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About the project
There is a significant need for developing reliable human organ representations (termed organoids) for drug development, personalized drug testing, and on the longer run for organ transplantations. The advent of induced pluripotent cell (iPSC) technology has allowed developing in vitro human organoids that show features of the organs they represent, but are significantly less structured and less mature than their human counterparts. The field therefore requires high-content tracking tools and algorithms to guide organoid development. Developing such technologies will represent a leap towards reliable personalized organoids with organ-like histology and functionality.
Confocal Raman microscopy allows label-free visualization of a plethora of molecules, including morphogenetic signals in fixed and living specimens. Because Raman spectroscopy is quantitative it can be coupled to computational algorithms to provide spatially resolved life tracking markers. Multivariate Raman spectra deconvolution on morphogenetic signals and coupled processes, will be potentiated by correlating Raman spectroscopic imaging with high-resolution spatial transcriptomics and desorption electrospray ionization-mass spectrometry (DESI-MS).
We will in parallel develop methods for fast and slow time-lapse imaging of cells in the organoids and by coupling spatio-temporal feature extraction to chemical and physical phenomena, and develop statistical physics models for organ/organoid pattern formation in vitro. The information will be used to tailor statistical models to improve organoid formation in vitro. The described technologies will be developed using in the first iteration zonated liver organoids and benchmarked to human liver slices. In a second iteration we will apply the technology to in vitro differentiated gastruloids/inductoids (lineage restricted vascularized embryonic structures comprising endoderm and mesoderm while lacking most of neuroectoderm) benchmarked to mouse embryos. They serve as a strategy for developing complex organ representations by embryonic processes with the future outlook of translation the strategy to the human situation to achieve better human organ representations (beyond the scope of this proposal).
Primary objective
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To improve organoid development by developing and applying correlative imaging and data analysis technologies that track morphogenetic progresses.
Secondary objectives
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Development of Raman spectroscopy in correlation with spatial transcriptomics and DESI-MS as an enabling tracking technology.
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Development of Perturbation-imaging techniques to map force and motion patterns as an enabling tracking technology
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Development of physical and statistical models that can feed into organoid development