We aim to determine the causes and consequences of macromolecular crowding. Cells are dense with proteins, DNA, and RNA; these biomacromolecules continuously interact in a Brownian storm through steric and associative or repulsive interactions. On pure steric grounds, one would expect crowding to reduce the volume of a given protein or protein assembly (in most cases). However, the cell is obviously not a box of marbles: So how are all these biomacromolecules organized, and how does this affect the macromolecular crowding effects? Which proteins are involved, and which macromolecules could change shape and function? Is macromolecular crowding essential for living cells? Should we take them into account when considering disease? How does it affect disease-associated protein (mis)folding, aggregation, and the protein homeostasis network?

This is a sample of the questions we address in our research. As tools to obtain more insights, we develop novel protein-based sensors for macromolecular crowding, protein self-association, ionic strength, and others, and apply these inside living cells. In addition, we recreate our findings from living cells inside artificial cells as a much-simplified model where we can control relevant aspects of the living cells. In this manner, we aim to improve our understanding of the molecular (self-)organization.

For more details, please visit our group website: www.boersmalab.com.