Development of novel methods for identifying disease markers using in vitro disease model cells
Identification of specific disease markers is very useful for the "early detection" of diseases. In recent years, the application of genome editing technology and disease-specific iPS cells enabled the generation of cell lines that reflect many pathological conditions. Therefore, these cell lines may be useful as a new approach for identifying disease markers.
In this category, Takeda is seeking exploring research for disease markers and the proposal of a method of verification using disease model cells regardless of the pathology type. The areas of interest include but are not limited to:
Dysfunction of parvalbumin (PV) interneurons is one of the key factors to induce cognitive impairment in psychiatry disorders (e.g. schizophrenia, autism spectrum disorder). Human induced pluripotent stem cells (hiPSC)-derived neurons are widely used because they can be derived from patients' cells. On the other hand, there are still issues regarding purity and maturation in generation of hiPSC-derived PV interneurons. Here, we would like to recruit projects that aim to establish high efficient differentiation method of human iPSC-derived parvalbumin interneurons.
Many familial type mutations have been identified in neurological disorders. In some cases of familial type mutations, the penetrance rate is about 100%. But, there are a few cases of asymptomatic carriers who do not develop diseases. We are looking for the project identifying novel compensatory mechanisms against disease development by analyzing rare asymptomatic carriers with clinical samples such as blood cells and iPS cells of them and their relatives.
Areas of interest:
Neuronal/Brain organoids have the potential to become highly translatable disease models. We are seeking a phenotypic screening system by leveraging organoid technology to conduct patient-centric drug discovery for neurodegenerative diseases. To pursue this opportunity, we are also focusing on the improvement of organoid generation technologies and that of functional analysis technologies. We call for ideas regarding Neuronal/Brain organoid research:
Target identification and biomarker discovery are important steps for phenotypic assay based drug development. For those activities, proteomics analysis is a powerful tool, however, conventional proteomics analysis uses more than sub mg of total protein (1x10＾6 cells~) as material. Because of that, it requires a lot of time and cost especially when the targeting materials are iPS cells or extracellular vesicles such as exosomes that are hard to prepare in a large scale. Here we seek technology that enables ultra-high sensitive proteomics analysis, such as single-cell proteomics, to achieve the target identification and biomarker analysis with trace amount of biological materials.
Nucleic acid medicine such as an antisense oligonucleotide, siRNA, and aptamer is well known as a new modality which could target "undruggable target" for conventional drug modalities (i.e. small molecules, mAb, etc.) We expect the innovative idea with novel mechanism of action and technology platform leading to oligonucleotide therapeutics.
Recently, application of oligonucleotide therapeutics to neuropsychiatric disorders is highly anticipated. However, oligonucleotides cannot cross the blood-brain barrier, which is a big hurdle for the development of nucleic acid medicine. Thus, a platform which can effectively deliver oligonucleotide into brain, especially to specific brain cells such as neuron, microglia and astrocytes, is needed. We expect the innovative idea on technology platform to overcome these challenges.
We are recruiting research themes to bring about breakthroughs in neuroscience drug discovery, including, but not limited to, the following examples.
Drug discovery research on tough targets
(e.g.) biased- or heterodimer-selective GPCR ligands, allosteric ligands, phosphatase inhibitors, and protein-protein interaction modulators
Drug discovery research based on innovative mechanism of action
(e.g.) protein degradation inducers, ligands acting on RNAs (incl. splicing modulators), and small molecule chemical chaperones
We are recruiting research themes to combat issues in drug discovery using new modalities, including, but not limited to, the following examples.
We are recruiting research themes to improve and/or accelerate the drug discovery process, including, but not limited to, the following examples.
Development of novel drug discovery algorithms based on artificial intelligence and/or molecular simulation
(e.g.) pharmacological activity and/or adverse effect prediction, and design of novel compounds
Drug discovery research based on phenotypic screening
(e.g.) innovative technologies for cellular high throughput screening, novel methods for target identification, and novel methods for compound optimization (incl. methods toward small molecules from hits with medium/high molecular weight, such as natural compounds)
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