Mitochondrial Genetics
Lead Research Organisation:
MRC Centre Cambridge
Abstract
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. Defects that directly or indirectly affect mitochondrial genes cause human diseases. We are 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. 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.
Technical Summary
Human mitochondria have their own genome (mtDNA) that is two hundred thousand times smaller that the nuclear genome (nDNA) and encodes only thirteen essential subunits of the oxidative phosphorylation (OXPHOS) machinery. Given the relatively small size of the mitochondrial genome our detailed understanding of the molecular mechanism that govern mitochondrial gene maintenance and expression is still surprisingly sketchy. Defects of mtDNA and nDNA are well-recognised cause of genetic disorders that have diverse clinical manifestations ranging from progressive muscle weakness to fatal infantile disease. Much of our understanding of mitochondrial molecular genetics has come from studying rare mitochondrial disorders. Currently there are no effective treatments for these diseases and there are very few animal models for them. The slow progress in gathering more data on how mitochondrial genome is regulated is, in large part, owing to our current inability to edit mtDNA. Genome engineering techniques, analogous to the ones routinely used to modify the nuclear DNA, are not in hand, so we are unable to interrogate the role of cis-acting elements for RNA expression as well as transcription or replication. Furthermore, we are still unable to introduce pathogenic mtDNA mutations at will so their effect could be studied in animal models.
In particular, the programme focuses on:
(i) Studying the basic mechanisms of mitochondrial genome regulation with the main focus on
the novel proteins responsible for nuclolytic processing of precursor mitochondrial RNA, polyadenylation of mitochondrial messenger RNA, post-transcriptional nucleotide modification of mitochondrial RNA and mitoribosome biogenesis.
(ii) The analysis of the key aspects of mitochondrial genome regulation in samples derived from patients affected with mitochondrial disease. This analysis is a source of valuable insights into the pathomechanisms of human disease, and also into basic mitochondrial molecular genetics. Importantly. They provide patients with a molecular diagnosis for prevention (prenatal genetic diagnosis) and counselling.
(iii) Developing new approaches for the genetic modification of mitochondria of living cells.
The key long-term aim is to establish routine methods of genetic modification of mammalian mitochondria. Enzymatic methods are being developed to modify the mitochondrial genome e.g. engineered zinc finger nucleases are delivered to mitochondria in order to deplete cells selectively of specific mtDNA variants.
In particular, the programme focuses on:
(i) Studying the basic mechanisms of mitochondrial genome regulation with the main focus on
the novel proteins responsible for nuclolytic processing of precursor mitochondrial RNA, polyadenylation of mitochondrial messenger RNA, post-transcriptional nucleotide modification of mitochondrial RNA and mitoribosome biogenesis.
(ii) The analysis of the key aspects of mitochondrial genome regulation in samples derived from patients affected with mitochondrial disease. This analysis is a source of valuable insights into the pathomechanisms of human disease, and also into basic mitochondrial molecular genetics. Importantly. They provide patients with a molecular diagnosis for prevention (prenatal genetic diagnosis) and counselling.
(iii) Developing new approaches for the genetic modification of mitochondria of living cells.
The key long-term aim is to establish routine methods of genetic modification of mammalian mitochondria. Enzymatic methods are being developed to modify the mitochondrial genome e.g. engineered zinc finger nucleases are delivered to mitochondria in order to deplete cells selectively of specific mtDNA variants.
Organisations
- MRC Centre Cambridge, United Kingdom (Lead Research Organisation)
- University College London, United Kingdom (Collaboration)
- Max Planck Society (Collaboration)
- Imperial College London, United Kingdom (Collaboration)
- Ludwig Maximilians University Munich (Collaboration)
- University Hospital Bonn (Collaboration)
- Columbia University, United States (Collaboration)
- Newcastle University, United Kingdom (Collaboration)
- Oslo University Hospital (Collaboration)
- Medical Research Council (Collaboration)
- University of Miami, United States (Collaboration)
- South Australian Clinical Genetics Service (Collaboration)
- Harvard University (Collaboration)
- University of Cambridge (Collaboration)
- University of Kent, United Kingdom (Collaboration)
- AstraZeneca plc (Collaboration)
- University of Milan, Italy (Collaboration)
- Helmholtz Zentrum München (Collaboration)
- Radboud University Nijmegen, Netherlands (Collaboration)
- University of Ghent, Belgium (Collaboration)
- Columbia University Medical Center (Collaboration)
- Carlo Besta Neurological Institute (Collaboration)
Publications

Brown A
(2017)
Structures of the human mitochondrial ribosome in native states of assembly.
