Project Title: Multi-modal, deep single cell and proteomic analyses of patients and vaccinees to dissect disease mechanisms and identify biomarkers
NIAID Principal Investigator: John S. Tsang Ph.D.
Chief, Multiscale Systems Biology Section, (LISB)
Co-Director, NIH Center for Human Immunology (CHI)
Can systems immunology provide a predictive understanding and detailed molecular and cellular view of the immune response to SARS-CoV-2 infection?
The Multiscale Systems Biology Section of the Laboratory of Immune System Biology (LISB) will integrate computational approaches and several cutting-edge high-throughput methods to assess changes in the epigenome, transcriptome, and proteome throughout the course of COVID-19 disease. Using CITE-seq, they will simultaneously interrogate the immune cell surface proteome, transcriptome, and B-cell receptor (BCR)/T-cell receptor (TCR) repertoire at the single cell level of peripheral blood mononuclear cells (PBMCs) over the course of infection and convalescence. To complement this experiment, whole-blood RNA-seq will provide information on the transcriptome in neutrophils in addition to PBMCs. To understand the epigenetic and transcriptional network underpinnings of these cellular responses, single cell ATAC-seq will be used and integrated. High-parameter proteomics using a Somalogic panel measuring approximately 5,000 proteins will be used to deeply profile the circulating proteome. In addition, similar approaches will be used to assess the molecular and cellular responses of the immune system over the course of clinical trials to test experimental vaccines and therapeutics including remdesivir. They will also examine if pregnancy affects response to SAR-CoV-2 infection. The Multiscale Systems Biology Section are experts in using machine learning and computational modeling approaches to integrate such multi-modal data to better understand the immune system’s role in disease and protection. They hope to find predictors of infection response severity, which may help pre-identify patients with increased risk of severe symptoms. Elucidating the molecular and cellular networks that orchestrate the immune response to infection could also serve to identify targets for therapeutic intervention. Furthermore, comparing the new data on COVID-19 to existing data on other respiratory infections such as flu, SARS-CoV, or MERS as well as other immune-mediated diseases may pinpoint reusable drug targets. All results will be integrated with the data from the other Immune Response to COVID-19 research projects, such as host genetics, serology, deep immune repertoires, and clinical measurements.
- Helen Su, M.D., Ph.D.
- Luigi Notarangelo, M.D.
- Raphaela Goldbach-Mansky, M.D, M.H.S
- Mihalis Lionakis, M.D., Sc.D
- Jeffrey Cohen, M.D.
- Richard Davey, M.D.
- Daniel Chertow, M.D., M.P.H.
- Yasmine Belkaid, Ph.D.
- Andrea Lisco, M.D, Ph.D and Irini Sereti, M.D
- Vaccine Research Center
- Center for Human Immunology
Université Libre de Bruxelles
1-2 million cryopreserved PBMCs, 2 mL of EDTA-blood pellet frozen in serum + 10 % DMSO, and 100 µL of serum or plasma is required for use in all of the methods. Ideally samples would be taken 1) upon hospital admission, 2) during hospitalization, 3) at discharge, and 4) after discharge.