Biological cluster:
dynamic assembly and functional properties of supramolecular complexes in cells

Details of Research Area

In cells, protein complexes are clustered to a higher order structure called “supramolecular complexes”, which governs various cellular functions. In recent years, with advances in cryo-electron microscopy (EM) techniques, many studies have been conducted to elucidate the structures of molecular complexes reconstituted in vitro, but such studies alone often fail to understand how complexes function in cells. This is because in vitro complexes do not reflect with in vivo supramolecular complexes functioning in cells. In vitro complexes sometimes make a condensate. However, such disordered condensates do not reproduce the organized supramolecular complexes formed in cells. In this Research Area, we define “Biological Clusters” as functional “supramolecular complexes” and aim to clarify their formation mechanisms and functional properties, and understand how they generate cellular functions. The Planned Research will focus on supramolecular complexes constituting kinetochores, centromeres, chromosomes, and centrosomes, but the Publicly Offered Research will not be limited to these but will cover a wide range of supramolecular complexes formed in cells. The research will be conducted by analyzing the ultrastructure and molecular dynamics of supramolecular complexes, measuring physical quantities, and developing theory and computational science. We aim to establish a new cellular view of Biological Clusters by clarifying the mechanisms of formation of various Biological Clusters and the relationship between their acquired properties and cellular functions.

Call for Proposals and Expectations for Publicly Offered Research, etc.

Research Group A01 aims to elucidate the molecular basis of various supramolecular complexes, from the structure of their basic units to the regulation of supramolecular complex formation and their cellular functions. The Planned Research will focus on kinetochores, centromeres, chromosomes, and centrosomes, but we welcome research that targets a wide range of important supramolecular complexes, including those involved in transcription, replication, various organelles, and nuclear membrane. Research on supramolecular complexes that function in special environments, such as neurons, aging and stress responses, and diseases, is also eligible.
Research Group A02 focuses on advanced high-precision imaging analysis to solve the structure of supramolecular complexes and elucidate their properties and molecular dynamics. In addition to cryo-ET (electron tomography) and super-resolution imaging, we encourage technologically advanced research for analyzing supramolecular complexes, such as atomic force microscopy, NMR, crosslinked mass spectrometry, deuterium exchange mass spectrometry, development of probes applicable to fluorescence microscopes and new techniques, and methodologies not envisioned in the Planned Research.
In research Group A03, we will measure physical quantities of supramolecular complexes and conduct mathematical analysis parallelly, to elucidate the functional properties of clusters and the elements involved in their formation. In particular, we envision research that attempts to explain complex formation based on simulations that mimic the intracellular environment and research that describes the physical properties of supramolecular complexes. We also welcome research proposals that attempt to demonstrate physical theories that could be applied to cell biology.
Publicly Offered Research proposals are expected to be complementary to the Planned Research and to promote mutually beneficial research through joint research. In the experimental field, research up to 5 million yen per year and exploratory research up to 3 million yen per year will be selected. Theoretical research up to 3 million yen per year is also selected.

Research Group, Upper Limit of Annual Budget and Number of research projects scheduled to be selected