Gideon Schreiber Lab

Protein-Protein Interaction

Research

My laboratory is engaged in understanding the intricate web of protein-protein interactions that underpin every aspect of living organisms. With a sharp focus on the structural and functional nuances of these interactions, our research unravels the molecular dialogue that governs biological signaling. We employ a multifaceted, interdisciplinary strategy that seamlessly integrates protein engineering and bioinformatics. These tools act as pivotal inputs to address complex biological queries. Among our key research themes is a comprehensive elucidation of the interferon signaling pathway—a crucial component of immune response. Moreover, we engaged in tracking the evolutionary journey of the SARS-CoV-2 virus, providing vital insights into pandemic progression and viral behavior. Our most recent endeavor involves the pioneering design of specialized exosomes. These are engineered with precision to transport RNA molecules, opening new vistas in the realm of therapeutic delivery systems. Each discovery propels us closer to decoding the language of life's molecular machinery, which brings us closer to treat diseases in a specific manner.

Research page

Cytokine signaling as a cascade of protein interactions for multiple outputs

Structure/function & evolution of protein interactions towards drug design

Targeted delivery of RNA using engineered exosomes

Investigate the role of interferons in CLL and Melanoma in mouse models

Selected Publications

Structure–function of type I and III interferons

de Weerd N. A., Kurowska A. K., Mendoza J. L. & Schreiber G. (2024) Current Opinion in Immunology. 86, 102413.

Type I and type III interferons (IFNs) are major components in activating the innate immune response. Common to both are two distinct receptor chains (IFNAR1/IFNAR2 and IFNLR1/IL10R2), which form ternary complexes upon binding their respective ligands. This results in close proximity of the intracellularly associated kinases JAK1 and TYK2, which cross phosphorylate each other, the associated receptor chains, and signal transducer and activator of transcriptions, with the latter activating IFN-stimulated genes. While there are clear similarities in the biological responses toward type I and type III IFNs, differences have been found in their tropism, tuning of activity, and induction of the immune response. Here, we focus on how these differences are embedded in the structure/function relations of these two systems in light of the recent progress that provides in-depth information on the structural assembly of these receptors and their functional implications and how these differ between the mouse and human systems.

Harnessing the power of IFN for therapeutic approaches to COVID-19

G. V. E., E. B. S., C. D. D., Gideon S. & Mirko P. (2024) Journal of Virology. 98, 5, e01204-23.

Interferons (IFNs) are essential for defense against viral infections but also drive recruitment of inflammatory cells to sites of infection, a key feature of severe COVID-19. Here, we explore the complexity of the IFN response in COVID-19, examine the effects of manipulating IFN on SARS-CoV-2 viral replication and pathogenesis, and highlight pre-clinical and clinical studies evaluating the therapeutic efficacy of IFN in limiting COVID-19 severity.

Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant

Uriu K., Ito J., Zahradnik J., Fujita S., Kosugi Y., Schreiber G. & Sato K. (2023) The Lancet Infectious Diseases. 23, 3, p. 280-281

All Publications