in Nature structural & molecular biology

Chrzanowska-Lightowlers Z
(2017)
Human mitochondrial ribosomes can switch structural tRNAs - but when and why?
in RNA biology

Coughlin CR
(2015)
Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder.
in Journal of medical genetics

D'Souza AR
(2018)
Mitochondrial transcription and translation: overview.
in Essays in biochemistry

Dalla Rosa I
(2014)
MPV17L2 is required for ribosome assembly in mitochondria.
in Nucleic acids research

Diodato D
(2014)
VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies.
in Human mutation

Feichtinger RG
(2017)
Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies.
in American journal of human genetics

Friederich MW
(2018)
Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.
in Nature communications

Gammage PA
(2016)
Engineered mtZFNs for Manipulation of Human Mitochondrial DNA Heteroplasmy.
in Methods in molecular biology (Clifton, N.J.)

Gammage PA
(2016)
Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs.
in Nucleic acids research
Description | Diagnosis of mitochondrial disease |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
Impact | improvements in clinical service delivery via e.g. pre-natal diagnosis |
Description | Pre-clinical approach to treatment of mtDNA disease |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Citation in clinical reviews |
Description | Biochemical Society General Travel Grant |
Amount | £450 (GBP) |
Organisation | Biochemical Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2017 |
End | 06/2017 |
Description | Boehringer Ingelheim Fonds Travel Grant |
Amount | € 1,060 (EUR) |
Organisation | Boehringer Ingelheim |
Department | Boehringer Ingelheim Fonds |
Sector | Charity/Non Profit |
Country | Germany |
Start | 03/2017 |
End | 04/2017 |
Description | CGAT pump priming proposal |
Amount | £14,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Department | MRC Functional Genomics Unit |
Sector | Academic/University |
Country | United Kingdom |
Start | 03/2012 |
End | 03/2014 |
Description | Clare college - travel grant |
Amount | £300 (GBP) |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 04/2012 |
End | 06/2012 |
Description | EMBO Long Term Fellowship |
Amount | £60,000 (GBP) |
Organisation | European Molecular Biology Organisation |
Sector | Charity/Non Profit |
Country | Germany |
Start | 09/2013 |
End | 10/2015 |
Description | EMBO Short Term fellowship |
Amount | € 7,646 (EUR) |
Funding ID | ASTF 564 - 2015 |
Organisation | European Molecular Biology Organisation |
Sector | Charity/Non Profit |
Country | Germany |
Start | 12/2015 |
End | 02/2016 |
Description | FEBS YTF |
Amount | £500 (GBP) |
Organisation | Federation of European Biochemical Societies (FEBS) |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 04/2012 |
End | 06/2012 |
Description | GAABA |
Amount | € 85,000 (EUR) |
Organisation | Portuguese Foundation for Science and Technology (Portugal) |
Sector | Academic/University |
Country | Portugal |
Start | 08/2015 |
End | 09/2019 |
Description | Homerton College Research Grant |
Amount | £400 (GBP) |
Organisation | University of Cambridge |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2017 |
End | 06/2017 |
Description | Methods for genetic transformation of mitochondria: providing tools for studying mitochondrial myopathies |
Amount | £50,000 (GBP) |
Organisation | French Muscular Dystrophy Association (AFM) |
Sector | Charity/Non Profit |
Country | France |
Start | 03/2010 |
End | 03/2012 |
Description | REMIX ITN |
Amount | € 3,920,000 (EUR) |
Funding ID | 727217 |
Organisation | Marie Sklodowska-Curie Actions |
Sector | Charity/Non Profit |
Country | Global |
Start | 09/2017 |
End | 10/2020 |
Description | The Champ Foundation Grant |
Amount | $100,000 (USD) |
Organisation | The Champ Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 04/2017 |
End | 05/2019 |
Description | Travel fellowship for the MEET Course in Mitochondrial Medicine |
Amount | € 1,000 (EUR) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 12/2014 |
End | 12/2014 |
Title | High-throughput detection of f5C in RNA |
Description | Reduced Bisulfite RNA sequencing (RedBS RNA-Seq) that relies on the chemical reduction of f5C to hm5C by NaBH4, with the resulting hm5C being subsequently detected by RNA BS. The second protocol, 5-formylcytosine Chemically Assisted Bisulfite RNA sequencing (fCAB RNA-Seq) is based upon O-ethylhydroxylamine protection of f5C from bisulfite conversion. [Nat. comm Lindsey Van Haute et al. 2016] |
