Tomohisa Hosokawa

Lecturer, Graduate School of Science, Nagoya University *Profile is at the time of the award.

2023Inamori Research GrantsBiology & Life sciences

Research topics
Suppression of Parkinson’s disease via liquid-liquid phase separation
Keyword
Summary
Protein called α-synuclein form cytotoxic aggregates in the neurons of Parkinson's disease patients. Thus, suppressing or destroying this aggregation is important to inhibit the progression of the disease. Recently, it has been revealed that α-Synuclein forms "condensates," which are reversible liquid-phase structures in cells through a physical phenomenon called liquid-liquid phase separation, and undergoes a phase transition to aggregates. Therefore, in this study, we will identify the factors that achieve discrete condensates, inhibit phase transitions, and inhibit the propagation of phase transitions, with the aim of discovering strategies to inhibit the progression of Parkinson's disease.

Comment

I am fascinated by the mystery of the phenomenon of phase separation, in which proteins assemble autonomously and acquire ordered structure and function, and I am constantly amazed by this phenomenon in my research.

Outline of Research Achievments

Aiming to manipulate liquid-liquid phase separation at synapses, we worked on establishing a computational model, comprehensively identifying co-condensation factors, and developing tools for the optogenetic manipulation of synaptic proteins. In establishing the computational model, we found that changes in surface tension generated by structural flexibility, in addition to binding valency, are crucial for phase separation and the formation of sub-phases within the condensate. In the comprehensive identification of co-condensation factors, we were able to identify multiple presynaptic terminal factors likely to co-condense with phase separation drivers. With the optogenetic tools, we induced synapse shrinkage through attempts to reduce binding valency using photocleavable proteins. This suggests the possibility of suppressing phase separation within the microenvironment of the synapse.


Vikas Pandey, Tomohisa Hosokawa et al. (2025) Multiphasic protein condensation governed by shape and valency Cell Reports 44 (4) doi:10.1016/j.celrep.2025.115504


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Biology & Life sciences