The role of the endoplasmic reticulum in regulating T cell function

BACKGROUND
Cellular metabolism critically defines T cell function1-5. How cellular metabolism is orchestrated at the ultrastructural level in immune cells remains largely unknown. Recently, we identified contact sites between the endoplasmic reticulum (ER) and mitochondria as critical subcellular hubs integrating metabolic and signaling requirements in memory CD8+ T cells, specifically underpinning their rapid recall capacity4. This finding established the ER as a critical ultrastructural component selectively enabling a pivotal memory CD8+ T cell feature. Building on this observation, the goal of this PhD Studentship is to assess how basic ER biology links with key aspects of the human CD8+ T cell function.

HYPOTHESIS AND GENERAL AIM
It is our hypothesis that ER-functionality is a critical determinant of T cell immune reactivity, shaping subset specific features. Building on the published work of others, the insight gained from our studies outlined above, and guided by further preliminary data described below - our GENERAL AIM is to establish a structural and molecular map of the ER in human CD8+ T cells and gain mechanistic insight into CD8+ T cell functionalities orchestrated in an ER-dependent manner.

SPECIFIC AIMS
Aim A. Examine ER phenotypes in human naïve and effector memory CD8+ T cells under quiescent conditions and following activation.
Aim B. Interrogate the role of UPR-dependent ER remodeling in activation and effector maturation of CD8+ T cell subpopulations.