Imperial researchers awarded £13.7m to research mitochondrial DNA

A new ARIA-funded consortium led by Imperial aims to crack mitochondrial DNA engineering, opening possibilities for biomedical discovery.

A team led by Dr Nazila Kamaly, Associate Professor in Synthetic Biomaterials and Nanomedicine, has secured funding from the UK’s Advanced Research Innovation Agency (ARIA) to develop technologies that could transform scientists' ability to study and engineer mitochondrial DNA.  

This funding will support PIONEER (Programmable In-Organelle Nucleic-acid Entry, Expression and Retention), a multidisciplinary consortium led by Imperial College London and researchers from the University of Bristol and the University of Glasgow. This project forms part of ARIA’s Precision Mitochondria Programme, bringing together 19 research teams to solve one of the longest-standing challenges in molecular biology.  

Over the last few decades, advances in genetic engineering have enabled scientists to read, write and edit bacterial and nuclear DNA almost routinely, using techniques such as CRISPR. But mitochondria have remained beyond reach as we still cannot reliably deliver new, functional genetic instructions into them, express those instructions and stably maintain them over time.  

Mitochondria are often described as the powerhouses of the cell because they generate the energy needed for cells to function. Uniquely, they have their own DNA material separate from the cell nucleus and locked behind a difficult-to-permeate double membrane. When mitochondria fail to function, however, the effects are profound, causing conditions that are often life-limiting and difficult to treat. Mitochondrial dysfunction has been linked to conditions including neurodegenerative diseases, cancer, metabolic disorders and ageing. 

How PIONEER aims to change this 

The consortium aims to develop an end-to-end capability for mitochondrial genome engineering by creating new methods to deliver synthetic genetic material into mitochondria and ultimately demonstrating successful mitochondrial genome engineering in living systems.  

Dr Kamaly commented: “Every cell in the body depends on mitochondria, yet mitochondrial DNA remains largely untouchable by current genetic medicines. PIONEER exists to close that gap using novel tools, technologies, and biological insight. ARIA's substantial backing gives us the freedom to attempt something this ambitious.” 

The impact could extend beyond one single research area, enabling researchers to better understand how mitochondrial DNA influences cellular function. The technologies developed through PIONEER could help inform future approaches to studying a wide range of diseases and biological processes. 

What makes the project distinctive is its breadth of expertise. Researchers from Imperial, Bristol and Glasgow are combining knowledge from nanomaterials, drug delivery, synthetic biology, artificial intelligence, machine learning, spectroscopy, biophysics and genome engineering to address a challenge that no single discipline could solve alone.  

At Imperial, Dr Kamaly is joined by Professor Oscar Ces, Professor Nick Jones, Professor Kim Jelfs, Professor Maxie Roessler, Dr Becky Greenaway and Dr Alex Ivanov. The wider consortium includes Professor Payam Gamage at the University of Glasgow and Professor Mark Szczelkun at the University of Bristol. 

Dr Kamaly continued: “It is a rare opportunity to work at the intersection of several cutting-edge fields on a problem that will not only bring exciting new fundamental insights but also, if solved, would be a breakthrough for science and humanity.”