Ciulli Laboratory

School of Life Sciences, University of Dundee

Chemical & Structural Biology of Protein-Protein Interactions

We are broadly interested with understanding and exploiting the ligandability of protein-protein interactions (PPIs) and protein surfaces within complex biological systems. Of particular interest are protein interfaces recognizing protein Post-Translational Modifications (PTMs). We employ a question-driven, multi-disciplinary approach that combines chemical, biophysical and structural techniques with the concepts of fragment-based drug design. Current research efforts are directed towards targeting PPIs and PTM recognition within protein families of biological and medical relevance within the Ubiquitin and Chromatin systems:

1) the Cullin RING E3 ubiquitin ligases (CRLs) multisubunit complexes

2) a family of multidomain proteins containing paired chromatin reader domains

We seek to understand the chemical nature of the surfaces and intersubunit interfaces of these proteins, and to exploit their tractability and selectivity toward small molecule modulation. The ‘chemical probes’ we design and develop are evaluated biophysically, structurally and inside living cells as tools to address biological questions.