Platform technology (assay systems and analysis methods)
Clinically applicable methods to measure clearance of abnormal proteins from brain
In many of neurodegenerative disorders including Alzheimer's disease, accumulation of abnormal proteins in the brain is the main pathological change. As a cause of such accumulation, dysfunction of glymphatic system, a brain drainage system, that removes such abnormal proteins from the brain, has attracted attention in recent. Therefore, accurately quantitatively measuring the feature of this glymphatic system is extremely important. Although some measurement methods using MRI have been reported so far, a more convenient and versatile measurement method is desirable. In this recruitment, we would like to adopt basic researches that fit for it. However, those that remain just at animal experiment level due to some limitations such as being invasive should be excluded. We do want those that are applicable to clinical settings through translational researches.
Research on cellular senescence in neurodegenerative and neurodevelopmental diseases
Calling for research that can contribute to the understanding of involvement of cellular senescence and to future drug discovery targeting cellular senescence in central nervous system diseases.
Areas of interest:
Novel drug target and biomarker identification targeting liquid-liquid phase separation for neuro-degenerative disease
Liquid-liquid phase separation (LLPS) has recently attracted considerable attention involving RNA stress granule and autophagy. It is expected that new therapeutic drugs and biomarkers could be provided by targeting LLPS. We would seek broad research ideas regarding LLPS, such as drug target, innovative drug screen assay, and identification of patient stratification biomarker focusing on LLPS mechanism.
System development for isolation of tissue-specific extracellular vesicles with superior selectivity, yield and throughput to conventional immunoprecipitation
Recently, extracellular vesicles (EVs), including exosomes, are gaining momentum as biomarkers. Especially, tissue-specific EVs may enable detection of (patho-) physiological changes in the target tissue using only peripheral blood, thus making conventional, invasive biopsies obsolete. This is commonly referred to as “liquid biopsies”. The most common method for enrichment of tissue-specific EVs is immunoprecipitation, where antibodies against EV surface antigens are used. However, these methods have several drawbacks, including limited number of available antibodies, low yield, non-specific binding, low throughput and lack of quantitavity. We want to recruit groundbreaking ideas to overcome these methodological weak points. The submitted ideas should realize at least either or all of the followings: (1) a system adopting other targeting element than antibodies such as aptamer, (2) utilization of several antigen simultaneously, (3) high selectivity, yield and throughput.
Innovative approach to accelerate human cells and organoid-based drug discovery and development process
Human iPS cell has been significantly changing the way of drug research and development process in pharmaceutical industry. Patient-derived iPS cells and disease-causing gene modified iPS cells-derived functional cells, human cells have been widely utilized for phenotypic drug screening, however, additional issues for processing drug development remain to be solved such as target validation of hit compounds, determination of on/off-target effects, assay systems validation due to the differences of the culture condition between the cells on the dish and living tissue and maturity, and clinical translation. Therefore, they would be needed some additional information such as organoid formation and three-dimensional technique and another approached to reproduce disease life cycle in vitro. The demand for the further progress of AI-based effective and efficient analytical method, drug target identification and its strategy remains to be high. Here, we encourage novel proposals of excellent modeling, AI technology, process technology, target identification technology, or feasibility study for human cells and iPS-cell based drug R&D process.
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