ARTificial Tumour Immune MicroEnvironment for structured profiling of cancer immune adaptation

在ART-TIME的框架内，我将为人类胰腺癌有机物开发一个人工肿瘤免疫微环境(ART-TIME)，以支持对肿瘤免疫适应的结构化和理性分析。因此，免疫细胞，免疫微环境的决定性因素，将通过自下而上的组装，从它们的单分子构件重新创建为合成细胞。可编程的合成细胞将被引入肿瘤有机物中，作为逼真的白细胞模拟呈现免疫效应功能。通过这一方法，将首次在肿瘤模型内创建分子定义的免疫环境。基于成像的多参数筛查将评估器官发育和免疫治疗反应，作为ART时间配置的函数。这一策略将把时间结构与癌症免疫适应和逃避联系起来，以定量描述治疗耐药性。因此，ART-TIME努力解开肿瘤免疫微环境的动态复杂性，走向理性的解剖。此外，艺术时间将为混合生物材料的组装提供概念，这些材料体现了活细胞的基本特征。在这个由Michael Dustin教授在牛津大学主持的奖学金中，我将使用可编程的人造材料贡献肿瘤免疫学的基础知识。我的地理位置转变为一个拥有以临床为导向的基础设施的研究环境，这将极大地扩展我的科学视野，完善我的学术形象。我在自下而上的合成生物学方面的专业知识和主持人在免疫学方面的高质量研究之间的协同作用使我受益匪浅，这个跨学科项目将为合成细胞打开广阔的前景，能够通过在生物和非生物世界之间正在消失的边界创造杂交材料来操纵组织模式-这是我后来研究生涯的设想重点。

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.