Structural Studies of a T cell Specific Tyrosine Kinase

Summary

This project aims to study the TEC kinase ITK's role in tuning T-cell signaling, specifically how ITK activation mechanisms and costimulatory interactions mediate tunable responses to TCR stimulation, and its role in human diseases like autoimmunity and lymphomas.

What they want

The proposal will study the contribution of specific ITK activation mechanisms (Aim 1) and costimulatory interactions (Aim 2) to understand how ITK mediates tunable responses to TCR stimulation. Biochemical and structural biology insights will be directly transferred into primary T cell experiments to elucidate the molecular mechanisms controlling ITK regulation. The project will also study the role of ITK regulation in human disease (Aim 3), including genetic mutations activating ITK in autoimmunity and the interaction of ITK-SYK fusion tyrosine kinase with normal ITK in promoting oncogenesis in peripheral T cell lymphomas.

Deliverables

Understanding of specific ITK activation mechanisms
Understanding of costimulatory interactions' contribution to ITK-mediated responses
Elucidation of molecular mechanisms controlling ITK regulation
Study of ITK regulation's role in human disease (autoimmunity, lymphomas)

Technical requirements

Biochemical studies
Structural biology insights
Primary T cell experiments