Type Of Material | Technology assay or reagent |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | These two new, straightforward methods allow base-resolution mapping of f5C in transcriptomes and are expected to facilitate the search for new 5-formylated cytosines, reveal their functional role in both cytoplasmic and mitochondrial RNA therefore assist further expansion of epitranscriptome research. |
Title | In vivo mtDNA manipulation using programmable nucleases |
Description | Over the past decade mitochondrial DNA (mtDNA) has transitioned to broader relevance across diverse fields in biology and medicine. This has largely been thanks to the recognition of mitochondria as a major biochemical hub, the discovery of mitochondrial dysfunction in various diseases and a number of high-profile attempts at preventing hereditary mitochondrial disease using three-parent in vitro fertilisation, or mitochondrial replacement therapy (1-4). Mitochondrial diseases are a genetically diverse group of hereditary, multi-system disorders that are incurable and largely untreatable, with heterogeneous penetrance, presentation and prognosis. The majority of mitochondrial diseases are transmitted through maternally inherited mutations in mtDNA, and patients suffering with these disorders present a substantial disease burden (5). Mitochondrial DNA is a small, circular genome, encoding 13 essential protein subunits of the respiratory chain complexes and ATP synthase. As the mitochondrial genome is multi-copy, with anything from 100-10,000 copies per cell depending on tissue type, mutated mtDNA co-exists with healthy wild-type mtDNA in most patients suffering from mitochondrial disease, a phenomenon known as heteroplasmy. Patient symptoms and outcomes are closely correlated with the extent of mutation load, and approaches to treatment of mtDNA disease by shifting the heteroplasmic ratio in favour of wild-type mtDNA have long been desired and pursued. As mtDNA engineering lags many decades behind its nuclear counterpart, owing to various technical challenges (6) that likely negate the possibility of a functional CRISPR/Cas9 platform in mammalian mitochondria (7), it has not been possible to produce animal models of mtDNA disease until recently. The m.5024C>T tRNAALA strain is the only available mouse model of heteroplasmic mtDNA disease, bearing a pathogenic point mutation that results in biochemical hallmarks of mtDNA disease (diminished steady-state levels of the affected mt-tRNAALA) at high levels of mutant heteroplasmy in cardiac tissue (8). The mouse m.5024C>T mutation is equivalent to the human m.5591G>A mutation in mt-tRNAALA, associated with an adult-onset mitochondrial disease (9). This animal model is also, more broadly, clinically relevant to a large number of mtDNA diseases caused by mutations in mitochondrial tRNAs. In past work from our laboratory, we have engineered a new class of programmable, mitochondria-specific nuclease: the mitochondrially-targeted zinc finger-nuclease (mtZFN), which we have demonstrated can specifically eliminate mutated mtDNA in patient-derived cell models, resulting in recovery of associated cellular dysfunction (10-11). Aspects of this work are protected by the MRC patent on mtZFNs (US9139628 B2). In our recent work we achieved the successful translation of mtZFN technology from in vitro studies to the disease-relevant m.5024C>T tRNAALA mouse model. Through the experiments presented in the manuscript, we demonstrate that: 1) mtZFNs can be engineered to selectively eliminate m.5024C>T mutation with single nucleotide specificity. 2) When delivered systemically by adeno-associated virus (AAV), mtZFNs are capable of robustly manipulating mtDNA heteroplasmy of the targeted tissue. 3) Treatment-induced shifts in mtDNA heteroplasmy are accompanied by recovery of molecular and biochemical phenotypes in cardiac tissue of the m.5024C>T tRNAALA mouse model. 4) We conclude that mtZFNs are an effective tool for the treatment of heteroplasmic mitochondrial disease in mammalian animal models, with potential for development as a new class of therapy. References: [1] Craven L, et al. 2010. Nature. 465: 82-5. [2] Tachibana M, et al. 2013. Nature. 493: 627-31. [3] Hyslop LA, et al. 2016. Nature. 534: 383-6. [4] Kang E, et al. 2016. Nature. 540: 270-275. [5] Gorman GS, et al. 2015. Ann. Neurol. 77: 753-9. [6] Patananan AN, et al. 2016. Cell Metab. 23: 785-96. [7] Gammage PA, et al., 2018. Trends. Genet. in press [8] Kauppila JHK, et al., 2016. Cell Rep. 16: 2980-90. [9] Swalwell H, et al. 2006. Neurology. 66: 447-9. [10] Gammage PA, et al. 2014. EMBO Mol. Med. 6: 458-66. [11] Gammage PA, et al. 2016. Nucleic Acids Res. 44: 7804-16. |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | No |
