Congratulations to the Luisi and Miska Groups on their award of an ARIA grant in the Precision Mitochondria programme. Pedro Rebelo-Guiomar, Ben Luisi and Payam Gammage (CRUK Scotland Institute) are co-leads on the project ‘Protein-linked nucleic acid design for mitochondrial delivery and expression’, and Damiano Mangoni, Bianca Pierattini and Jon Price from the Miska Group are co-investigators. The ARIA Precision Mitochondria programme is formed of a network of 19 multidisciplinary teams.
Dr Pedro Rebelo-Guiomar said, “We are incredibly grateful to ARIA for supporting our research, and the opportunity to integrate a network of leading researchers and industry partners. This grant will be instrumental in establishing an ambitious research program to pursue emerging frontier topics and open new avenues across fundamental and applied biology.”
Pedro and the team aim to incorporate new genes into mitochondrial DNA and express recombinant proteins from inside the organelle. For delivery, they will attach a piece of nucleic acid to proteins carrying a mitochondrial “address tag”. The resulting nucleic acid–protein adduct will use the organelle’s natural protein-import pathway to move the DNA across both membranes and into the matrix. They will assess which nucleic acid-protein adduct versions are optimal. Alongside this, the team will map – for the first time at scale – the structure and interactions of human mitochondrial RNA, and chart how these shift under drug and genetic perturbation. That map could later train a machine-learning tool to design genetic cargo that mitochondria read efficiently. Together, these lines aim to move mitochondrial genome engineering beyond editing existing sequences towards the stable incorporation and expression of entirely new genetic information.
During the next 5 years, they are expecting new technologies to arise from this programme, primarily aimed at expanding the molecular toolbox for mitochondrial biology. The team’s main goal is to develop methods to deliver nucleic acids into mitochondria and to study the structure of RNAs in this organelle, which has remained a roadblock for mitochondrial research for about 50 years.
Besides creating a strong community of mitochondrial and genome researchers, the work will provide a new way to investigate mitochondrial biology and to test longstanding questions about the role of mitochondria in metabolic, oncological, neurogenerative and other pathologies.