DNA structures captured in ‘exquisite detail’ using new technique

Scientists have discovered a way to look at how DNA functions inside living cells, paving the way for techniques to pinpoint how changes can lead to illnesses such as heart disease and cancer.

The method captures how genes are controlled “in exquisite detail”, researchers said.

Academics suggest the findings represent a “critical step” in understanding how genes work, what goes wrong in disease, and what can be done to fix it.

The human genome, made of DNA, is the complete set of genetic instructions found in the control centre – the nucleus – of the cells in the body.

It comprises about 3.2 billion base pairs of DNA per cell, packed in a microscopic space, and would measure around two metres if stretched out.

Within this tiny space DNA constantly bends and loops into 3D structures that determine which genes become active or silent, similar to a circuit board.

Until now, experts could only look at these interactions in low resolution.

Scientists at the University of Oxford’s Radcliffe Department of Medicine have developed a new technique known as MCC Ultra.

This has allowed them to capture the smallest unit of DNA, known as a single base pair.

Lead author Professor James Davies said: “For the first time, we can see how the genome’s control switches are physically arranged inside cells.

“This changes our understanding of how genes work and how things go wrong in disease. We can now see how changes in the intricate structure of DNA leads to conditions like heart disease, autoimmune disorders and cancer.”

The Oxford scientists collaborated with Professor Rosana Collepardo-Guevara of the University of Cambridge on the study, which is published in the journal Cell.

The team suggests the research could pave the way for scientists to pinpoint where gene regulation goes wrong, and how it may be corrected.

Their new model of gene regulation proposes that cells use electromagnetic forces to bring DNA control sequences to the surface, where they form clusters of activity that were previously invisible.

The study suggests these structures are crucial in how cells read their genetic instructions.

Hangpeng Li, a doctoral researcher who led the experimental work, added: “We now have a tool that lets us study how genes are controlled in exquisite detail.

“That’s a critical step toward understanding what goes wrong in disease, and what might be done to fix it.”