Impact | Taken together, this study constitute proof-of-principle that a potential cure for all heteroplasmic mitochondrial disease using mtZFNs. We describe possibly universal therapeutic for heteroplasmic mtDNA disease represent a potential transformation in the future prospects of mitochondrial disease, bringing the promise of a cure to an area of medicine that lacks efficacious treatments, let alone curative therapy. Additionally, the existence of viable therapeutics, such as mtZFN, could alter the balance of ethical arguments surrounding the use mitochondrial replacement therapy techniques (1-4), which are controversial and have been licensed partially on the basis of the desperate state of mitochondrial medicine at present. |
URL | http://www.mrc-mbu.cam.ac.uk/projects/2308/genetic-modification-mitochondrial-genome |
Title | MPAT-Seq: Next-generation sequencing-based analysis of RNA polyadenylation |
Description | MPAT-Seq approach allowes to perform the transcriptome-wide parallel assessment of 3' ends of mitochondrial tRNAs. |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | The further application of this technique may be useful to determine the regulation of the 3' end RNA metabolism in other studies |
Title | Quantitative gradient fractionation mass spectrometry (qGFMS) |
Description | This method is based on SILAC proteomics and sucrose density gradient separation of mitoribosomal subunits |
Type Of Material | Technology assay or reagent |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Pending |
Title | Zinc-finger nucleases for manipulation of mtDNA |
Description | We reported an improved version of mitochondrially-targeted engineered zinc-finger nucleases (mtZFNs) designed to eliminate human mtDNA molecules with pathogenic point mutations and large-scale deletions. Expression of mtZFNs successfully led to a reduction in the mutant mtDNA haplotype load, and subsequent repopulation of wildtype mtDNA was found to restore mitochondrial respiratory function in a cybrid cell model. This research was highlighted by: Moraes C. T. (2014) A magic bullet to specifically eliminate mutated mitochondrial genomes from patients' cells. EMBO Mol. Med. 6, 434-435 Gammage, P.A., Rorbach, J., Vincent, A.I., Rebar, E.J, Minczuk, M. (2014) Mitochondrially-targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations. EMBO Mol Med 6, 458-466 |
Type Of Material | Technology assay or reagent |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | Mutations and rearrangements of mitochondrial DNA (mtDNA) are a common cause of human disease, where they often co-exist with wild-type mtDNA within a single cell. Mitochondrially targeted engineered zinc finger nucleases (mtZFNs) can phenotypically rescue a severe mtDNA-mediated dysfunction and show future therapeutic potential. Previously reported mtZFN constructs were redesigned, greatly improving target specificity and allowing their safe use in human mitochondria. The capacity of the novel mtZFN design was validated by selectively degrading point mutant mtDNA associated with neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) and maternally inherited Leigh syndrome (MILS). The use of the novel mtZFNs was expanded by selectively degrading mtDNA harbouring a pathogenic large-scale deletion associated with adult-onset chronic progressive external ophthalmoplegia (CPEO) and, less frequently, Kearns-Sayre syndrome (KSS) and Pearson's marrow pancreas syndrome. Data are provided demonstrating that elimination of deleted, pathogenic mtDNA molecules by mtZFNs is sufficient for full recovery of oxidative phosphorylation in a disease model cell line. |
URL | http://embomolmed.embopress.org/content/6/4/458.long |
Title | mTUNE |
Description | We developed cell model with defined levels of m.8993T>G mutation heteroplasmy, mTUNE, to investigate the metabolic underpinnings of mitochondrial dysfunction |
Type Of Material | Cell line |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | We uncovered a novel link between glycolysis and mitochondrial dysfunction mediated by reductive carboxylation of glutamine. |
Description | Analysis of a novel nuclease in patients presenting combined OXPHOS deficiencies. |
Organisation | Columbia University |
Department | College of Physicians & Surgeons |
Country | United States |
Sector | Academic/University |
