合成生物学中的细菌细胞周期 Understanding bacterial cell cycle using synthetic biology

倍增是所有生命形式得以传递延续的内在需求。就细菌细胞而言，在不同的生长环境中，其倍增时间各异，既可以在大约20分钟内完成细胞的倍增，也可能需要数小时才能完成细胞的倍增。本研究方向将结合合成生物学与显微观测、流式细胞分析等单细胞水平的研究方法和经典生化分析、转录组分析、蛋白质组分析等群体水平的研究手段，定量的阐明细菌细胞生长、DNA复制及细胞分裂之间的内在联系的并对相应的分子调控机制进行深入的探讨。 Multiplication is a fundamental requirement for all life forms. The doubling time of bacterial cells varies in different growth environments, ranging from approximately 20 minutes to several hours. The cell size, the amount of DNA content, the initiation time point of DNA replication, and the rate of DNA replication vary with the doubling time. In this project, we will combine synthetic biology with single-cell level analysis, such as microscopy and flow cytometry, and population-level analysis, including biochemistry, transcriptomics, and proteomics. Quantitative observations and analysis will elucidate the interconnections between bacterial cell growth, DNA replication, and cell division and reveal the underlying regulatory mechanisms at the molecular level.

合成菌的肿瘤治疗 Cancer therapy with synthetic bacteria

现有的癌症治疗方法（如放疗、化疗、手术和靶向药物）对中晚期癌症，特别是复发和转移的癌症的效果都不理想。癌症患者存活期短，治疗痛苦大，医疗费用高昂，亟需开发更有效的治疗方法。微生物疗法是通过改造细菌、病毒等微生物，使之携带多种生物模块从而实现识别、治疗肿瘤的复杂机能。本项目的研究，旨在利用合成生物学技术改造细菌，开发能广谱靶向治疗多种实体肿瘤，并能切实抑制其转移和复发的新型治疗方法。 Existing cancer treatments, such as radiotherapy, chemotherapy, surgery, and targeted drugs, are not effective enough for mid- to late-stage cancers, especially recurrent and metastatic cancers. Cancer patients suffer from short survival periods, severe pain due to treatment, and high medical costs. Therefore, the development of more effective therapies for cancer is an urgent need. Microbial therapy aims to recognize and treat tumors by equipping microorganisms such as bacteria and viruses with various therapeutic modules. In this project, we use synthetic biology to engineer bacteria to develop novel therapies that can target a broad range of solid tumors and effectively inhibit cancer metastasis and recurrence.

人工合成多细胞斑图 Synthetic pattern formation

斑图形成指的是系统形成空间有序结构的过程，对于生物体生长发育具有重要意义。用合成生物学方法构建生物斑图是研究斑图形成的重要手段与研究范式，并为未来构造形态结构可控的生物材料、人工组织器官提供了可能性。本研究方向将建立数学模型，系统研究斑图形成所依赖的拓扑结构，设计基因线路，构建基因线路与菌株。本项目的完成将阐明细菌空间扩张过程中斑图的产生机制，揭示生物斑图的设计原理。 Pattern formation refers to the generation of regular spatial structures and plays essential roles in the development of organisms and ecosystems. Reconstructing biological patterns with synthetic biology allows us to simplify and control the systems, providing a new tool and research paradigm for studying pattern formation. The design and construction of biosystems with spatial patterns also provides the possibility of synthetic biomaterials, tissues, and organs with controllable spatial structures. The aim of this project is to elucidate the design principle of pattern formation. In this project, we will develop mathematical models to systematically investigate the system topologies that allow pattern formation during the range expansion of bacteria. Based on the quantitative predictions of modeling, we will design gene circuits and engineer synthetic bacterial strains.

Grants