Investigation of Immune Cell Trafficking in Complex Cellular Environment

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BACKGROUND: Immune cell trafficking is fundamentally important for the biology of immune cells with direct relevance to physiological processes. The trafficking of immune cells is orchestrated by various microenvironmental factors such as chemical concentration gradients and electric fields (EF). Cell migration directed by electrochemical fields have been well demonstrated in vitro and in vivo. However, the underlying mechanisms are far from being well understood. Particularly, there is a lack of knowledge about how immune cells migrate in response to complex environmental guiding signals that are inter-coupled and dynamically vary in space and time. My previous studies through the Discovery grant identified the interesting CCR7-mediated combinatorial guiding mechanism for T cell migration, the migratory memory effect of immune cells in chemical fields and EF, and migratory interactions between different cell types in complex guiding microenvironment, which motivated further explorations. LONG-TERM GOAL: My Discovery research program aims at integrating cell biology and immunology research approaches, biophysical analysis and novel microfluidic tools to achieve a better understanding of immune cell trafficking in complex cellular environments. NEXT FIVE-YEAR RESEARCH PLANS: My Discovery research program in the next 5 year will critically investigate the fundamental mechanisms for immune cell migration and cell-cell interactions in complex electrochemical guiding environments through the following objectives: Objective I: Investigate CCR7-mediated guiding mechanism for T cell migration in complex chemoattractant fields. The focus is to better understand how T cell migration is mediated by 1) co-existing fields of CCR7 ligands and Sphingosine-1-phosphate; 2) co-existing fields of CCR7 ligands and CXCL13. Objective II: Examine the memory effect of immune cell migration in electrochemical fields. In this direction, I will research 1) the impact of spatiotemporally varying chemical fields on immune cell migration; 2) immune cell migratory behavious in response to dynamically changing EF. Objective III: Explore cell-cell migratory interactions in electrochemical fields. I will direct this part of my research program to explore how cell-cell migratory interactions are mediated 1) by EF alone; and furthermore 2) by co-existing chemical fields and EF. SIGNIFICANCE: This work will contribute significantly to the understanding of the complex process of immune cell migration and trafficking. Importantly, the interdisciplinary training through my Discovery program will develop young scientists able to conduct research at the interfaces of physical sciences, engineering and life sciences. In addition to acquiring a solid scientific backgrounds in cell migration, the students will be trained for hands-on research skills and develop strong scientific communication ability thereby preparing them for careers in both academic and industrial sectors.