AI design of molecular binders against the Wnt signalling pathway

• PhD and Graduate Research Masters
• Honours

Wnt signalling is an evolutionarily conserved pathway found across all animal phyla. It spatially organizes multicellular organisms during embryonic development, driving cell polarization, cell fate, and regulating cell proliferation and migration. Its critical role in cellular growth and development makes aberrant Wnt activation a significant driver of many cancers. Despite its therapeutic potential, developing selective Wnt inhibitors remains challenging.

Advances in artificial intelligence (AI) offers innovative opportunities to discover novel molecular binders that target the Wnt pathway. This project will leverage AI driven approaches to design molecular binders against the Wnt signalling pathway. Our methodology will combine in silico design of binders with subsequent experimental validation through functional assays and structural biology techniques.

The Glukhova laboratory is based in WEHI’s structural biology division and combines cryo-electron microscopy and x-ray crystallography with biochemical, biophysical, and pharmacological assays to gain insights into the atomic-level details of individual proteins as well as large complexes involved in Wnt signal transduction.

Our research focuses on decoding the molecular architecture of Wnt pathway components, from initial ligand-receptor interactions to downstream signaling events. While Wnt signalling represents a promising target for cancer therapeutics, its fundamental role in tissue homeostasis presents significant challenges for developing selective interventions. Through detailed structural and functional analyses, we aim to identify precise molecular vulnerabilities that could enable targeted therapeutic approaches while minimizing disruption to essential Wnt functions in healthy tissues.