Service Project #3: Biomaterials-Based Germinal Center Niches for Understanding the B Cell Maturation and B Cell Receptor Signaling

Collaborating Investigator: Ankur Singh
Affiliation: Georgia Institute of Technology
Funding Status: NIH
Project Period: 02/09/18 – 01/31/24

Summary

The goal of SP #3 is to develop a biomaterials-based modular ex vivo organoid platform with the ability to generate high affinity, antigen specific antibodies ex vivo. Such tissue models can also be used to improve the mechanistic understanding of mechanisms that regulate germinal center (GC) B cells. NIM technologies from TR&D2 will be utilized to further these goals by delivering DNA and RNA agents to precisely tune gene expression and signaling within the organoid platform. This application highlights the use of NIMs as enabling immunoengineering tools for in vitro / ex vivo research.  

Approach

Engineering designer organoids with tunable ligand specificities, understanding the antigen specific immune response, and establish a link between integrin ligand specificity and cell cycle epigenetics of germinal center reaction.  

NIMs will be synthesized as described in TR&D2 Specific Aim 1 and sent to GA Tech for evaluation and use in pursuing their goals. The ability for efficient, safe, and targeted intracellular delivery to immune cells is an important technology to modulate the surface expression and secretion of key immunomodulatory molecules. This project will enable the NIM library to be evaluated and optimized for transfection of B cells. Building off the technology in TR&D2 Specific Aim 3, NIMs can be sent to enable ligand-specific uptake and intracellular delivery to B cells.  The results of this work will broaden the applications of the technology to include B cells and also highlight their utility as an ex vivo research tool. 

TRD