Alexandra Abu-Shmais

Alexandra’s project will focus on gaining a better understanding of the fundamental rules of antibody-antigen interactions. Recently our laboratory developed a technology termed Linking B cell Receptor to Antigen Specificity through Sequencing (LIBRA-seq) that enables the rapid identification of antigen-specific B cells. Using this technology, we have successfully identified B cells capable of recognizing antigens encoded within human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus. LIBRA-seq turns BCR-antigen interactions into sequence-able events using DNA barcoding, antigen-specific B cell sorting and single-cell sequencing. As her primary project, Alexandra will leverage the LIBRA-seq technology to construct a human antibody-antigen atlas with specificity towards antigens from a number of common viral pathogens, such as influenza, respiratory syncytial virus, human metapneumovirus, and others. Due to the continuous exposure every person experiences to infection by or vaccination against these common pathogens, antigen-specific B cells can be identified in virtually anyone. Yet, there is still extremely limited information about the repertoires of B cells that different individuals use to recognize these common pathogens and vaccines. With the application of the LIBRA-seq technology, Alexandra will aim to create a high-resolution “atlas” of antibodies and their antigen specificity, resulting in unparalleled depth of information about antibody-antigen interactions. Identified B cells will be produced as recombinant monoclonal antibodies and tested in various assays to define their structural, functional, and other characteristics. Aligned with the CBID goals, this project will entail a variety of biochemical methods, such as protein purification and binding assays, oligonucleotideprotein conjugation, structural biology, and others, in order to gain novel insights into the fundamental rules of antibody-antigen interactions for a variety of pathogens. Furthermore, the outcomes of this proposal may lead to the discovery of novel antibodies of potential therapeutic or vaccine template interest against biomedically relevant agents of infectious disease.

Mentor: Ivelin Georgiev, Ph.D.