Quantitative modeling of the phenotypic variability of individual T cells and the

我们的长期目标是从理论和实验上探索如何可靠地免疫 从个体T的不可靠响应中出现的系统级别的响应 细胞。 我们的第一个项目旨在探索基因表达水平的异质性 关键信号蛋白在T细胞应答中产生表型变异 配基。我们还将探讨信号响应的这种随机性如何转化为 功能表型变异。 我们的第二个目标是测试多路信号(例如T细胞配体和IL15 细胞因子)可以激活信号串扰，从而调节KEY的水平和/或活性 信号转导蛋白，并使T细胞对自身衍生的配体反应强烈。 我们的第三个目标是探索细胞因子调节如何在抗原中整合细胞变异性。 在单个细胞水平上对受调控的集体反应的反应。这个项目 重点关注白介素2作为控制群体感应的关键细胞因子 效应T细胞和调节性T细胞的抑制。 我们的方法基本上是跨学科的，伴随着计算 建模和实验测试。它包括建立和验证理论 量化和控制免疫反应如何动态出现的预测--以及 单个T细胞的集体调节特性。

Our long-term goal is to probe theoretically and experimentally how reliable immune responses emerge at the system level from the unreliable responses of individual T cells. Our first project aims at probing how heterogeneity in the expression levels of key signaling proteins generates phenotypic variability in T cells' responsiveness to ligands. We will also probe how such stochasticity of signaling responses translates into functional phenotypic variability. Our second aim tests how multiplexed signals (e.g. T cell ligands and IL15 cytokine) can activate signaling crosstalks that modulate the levels and/or activity of key signaling proteins and make T cells hyperresponsive to self-derived ligands. Our third aim probes how cytokine regulation integrates cell variability in antigen response at the individual cell level towards a regulated collective response. This project focuses on Interleukin-2 as a critical cytokine that controls quorum sensing among effector T cells and suppression by regulatory T cells. Our approach is fundamentally interdisciplinary with concomitant computational modeling and experimental testing. It consists in making and validating theoretical predictions to quantify and control how immune responses emerge as dynamically- and collectively-regulated properties of individual T cells.