ARTificial Tumour Immune MicroEnvironment for structured profiling of cancer immune adaptation

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Within the framework of ART-TIME, I will develop an artificial tumour immune microenvironment (ART-TIME) for human pancreatic cancer organoids empowering structured and rational analysis of tumour immune adaptations. Immune cells, the defining elements of an immune microenvironment, will thus be recreated as synthetic cells by bottom-up assembly from their single molecular building blocks. The programmable synthetic cells will be introduced into tumour organoids to function as lifelike leukocyte mimics presenting immune effector functions. By this, a molecularly defined immune environment will be created inside tumour models for the first time. Imaging-based multi-parametric screenings will assess organoid development as well as immunotherapy response as a function of the ART-TIME configuration. This strategy will link TIME architectures to cancer immune adaptation and evasion for quantitative description of therapy resistance. Therefore, ART-TIME strives to de-convolute the dynamic complexity of the tumour immune microenvironment towards a rational dissection. Moreover, ART-TIME will contribute concepts for the assembly of hybrid biomaterials that embody essential features of living cells. Within this fellowship, hosted at the University of Oxford by Prof. Michael Dustin, I will contribute fundamental knowledge on tumour immunology using programmable man-made materials. My geographic transition into a research environment with clinically oriented infrastructure will significantly expand my scientific horizon and refine my academic profile. Greatly profiting from the synergy between my expertise on bottom-up synthetic biology and the host's highquality research on immunology, this interdisciplinary project will open up broad perspectives for synthetic cells capable of manipulating tissue patterns by creating hybrid materials at the vanishing boarders between the living and non-living world - the envisioned focus of my subsequent research career.