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World first Generative and Synthetic Genomics Programme launched at Wellcome Sanger Institute

A world-first new programme has been launched at the Wellcome Sanger Institute, focused on generative and synthetic genomics.

It becomes the sixth programme of research at the institute and will bring together computational and experimental scientists to understand and predict the effects of editing each and every one of the building blocks of DNA, and engineer biological systems.

Prof Matt Hurles, director of the Wellcome Sanger Institute. Picture: Onur Pinar / Wellcome Sanger Institute
Prof Matt Hurles, director of the Wellcome Sanger Institute. Picture: Onur Pinar / Wellcome Sanger Institute

Genomic data on a huge scale will be generated and computational models designed using machine learning and artificial intelligence (AI) to make predictions in molecular biology, such as working out the impact of mutations on disease.

Researchers will also develop the technologies to write and edit genomes at scale and speed, laying the foundations for a new era of predictive and programmable molecular biology, and the routine synthesis and engineering of genomes.

Supported by additional funding from Wellcome, the programme is expected to have a transformative impact on medicine, agriculture and biotechnology.

Prof Ben Lehner, head of generative and synthetic genomics at the institute, said he was “incredibly excited” by the launch

“Biology has accelerated to a point where a PhD student today can perform more experiments on genes and proteins than the entire global research effort could a decade ago,” he said. “Plus, we can develop highly predictive models that use artificial intelligence. It will be the combination of these technologies that will enable us to solve the fundamental question of how genetic sequence determines the properties and regulation of proteins.

“To do this we require huge amounts of data, and the Sanger Institute’s capabilities of large-scale data generation and genomics expertise make it the natural place for us to undertake this ambitious research.

“We believe that the transformation of biology into a programmable engineering science will be the most important technological revolution of this century, and that generative and synthetic genomics will open up unprecedented possibilities for industry, agriculture, the environment, and medicine.”

Despite the advances made using genomics and molecular biology, scientists still struggle to predict how biological systems respond to mutations and engineering biology remains difficult. The Sanger Institute says that is because a fundamental question - how DNA sequences determine the properties and regulation of proteins and RNAs - remains practically unsolved.

But with advances in DNA sequencing, synthesis and editing technologies now enabling millions of experiments to be performed in parallel, and the revolution in machine learning and AI, highly predictive and generative models can now be developed for complex tasks.

By predicting the effects of individual and combinations of mutations on functional biology, researchers can design the properties, activities, regulation and expression of proteins and RNAs from scratch.

The goal of the Generative and Synthetic Genomics Programme is not only accurate prediction and engineering, but understanding the mechanics of how this works.

Prof Matthew Hurles, director of the institute, said: “As the Sanger Institute enters its 30th year, we are launching a tremendously exciting endeavour to bring together computational and experimental research groups to form the world’s first programme for Generative and Synthetic Genomics. We aim to attract talent from across the globe and build teams with diverse expertise to solve fundamental questions in biology.”

He said the field has “huge translational potential” and could “propel a quantum leap in our ability to use genomic information in medical care”.

And he added: “This new programme will also train and inspire a new generation of life science innovators and entrepreneurs to build new companies to take forward, in a responsible manner, the boundless possibilities afforded by new capabilities in engineering biology.”

The programme’s initial focus will be the protein machines that build our bodies and how they are controlled to make it much easier to engineer proteins as therapeutics and for clean biotechnology. This will lay the foundations for the longer-term vision of generating models for engineering gene pathways, and entire cells and tissues for medical and biotechnological applications.

That means the team wants to understand, predict and engineer the effects of editing every nucleotide – the building blocks of DNA – in every genome.

Then, they will develop the technologies to write and edit genomes at scale and speed, making it easier for scientists to understand how the genomes work and allow them to engineer responsibly the genomes of simpler organisms such as yeast and bacteria as non-polluting factories to make useful products. A policy team is already working on the ethical implications of creating synthetic genomes.

Such work could accelerate the development of therapeutics, underpin the engineering of clean biological solutions to replace polluting industry, and facilitate the rapid engineering of cells which could help adapt agriculture to our changing climate.

Michael Dunn, director of discovery research at Wellcome, said: “We have made huge progress on research into proteins, genes, and the science of life itself. Yet we still know so little about how our genetics and variations in our DNA shape our fundamental biological systems. However, with the unprecedented acceleration of new technologies such as machine learning and AI, we are at an exciting crossroads, with the ambitious task of predicting – and even engineering – gene function now a genuine reality.

“We are delighted to support the Wellcome Sanger Institute’s bold Generative and Synthetic Genomics Programme. Harnessing these new technologies and integrating them with world-leading genomics research matches Wellcome’s vision for discovery research, taking on the big questions that will advance our understanding of life, health, and wellbeing.”

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