Graduate Student Seminar Series – Farshad Murtada
Graduate Student Seminar Series
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Location: MS2158 – 1 King’s College Circle
Presentation Title: Capturing T Cells using DNA Nanostructures for Immunotherapy and Diagnostics
Abstract:
Background: T cells are immune cells that have capability to directly kill infected or cancerous cells by binding to specific short protein molecules, called “antigens” displayed on the surface of these cells. Each T cell has a unique T cell receptor (TCR, i.e. they are clonal) that recognizes specific antigens as a part of a larger protein-complex, called the major histocompatibility complex (MHC). T Given the role of T cells in immune response, identifying the antigen specificity of T cells and enumerating their quantity in clinical samples has many important benefits. These include: 1) diagnosis and monitoring the progression of diseases, including auto-immune diseases, infections, and cancer; 2) assessing correlates of protection against a particular disease; and 3) develop immunotherapies, such as adoptive cell therapies.
Problem: The industry standard for antigen-specific T cell detection and isolation uses pMHC tetramers conjugated with a fluorophore followed by fluorescence activated cell sorting (FACS) This technology has two limitations: (i), they fail to detect T cells with low affinity TCRs towards their cognate antigen, due to the rapid fall off-rate of the pMHC tetramer; (ii) only a small fraction of different antigen-specific T cells can be detected from a single sample because the number of spectrally distinguishable fluorophores are limited. This is a major limitation because in many therapeutic applications, antigen identity is unknown and can only be identified via screening a library of hundreds of putative antigens. The limited number of fluorescence-based tetramers make such a screen unfeasible.
Project Objective: To use DNA origami nanostructures to develop a novel reagent for the isolation of antigen-specific T cells with enhanced binding and detection throughput (i.e. screen of hundreds of different antigen species within a single sample).
Supervisor Name: Leo Chou
Year of Study: 4
Program of Study: PhD
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