Research Groups

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. 

<b>Figure 1:</b> Research focus of the Alberti lab. The figure shows an idealized cell, which transitions into a different state upon stress. This transition is associated with changes in the organization of the cytoplasm and the formation of large macromolecular assemblies. In normal cells, the macromolecules are not interacting with each other (unassembled). However, upon stress, these macromolecules interact and form assemblies with specific material properties (liquid or solid condensed matter state). Thus, the overall process has hallmarks of a phase transition. Stress-induced assemblies can either function as storage depots or as compartments for concentrated biochemical reactions.

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.