PI Contribution | In 2010 we identified a novel mitochondrial deoxyribonuclease. In order to understand its function in human mtDNA maintenance we have studied the phenotypes of gene inactivation by RNAi and overexpression and analysed the biochemical activity of the recombinant enzyme. In 2011 we started a collaboration with five other groups as they had identified a mutation in the coding gene in six individuals from three unrelated families presenting combined OXPHOS deficiency. Currently, we are confirming the phenotypes observed in the RNAi experiments using patient-derived fibroblasts and performing complementation studies. New patients identified in 2016 |
Collaborator Contribution | following the family clinical history and provided clinical data identified mutations |
Impact | The project is multidisciplinary as it involves collaboration between neurologists and molecular biologists. Two papers published: Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Nat Genet. 2013 Feb;45(2):214-9. doi: 10.1038/ng.2501. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, Reyes A, Kornblum C, Sciacco M, Moggio M, Dziembowski A, Kunz WS, Minczuk M. Hum Mol Genet. 2014 Dec 1;23(23):6147-62. doi: 10.1093/hmg/ddu336. We identified a new disease gene which is now routinely screened in patients with mitochondrial disease |
Start Year | 2011 |
Description | Analysis of a novel nuclease in patients presenting combined OXPHOS deficiencies. |
Organisation | Harvard University |
Department | Harvard Medical School |
Country | United States |
Sector | Academic/University |
PI Contribution | In 2010 we identified a novel mitochondrial deoxyribonuclease. In order to understand its function in human mtDNA maintenance we have studied the phenotypes of gene inactivation by RNAi and overexpression and analysed the biochemical activity of the recombinant enzyme. In 2011 we started a collaboration with five other groups as they had identified a mutation in the coding gene in six individuals from three unrelated families presenting combined OXPHOS deficiency. Currently, we are confirming the phenotypes observed in the RNAi experiments using patient-derived fibroblasts and performing complementation studies. New patients identified in 2016 |
Collaborator Contribution | following the family clinical history and provided clinical data identified mutations |
Impact | The project is multidisciplinary as it involves collaboration between neurologists and molecular biologists. Two papers published: Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Nat Genet. 2013 Feb;45(2):214-9. doi: 10.1038/ng.2501. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, Reyes A, Kornblum C, Sciacco M, Moggio M, Dziembowski A, Kunz WS, Minczuk M. Hum Mol Genet. 2014 Dec 1;23(23):6147-62. doi: 10.1093/hmg/ddu336. We identified a new disease gene which is now routinely screened in patients with mitochondrial disease |
Start Year | 2011 |
Description | Analysis of a novel nuclease in patients presenting combined OXPHOS deficiencies. |
Organisation | Ludwig Maximilian University of Munich (LMU Munich) |
Department | Department of Human Genetics |
Country | Germany |
Sector | Academic/University |
PI Contribution | In 2010 we identified a novel mitochondrial deoxyribonuclease. In order to understand its function in human mtDNA maintenance we have studied the phenotypes of gene inactivation by RNAi and overexpression and analysed the biochemical activity of the recombinant enzyme. In 2011 we started a collaboration with five other groups as they had identified a mutation in the coding gene in six individuals from three unrelated families presenting combined OXPHOS deficiency. Currently, we are confirming the phenotypes observed in the RNAi experiments using patient-derived fibroblasts and performing complementation studies. New patients identified in 2016 |
Collaborator Contribution | following the family clinical history and provided clinical data identified mutations |
Impact | The project is multidisciplinary as it involves collaboration between neurologists and molecular biologists. Two papers published: Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Nat Genet. 2013 Feb;45(2):214-9. doi: 10.1038/ng.2501. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, Reyes A, Kornblum C, Sciacco M, Moggio M, Dziembowski A, Kunz WS, Minczuk M. Hum Mol Genet. 2014 Dec 1;23(23):6147-62. doi: 10.1093/hmg/ddu336. We identified a new disease gene which is now routinely screened in patients with mitochondrial disease |
Start Year | 2011 |
Description | Analysis of a novel nuclease in patients presenting combined OXPHOS deficiencies. |
