The Sterneckert group has a strong background in using pluripotent stem cells to model neurodegenerative diseases and identify novel therapeutic strategies. Key research topics have included the role of condensates such as stress granules in motor neurons and ALS. The group developed a model of inflammation in ALS models by using multiple stem cell-derived cell types¹, thereby enabling a screening campaign identifying novel protective compounds. In addition, the group used gene editing to generate one of the first isogenic models of a neurodegenerative disease², and we built on this platform by generating reporter lines for FUS-ALS, which forms condensates in vivo³, enabling the identification of a role for protein-protein interactions in buffering FUS phase behavior⁴. To facilitate the study of condensates in axons as well as functional neuromuscular junctions in higher throughput, the group developed methodologies microfluidic devices⁵. In collaboration with Hyman and Alberti, the group has shown that RNA plays an important role in regulating the phase behavior of ALS-associated RNA-binding proteins, including FUS⁶.

The Ebisuya group has a strong expertise in stem cell and developmental biology, focusing on fundamental questions such as why different animal species exhibit varying biological times. Utilizing stem cell-based models, they have made significant strides in this field. Notably, they have successfully recapitulated the developmental timing mechanism known as the segmentation clock using stem cells from a wide range of mammalian species, including mice, humans, rabbits, cows, marmosets, and even rhinoceroses^1,2,3,4. Through this innovative “stem cell zoo” platform, they demonstrated that cells from each species retain their distinct developmental tempo and biochemical kinetics in vitro. Currently, the team is investigating species-specific distributions of biomolecular condensates and their role in shaping these unique developmental tempos.

The Hyman group has made significant contributions to molecular and cell biology, particularly in understanding the mechanisms of cell division and cell compartmentalization. Perhaps the two most notable achievements include utilizing RNA interference to map various cytoplasmic processes¹ and discovering that compartments in cells can form via phase separation². Their expansive body of work has also illuminated fundamental interworking of protein complexes and cellular structures like the mitotic spindle, centrioles, and P granules^3,4. Currently, their research is aimed at exploring how phase separation of intrinsically disordered proteins may drive neurodegenerative diseases including ALS.

The Brugués group has a strong background in biophysics, combining both theory and experiments. From the experimental side the Brugués lab uses cytoplasmic extracts, in vivo measurements and in vitro reconstitution. Key research topics have included co-condensation of DNA and protein interactions^1,2, methods to quantitatively measure protein concentration in condensates³, reconstitution of chromatin processes in single DNA strands⁴, and self-organization and mechanics of the mitotic spindle as an active liquid droplet^5-8. In recent years, the group has developed a theoretical framework for polymers in mixed solvents which explaining unusual phase transition scenarios. In collaboration with the Alberti and Jahnel groups, we have demonstrated that capillary-like forces arising from DNA-protein interactions play a key role in DNA damage².

The Alberti group studies how cells adapt to environmental stresses by assembling biomolecular condensates. The group applies biophysical, biochemical, genetic, and cell biological methods to investigate the molecular mechanisms of assembly and the functions of stress inducible condensates. Among others, the Alberti group has shown that condensate assembly regulates protein synthesis^1-3, stress responses^1,2,4,5,6 and the DNA damage response^7,8. Most importantly, the Alberti group discovered together with the Hyman group that condensate-forming proteins can assemble into aberrant condensates that cause aging-associated diseases^7,6,9,10. In collaboration with the Schlierf group, the Alberti group recently established a model for the assembly of RNP granules and their function in regulating RNA availability and translation.