John Schwabe
Principal Investigator
Professor John Schwabe leads a research group at the Department of Molecular and Cell Biology at the University of Leicester. The group’s research focuses on understanding enzymes inside the cell nucleus that assemble into large complex molecular machines to regulate genes.
Project in second call:
Biomolecular assemblies in healthy development and cancer
Principal Investigator
Professor John Schwabe leads a research group at the Department of Molecular and Cell Biology at the University of Leicester. The group’s research focuses on understanding enzymes inside the cell nucleus that assemble into large complex molecular machines to regulate genes.
Project in second call:
Biomolecular assemblies in healthy development and cancer
Principal Investigator
Professor John Schwabe leads a research group at the Department of Molecular and Cell Biology at the University of Leicester. The group’s research focuses on understanding enzymes inside the cell nucleus that assemble into large complex molecular machines to regulate genes.
Project in second call:
Biomolecular assemblies in healthy development and cancer
Short Biography
Professor John Schwabe joined the University of Leicester in 2010, and currently holds the position as Director of the Leicester Institute of Structural and Chemical Biology. The current major interest of his research group is understanding the structure and function of HDAC-containing corepressor complexes.
He did his Bachelor’s degree at the University of Oxford, and later earned his PhD at the University of Cambridge in 1992.
AMBER postdoctoral fellowship subject (second call)
Biomolecular assemblies in healthy development and cancer
The nucleus is organized into membraneless, yet functionally distinct compartments. We now know that many nuclear compartments are organized by an array of non-coding RNAs implicated in diverse gene-regulatory processes including embryonic development, cell type-specific phenotypes and cancer. These RNAs acts as hubs/scaffolds for effector proteins forming complex biomolecular assemblies.
Intrinsically disordered regions (IDRs) have recently emerged as key players in the formation of biomolecular assemblies by driving weak, multivalent protein-protein interactions. We have previously identified that the IDRs of the transcriptional corepressor SPEN are essential for protein condensation within large ribonucleoprotein complexes. This supramolecular aggregation is essential for gene regulation. However, how IDR interactions form, their selectivity and contribution to multivalency or how interactions are perturbed in disease remains unclear.
This project will employ a multidisciplinary approach across scales to elucidate the function of these assemblies, their molecular organization, dynamic protein-protein and RNA-protein interactions. We will integrate state-of-the-art methods in stem cell biology and genome editing with super-resolution microscopy, biophysical and structural methods. We will use is silico structure predictions to determine the IDR-containing region(s) that are critical for self-interaction and condensation. We will express minimal RNA-protein assemblies and conduct structural studies by cryo-EM and NMR. We will next perturb these interactions, in vitro through peptide inhibitors which will guide in vivo genetic perturbations followed by downstream analyses within cells by super-resolution microscopy and quantitative image analyses. These pipelines will be significant towards the generation of imaging biomarkers with relevance in dysregulation of biomolecular condensates in cancer.
Project leadership team: Yolanda Markaki (University of Leicester), Cyril Dominguez (University of Leicester), John Schwabe (University of Leicester)
Location: Leicester, UK
Organisation: University of Leicester, Department of Molecular Cell Biology
Links
AMBER call in EURAXESS main call (starting point for application)
John Schwabe's Profile on the University of Leicester website
Department of Molecular Cell Biology, University of Leicester