systems biology of Lassa and Ebola infection
Viral hemorrhagic fevers, of which Ebola virus (EBOV) and Lassa virus (LASV) are prototypical examples, are a major source of global human suffering. The mission of the recently established Center for Viral Sytems Biology (CViSB) is to identify molecular networks of host and viral factors that determine the outcome of infection with EBOV and LASV. The Briney lab, which leads the CViSB’s Technology Core, serves as the data generation hub of the CViSB. We utilize a variety of cutting-edge omics technologies and high-throughput functional screening to deeply characterize the host immune response to EBOV and LASV infection. In addition, we are pioneering the development of emerging single-cell analysis techniques to rapidly produce comprehensive molecular profiles of individual antigen-specific immune cells.
We’re currently looking for talented, motivated individuals to join the CViSB team! Check our jobs page for more information
the baseline human antibody repertoire project
The human antibody repertoire is vast and complex, containing sufficient diversity to mount an immune response against virtually any target antigen and also encode a comprehensive molecular record of previous pathogen encounters. A major focus of our lab is to leverage the massive advances in genomics techniques, with particular focus on high-throughput single-cell analysis methods, to deeply characterize the development and maturation of the human antibody repertoire.
Early B cell development occurs in the bone marrow and entails somatic recombination of the antibody heavy and light chains, negative selection of self-reactive clones, and positive selection for proper B cell receptor (BCR) function. We have recently reported that the circulating B cell repertoires of different individuals are far more similar than would be expected given the very low likelihood of coincidently similar V(D)J recombinations. Some have speculated that this similarity is primarily due to convergent responses to commonly seen pathogens (CMV, for example), but we have evidence that the greater-than-expected repertoire similarity is more likely due to the repertoire shaping effects of selection during early B cell development.
We’re using advanced genomics and bioinformatics tools to study, in great detail, the effects of early selection on the developing antibody repertoire by combining single-cell RNA-seq, paired HC/LC sequencing, and bulk antibody repertoire sequencing into a single, integrated dataset that spans repertoire development and maturation.