Greg’s team aims to understand which genetic changes, or variants, predispose people to diseases such as cancer. They have developed methods to systematically edit the human genome at scale, by engineering all possible variants in genes linked to disease to reveal how they affect human health.

Until now, researchers in the field have mostly focused on mutations in areas of genes that provide the blueprint for making proteins, known as coding regions. But 98% of the human genome is composed of non-coding regions, long stretches of DNA that aren’t used to make proteins but have important regulatory roles. The new funding will allow Greg’s team to systematically search for mutations underlying disease in these ‘dark’ areas of our genome. 

Because non-coding regions are so long, the team will first use an AI-based risk-scoring computer model to identify which variants in non-coding regions are most likely to cause disease. 

Next, high-priority variants will be introduced into human cells to test whether they change how genes are regulated. For this, a technique called prime editing will be used that allows 100,000 variants to be tested in a single batch. Variants found to impact important genes will be scrutinised using data from international patient cohorts to reveal new links to disease. 

The ultimate goal of the work is to learn the underlying logic of how mutations impact non-coding regions by amassing vast amounts of experimental data. This, in turn, will improve the AI-based models that are quickly becoming the cornerstone of how rare mutations are assessed clinically.

We’re entering into a new era of understanding in the genetics field that often non-coding regions are as important for disease as coding regions, but the sheer volume of DNA variants to look through is a daunting prospect. Combining precise gene editing techniques with artificial intelligence will allow us to tackle this problem and hopefully shed light on thousands of disease variants that are currently missed because they’re hiding in the dark genome – a major step in developing more precise diagnostics and treatments for a range of diseases.

– Greg Findlay

Greg is one of 478 researchers across Europe to receive one of this year’s Starting Grants. These grants support research across diverse fields, helping researchers at the beginning of their careers to launch their own projects, build research teams and pursue their most promising ideas. 

Ekaterina Zaharieva, European Commissioner for Startups, Research and Innovation, said: “Among the winners in this new round of EU funding are researchers of 51 nationalities. They will be advancing knowledge across a wide range of scientific fields, including cancer, mental health and quantum science. We see leading scientists coming to Europe with these new grants, and many choosing to remain here thanks to this support. This demonstrates Europe’s potential to attract and keep top scientific talent.”