Marie Skepö

Short Biography

Professor, Docent and Assistant Head of Division of Theoretical Chemistry at Lund University. Research interests include intrinsically disordered proteins (IDPs) and their interaction in solution and to surfaces, utilizing computer simulations in combination with scattering to achieve an understanding of the underlying physics.

AMBER postdoctoral fellowship subject (first call)

Structural investigation of the intrinsically disordered regions of the RNA binding protein Sam68: implication for RNA binding and phosphorylation
(co-PI, Lund Sweden)

Intrinsically disordered regions (IDRs) or protein play crucial roles in almost all cellular functions. Still, the molecular mechanisms that govern their functions remains largely unknown. In recent years, classical structural and biophysical techniques (NMR, FRET, SAXS, ...) have been combined with molecular dynamics simulations to generate structural ensembles and derive the mechanisms of their functions. Sam68 is a typical RNA binding protein that contains a classical folded RNA binding domain flanked by N-terminal and a C-terminal IDRs. While these IDRs have been shown to be crucial for the function of Sam68 and are targets of multiple post-translational modifications, the molecular mechanisms of their contribution remains unknown. Our published (Malki et al, NAR, 2022) and preliminary data clearly show that the Nter and Cter IDRs of Sam68 have the ability to bind RNA specifically and that phosphorylation of a single threonine residue inhibits their RNA binding ability and consequently the cellular functions on the protein.

This raises three important questions:

1- How does an unstructured protein region bind specifically an unstructured RNA? What are the molecular basis for the specificity?

2- How does phosphorylation of a single-amino acid have such an impact on the RNA binding properties of the protein?

3- How does full-length Sam68 recognize specifically its RNA targets

We will answer these questions by combining the team expertise in structural and biophysical methods (NMR, FCS, FRET, SAXS) with molecular dynamics to decipher the structural properties of these regions free, in complex with RNA and following phosphorylation.

Project leadership team: Cyril Dominguez (University of Leicester), Andrew Hudson (University of Leicester), Marie Skepo (Lund University)

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

Marie Skepo's profile in Lund University Research portal

Department of Molecular Cell Biology, University of Leicester

Info about employment at the University of Leicester