I will combine the experimental work with supervising a PhD student.

The work will be performed at the Department of Physics, University of Gothenburg, which provides a well-established environment bridging biophysics with fundamental biological questions.