Yolanda Markaki

Short Biography

Dr Yolanda Markaki joined the University of Leicester in 2022, and leads a group at The Department of Molecular and Cell Biology. Her research group is interested in deciphering fundamental principles that govern genome architecture and to explore how changes in nuclear compartmentalization and the distribution of epigenetic factors alter gene expression and cellular fate.

Prior to her current position, she was a postdoctoral researcher at Ludwig-Maximilians-University of Munich (2010-2016).

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)

Guide for applicants

Yolanda Markaki's Profile on the University of Leicester website

Department of Molecular Cell Biology, University of Leicester

Info about employment at the University of Leicester