研究概述

课题组聚焦干细胞、免疫细胞、及肿瘤细胞的异质性及细胞命运决策机制。通过发展新型的定量单细胞实验与分析技术,并结合系统生物学方法与合成生物学手段,在单细胞水平上研究细胞异质性及命运决策的关键调控要素,以期在单细胞水平上深入理解发育、免疫、疾病等重要过程,并进一步利用药物或合成生物器件对这些过程进行精准干预。

研究方向

1、Analyzing cell-to-cell variability in time

Single-cell analysis tools have revolutionized many disciplines of biology. Yet, despite the growing single-cell data, we often lack a temporal view of how cells maintain homeostasis or how they respond to environmental signals at the individual cell level. Temporal analysis of single cells is critical for understanding the mode, mechanism, and function of cell-to-cell variability.

2、Deciphering regulatory principles by profiling transcription factor dynamics

An important mechanism accounting for the variability among cells is the regulatory dynamics, particularly the activity dynamics of transcription factors (TFs). We have been interested in two areas of research related to TF dynamics: the profiling of TF dynamics across systems and conditions, and the functional roles of TF dynamics in development, differentiation, and immunity.

3、Toward robust and predictable cellular programming

Programming mammalian cells and tissues with synthetic biological devices faces two key challenges: 1) individual cells in a tissue are highly heterogeneous, exhibiting different responses to the same input; 2) synthetic devices often fail to operate as designed due to interferences from the host cell. We are working on addressing both challenges through data-driven rational design as well as high-throughput screening.

研究成果概述

代表性成果一:动态转录调控新模式新机制

代表性成果二:新型哺乳动物合成转录因子

代表性成果三:哺乳动物细胞连续定向进化工具开发及应用

Ma L and Lin Y, Nat Chem Biol. 2025