Organisation | Oslo University Hospital |
Department | Department of Medical Genetics |
Country | Norway |
Sector | Hospitals |
PI Contribution | In 2010 we identified a novel mitochondrial deoxyribonuclease. In order to understand its function in human mtDNA maintenance we have studied the phenotypes of gene inactivation by RNAi and overexpression and analysed the biochemical activity of the recombinant enzyme. In 2011 we started a collaboration with five other groups as they had identified a mutation in the coding gene in six individuals from three unrelated families presenting combined OXPHOS deficiency. Currently, we are confirming the phenotypes observed in the RNAi experiments using patient-derived fibroblasts and performing complementation studies. New patients identified in 2016 |
Collaborator Contribution | following the family clinical history and provided clinical data identified mutations |
Impact | The project is multidisciplinary as it involves collaboration between neurologists and molecular biologists. Two papers published: Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Nat Genet. 2013 Feb;45(2):214-9. doi: 10.1038/ng.2501. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, Reyes A, Kornblum C, Sciacco M, Moggio M, Dziembowski A, Kunz WS, Minczuk M. Hum Mol Genet. 2014 Dec 1;23(23):6147-62. doi: 10.1093/hmg/ddu336. We identified a new disease gene which is now routinely screened in patients with mitochondrial disease |
Start Year | 2011 |
Description | Analysis of a novel nuclease in patients presenting combined OXPHOS deficiencies. |
Organisation | University Hospital Bonn |
Department | Department of Epileptology |
Country | Germany |
Sector | Academic/University |
PI Contribution | In 2010 we identified a novel mitochondrial deoxyribonuclease. In order to understand its function in human mtDNA maintenance we have studied the phenotypes of gene inactivation by RNAi and overexpression and analysed the biochemical activity of the recombinant enzyme. In 2011 we started a collaboration with five other groups as they had identified a mutation in the coding gene in six individuals from three unrelated families presenting combined OXPHOS deficiency. Currently, we are confirming the phenotypes observed in the RNAi experiments using patient-derived fibroblasts and performing complementation studies. New patients identified in 2016 |
Collaborator Contribution | following the family clinical history and provided clinical data identified mutations |
Impact | The project is multidisciplinary as it involves collaboration between neurologists and molecular biologists. Two papers published: Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Nat Genet. 2013 Feb;45(2):214-9. doi: 10.1038/ng.2501. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, Reyes A, Kornblum C, Sciacco M, Moggio M, Dziembowski A, Kunz WS, Minczuk M. Hum Mol Genet. 2014 Dec 1;23(23):6147-62. doi: 10.1093/hmg/ddu336. We identified a new disease gene which is now routinely screened in patients with mitochondrial disease |
Start Year | 2011 |
Description | Analysis of a novel nuclease in patients presenting combined OXPHOS deficiencies. |
Organisation | University of Milan |
Department | Department of Neurology |
Country | Italy |
Sector | Academic/University |
PI Contribution | In 2010 we identified a novel mitochondrial deoxyribonuclease. In order to understand its function in human mtDNA maintenance we have studied the phenotypes of gene inactivation by RNAi and overexpression and analysed the biochemical activity of the recombinant enzyme. In 2011 we started a collaboration with five other groups as they had identified a mutation in the coding gene in six individuals from three unrelated families presenting combined OXPHOS deficiency. Currently, we are confirming the phenotypes observed in the RNAi experiments using patient-derived fibroblasts and performing complementation studies. New patients identified in 2016 |
Collaborator Contribution | following the family clinical history and provided clinical data identified mutations |
Impact | The project is multidisciplinary as it involves collaboration between neurologists and molecular biologists. Two papers published: Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. Kornblum C, Nicholls TJ, Haack TB, Schöler S, Peeva V, Danhauser K, Hallmann K, Zsurka G, Rorbach J, Iuso A, Wieland T, Sciacco M, Ronchi D, Comi GP, Moggio M, Quinzii CM, DiMauro S, Calvo SE, Mootha VK, Klopstock T, Strom TM, Meitinger T, Minczuk M, Kunz WS, Prokisch H. Nat Genet. 2013 Feb;45(2):214-9. doi: 10.1038/ng.2501. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, Reyes A, Kornblum C, Sciacco M, Moggio M, Dziembowski A, Kunz WS, Minczuk M. Hum Mol Genet. 2014 Dec 1;23(23):6147-62. doi: 10.1093/hmg/ddu336. We identified a new disease gene which is now routinely screened in patients with mitochondrial disease |
