Michal Minczuk
MRC Investigator
Mitochondrial genetics: Mitochondrial genome engineering to unravel the genetic links between mitochondrial gene regulation and human disease for future therapies
In eukaryotic organisms almost all genetic information is encoded in DNA present in the nucleus of the cell, but a small DNA molecule inhabits mitochondria, cellular structures that provide energy from food for the cells to use. Mitochondrial DNA contains genes that are vital for the physiological functioning of the cell, and genetic defects causing dysfunction of mitochondrial DNA can lead to human diseases. We still do not know how mitochondrial genes work exactly.One of the ways to investigate the role of a gene, or to discover its biological function, it to change or disrupt DNA, and then to look for the effect on cultured cells, or on the whole organism. These methods of genetic modification are often powerful ways of studying disease genes encoded in the nucleus, but they cannot be applied to mammalian mitochondrial DNA. Also, many genes regulating mitochondrial function are still unknown. Therefore, our research goals are to identify new genes regulating mitochondria, define how these mitochondrial genes operate and to provide the technology to allow mammalian mitochondrial DNA to be modified genetically. It could be an invaluable way of understanding mitochondrial diseases and for advancing the quest for therapies.
Biography
Michal obtained a Master’s degree in Biotechnology (1999) and PhD in Biological Sciences (2003) from the University of Warsaw, Poland, carrying out research in the Institute of Genetics and Biotechnology. From 2004–2007 he was an FEBS Postdoctoral Fellow in the group of Aaron Klug at Medical Research Council (MRC), Laboratory of Molecular Biology, Cambridge. Michal joined the MRC Mitochondrial Biology Unit as an Investigator Scientist (2007) and in 2009 he became a MRC Investigator. Throughout his career Michal has received numerous awards and personal fellowships, including the Prime Minister Prize for his PhD thesis, Award of the Foundation for Polish Science, EMBO and FEBS Fellowships, served as an editor of several journals and books and organised a number of scientific conferences. More recently, Michal has co-founded Pretzel Therapeutics, a start-up biotechnology company that focuses on the development of therapies to treat unmet needs in diseases driven by mitochondrial dysfunction.
Publications
Selected Publications
(2022)
A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit.
Nat Commun. 13:929
Silva-Pinheiro P, Nash PA, Van Haute L, Mutti CD, Turner K & Minczuk M (2022)
In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue.
Nat Commun. 13, 750
Silva-Pinheiro P & Minczuk M (2021)
The potential of mitochondrial genome engineering
Nat Rev Genet, doi: 10.1038/s41576-021-00432-x
Elongational stalling activates mitoribosome-associated quality control.
Science 370, 1105 - 1110
Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.
Nat Med 24, 1691-1695
Maturation of selected human mitochondrial tRNAs requires deadenylation.
eLife 6, e27596
Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3.
Nat Commun 7, 12039
TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.
Am J Hum Genet 97, 319-28