The Molecular Machines Visualisation Lab

The central dogma of molecular biology postulates that genetic information flows linearly from DNA, the faithfully maintained blueprint of life, into RNA, the intermediate messenger, onto functional proteins, the machinery of our cells.

DNA, however, is much more than a simple linear code; it is packaged into a complex three-dimensional dynamic structure called chromatin in which DNA is wrapped around proteins known as histones. The compact nature of these structures restricts accessibility to genes. Indeed, 97 per cent of our DNA is packaged as heterochromatin – the dark matter of the genome and is thus inactive at any one time.

Not much is understood about heterochromatin, but its malfunction leads to cancer, developmental defects and susceptibility to infectious diseases.

Our lab seeks to understand the fundamental principles behind the formation, regulation and repair of heterochromatin. We hope to use these insights to discover new druggable targets.

Lab’s mission: Seeing small in a big way.

Lab’s vision: To directly visualise biological processes to enable their functional significance to be understood and, in turn, inform the rational design of new medicines for diseases.

Our lab recently uncovered the molecular function of MORC2, a protein implicated in Charcot-Marie-Tooth (CMT) disease, a debilitating inherited neuropathy. By combining cryo-electron microscopy, biochemical reconstitution, single molecule assay, mass spectrometry and disease-relevant mutations, we elucidated how MORC2 contributes to chromatin architecture and how specific mutations disrupt this function to cause disease. This landmark study provides the first mechanistic insight into MORC2’s role in gene regulation and its connection to neurodegeneration.

For more on this discovery and its implications, see our social media posts:

• Post 1: Discovery overview and scientific highlights

• Post 2: Broader impact and relevance to rare disease communities