1: Toward nerve regeneration and recovery of
central nervous system function
The higher-order structures of the nervous system are exquisitely and beautifully formed. How can a complex neural circuit be created? I have continued my research from this question. I have seen the formation of tissues other than nerves from the mechanism of cell adhesion and analysis of adhesion molecules, but I would like to grasp the construction of the most complicated nervous system and a part of the higher neural functions that are established there. I will. I am trying to analyze cells based on cell organisms, considering their functions by looking at their shapes and structures.
1-1): Recovery of neural function by improving the extracellular environment
Based on the cell biological analysis of neurogenesis and nervous system so far, we started a project of neurogenesis and nerve regeneration using a knockout mouse of sugar chain synthase, targeting sugar chains that are also partners of adhesion molecules.
We found that the function of sugar chain chondroitin sulfate during regeneration in central nervous system / spinal cord injury and its expression control lead to dramatic recovery after central nervous system regeneration and spinal cord injury (Nature Comm. 2013). At the same time, it has been shown that nerve cell adhesion molecules are important for nerve cell migration and cell polarity determination by recognizing the sugar chain structure of chondroitin sulfate. (Nature Neurosci.2013, Neuron 2014)
Based on this result, our laboratory is currently using the mating experiments and genome editing techniques of sugar chain-related knockout mice such as chondroitin sulfate and neuroadhesion molecule knockout mice to further investigate the detailed mechanism of neurodevelopment. We are proceeding with the analysis. In addition, from the perspective of therapeutic application, we are conducting research on various drug screenings related to sugar chain expression and sugar chain modification, basic research on them, and application development to treatment using biomaterials. (AMED drug discovery support project, AMED CiCLE project, etc.)
1-2): Functional recovery by artificial connection of nerve synapses
From the above-mentioned function of chondroitin sulfate sugar chain from the viewpoint of controlling the field of regeneration in central nervous system / spinal cord injury, the artificial chimeric protein CPTX that binds synapses, which is the basic structure of neural circuits, is applied to the central nervous system.・ It was found to be highly effective in functional recovery after spinal cord injury (Science. 2020) <with Professor Keio University, Medical and Yuzuzaki, German Center for Neurodegenerative Diseases, Oxford University, UK and MRC Institute for Molecular Biology International joint research>.
Based on this result, our laboratory is currently conducting research toward the application development of this CPTX and recovery of various neural functions.
(Grants-in-Aid for Scientific Research, New Academic Area Research, etc.)
<Professor Takeuchi Main Project>
<Professor Takeuchi Assistant Professor Sasakura Main Project>
2: Further analysis using molecular cell biology
We are advancing the above gene control and in vivo protein transfer systems by making full use of cell immortalization technology and gene transfer technology.
In particular, as a gene-introduced cell for postoperative application of brain tumors and treatment of spinal cord injury using the constructed life-extending cells by introducing the TART gene into human primary cultured cells (by functioning to maintain telomeres). We are exploring usage etc.
We are also developing applied developments such as chromosome / gene modification technology, technology development, and introduction technology for this purpose.
(Joint research with more companies, such as Grant-in-Aid for Scientific Research)
<Associate Professor Ikeno Main Project>
3: Application to diseases in various organs by controlling extracellular matrix
Using our many types of genetically modified animals, we are conducting research on the function of chondroitin sulfate and its control method in vivo. In particular, we have found that chondroitin sulfate is important for skin formation and facial bone formation (Scientific Res. 2018), and that it is important for the proliferation of neural stem cells involved in memory learning (J. Neurosci. 2018). I will.
How to prepare these extracellular matrix environments in the living body and how to link them to medical treatment, coenzymes (J.Cell Sci.2015 Sasakura et al.) That control these molecules related to longevity, and the amount of chondroitin sulfate We are also researching the use of controllable biological components and functional molecules.
In the analysis of the nervous system, we are introducing new functional analysis methods and analysis systems using AI in order to analyze not only regenerative treatment applications but also how to properly capture pain response and motor function recovery (AMED contract research). , And scientific research funding, new academic area research, etc.).
4: Analysis of recovery after nerve injury using AI and advanced technology
We are advancing the analysis using AI for the recovery of physiological functions for various diseases centering on nerve damage, researching using advanced measurement, and developing technology to accurately detect pain. We are actively developing it as an essential technology for future research development.
(Grants-in-Aid for Scientific Research, New Academic Area Research, Private Joint Research, etc.)