Our group uses an integrative structural biology approach to uncover the molecular mechanisms underlying gene expression, pre-mRNA splicing and their regulation. We combine cutting-edge electron microscopy and imaging technologies with biochemistry, biophysics and cell biology to investigate the structure, function and dynamics of macromolecular complexes across multiple scales. 

Research Summary

A major focus of our research is on large and dynamic RNA–protein complexes involved in pre-mRNA splicing, snRNP biogenesis and RNA 3′-end processing. We combine single-particle cryo-electron microscopy (cryo-EM) with genome engineering, biochemical reconstitution and quantitative biophysical approaches to capture these molecular machines in different functional states and understand how their structure and dynamics enable their biological functions. 

We are particularly interested in bridging the gap between the detailed molecular information obtained from purified complexes and their organisation and function within the cellular environment. To achieve this, we use in situ structural biology approaches, integrating cryo-electron tomography (cryo-ET), correlative light and electron microscopy (CLEM) and computational approaches to visualise molecular machines directly within cells. 

Future Goals

Our research is driven by biological questions and cutting-edge structural biology technologies. We therefore continuously adopt and develop emerging experimental and computational approaches that allow us to investigate increasingly complex and dynamic molecular systems. Ultimately, we aim to understand how the molecular machines responsible for RNA processing are assembled, regulated and organised within cells, and how their dysfunction contributes to human disease.