Organization of cytoplasm across space and time
Many key biochemical reactions take place in the cytoplasmic environment. However, we still know very little about the organization of the cytoplasm and the role of specialized cytoplasmic compartments such as RNP granules in regulating cellular functions. My research group aims to elucidate molecular principles underlying the spatiotemporal organization of the cytoplasm. We are particularly interested in understanding how the cytoplasm changes upon environmental perturbations and stress (Figure 1). Stressed cells undergo controlled changes on many levels to alter their physiology and metabolism. Many of these changes may directly result from alterations in the structure and organization of the cytoplasm. Understanding these structural changes and how they promote organismal survival is our key aim.
To investigate this question, we are using cell biological, biochemical, biophysical and genetic approaches and diverse model systems, such as yeast, Dictyostelium, and cultured mammalian cells, thus allowing us to cover a wide range of different organismal life styles. Our findings so far indicate that the mechanisms by which macromolecules assemble into compartments are diverse and involve dedicated cellular factors, such as prion-like proteins that promote the formation of liquid compartments, or protein self-assembly pathways that are controlled by changes in global parameters such as the cytosolic pH.
Importantly, the ability to form such compartments seems to come with a cost, as many compartment-forming proteins have a high propensity to misfold and aggregate. Indeed, we could recently show that compartment-forming proteins have very unusual molecular properties and are associated with age-related diseases (Patel et al., 2015). Thus, our long-term aim is to gain insight into the important link between the compartment-forming abilities of proteins and age-related protein misfolding diseases.