Cell polarity is critical for diverse processes including migration, asymmetric division, and tissue development. One of the major regulators of cell polarity and asymmetric division is a network of polarity proteins that has been conserved across evolution. The regulation and functional consequences of cell polarity have been well studied in model organisms such as budding yeast, C. elegans, and Drosophila, but are not well understood in mammalian cells. In the mammalian immune system, a T lymphocyte undergoes a substantial reorganization and polarization after encountering an antigen-presenting cell bearing microbial components during an infectious challenge. The conserved polarity complexes are among the cellular components that undergo reorganization, but how they regulate T lymphocyte fate specification and function remains unknown. This proposal draws from the disparate disciplines of cell biology, developmental biology, and immunology to test the hypothesis that cell polarity regulates (1) the generation of effector and memory T lymphocyte subsets from their naive predecessors as well as (2) the execution of effector T lymphocyte function. Accomplishment of the aims proposed herein is likely to yield important insights about the fundamental mechanisms by which regulators of polarity influence cell fate specification and function, and may help to provide a framework for the rational development of vaccines.

Public Health Relevance

Effector and memory T lymphocytes are cells of the immune system that provide protection against microbes. Our goal is to understand how these cells are generated and how they function. These studies may help our efforts to improve vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI095277-03
Application #
8580193
Study Section
Cellular and Molecular Immunology - B Study Section (CMIB)
Program Officer
Kelly, Halonna R
Project Start
2011-12-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
3
Fiscal Year
2014
Total Cost
$330,228
Indirect Cost
$105,228
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Jung, Hong-Ryul; Song, Kwang Hoon; Chang, John T et al. (2014) Geometrically controlled asymmetric division of CD4+ T cells studied by immunological synapse arrays. PLoS One 9:e91926