Start Year | 2011 |
Description | Analysis of protein localisation depending on mtDNA content |
Organisation | University of Kent |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Providing inducible human cell line for allowing for controlled reduction of the copy number of mitochondrial DNA |
Collaborator Contribution | Analysis of protein localisation in conditions of reduced mtDNA copy number |
Impact | Unknown |
Start Year | 2012 |
Description | Designing mitochondrial zinc finger nucleases |
Organisation | Imperial College London |
Department | Imperial College Trust |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Developing mitochondrially-targeted engineered nucleases to eliminate human mtDNA molecules with pathogenic point mutations and large-scale deletions |
Collaborator Contribution | Assembling and validating zinc finger proteins |
Impact | It is anew partnership - no outcomes yet |
Start Year | 2020 |
Description | Manipulating mtDNA heteroplasmy in vivo using engineered nucleases |
Organisation | Max Planck Society |
Department | Max Planck Institute for the Biology of Ageing |
Country | Germany |
Sector | Academic/University |
PI Contribution | We have generated a mtZFN library specific to mtDNA mutation present in a model strain, tested them in mouse embryonic fibroblasts (MEF) from the mt-tRNAAla mouse line and identified constructs capable of effective reduction of mutant load. We will deliver these ZFNs affected mice with optimal mtZFN constructs by organtropic, recombinant adeno-associated viruses (AAVs). We will also manipulte mtDNA heteroplasmy in germline using mtZFN and mitoTALENs (the latter obtained in collaboration with Uni of Miami) |
Collaborator Contribution | Providing mouse model, help and expertise in mtZFN research that may led to generation of pre-clinical data useful for a development of an effective treatment of mtDNA disease in the future. |
Impact | pending, likely to be societal. Some protocols for generation of mtZFN published: Gammage PA, Van Haute L, Minczuk M. Engineered mtZFNs for Manipulation of Human Mitochondrial DNA Heteroplasmy. Methods Mol Biol. 2016;1351:145-62. doi: 10.1007/978-1-4939-3040-1_11 Vectors available at Addgen |
Start Year | 2017 |
Description | Manipulating mtDNA heteroplasmy in vivo using engineered nucleases |
Organisation | University of Miami |
Country | United States |
Sector | Academic/University |
PI Contribution | We have generated a mtZFN library specific to mtDNA mutation present in a model strain, tested them in mouse embryonic fibroblasts (MEF) from the mt-tRNAAla mouse line and identified constructs capable of effective reduction of mutant load. We will deliver these ZFNs affected mice with optimal mtZFN constructs by organtropic, recombinant adeno-associated viruses (AAVs). We will also manipulte mtDNA heteroplasmy in germline using mtZFN and mitoTALENs (the latter obtained in collaboration with Uni of Miami) |
Collaborator Contribution | Providing mouse model, help and expertise in mtZFN research that may led to generation of pre-clinical data useful for a development of an effective treatment of mtDNA disease in the future. |
Impact | pending, likely to be societal. Some protocols for generation of mtZFN published: Gammage PA, Van Haute L, Minczuk M. Engineered mtZFNs for Manipulation of Human Mitochondrial DNA Heteroplasmy. Methods Mol Biol. 2016;1351:145-62. doi: 10.1007/978-1-4939-3040-1_11 Vectors available at Addgen |
Start Year | 2017 |
Description | Mitochondria in drug toxicity |
Organisation | AstraZeneca |
Department | Research and Development AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | Hosting and training a collaborative post-doc |
Collaborator Contribution | Providing access to a high-throughput measurements of mitochondrial function. |
Impact | ongoing |
Start Year | 2014 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | Carlo Besta Neurological Institute |
Country | Italy |
Sector | Public |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | Columbia University Medical Center |
Country | United States |
Sector | Academic/University |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | Helmholtz Zentrum München |
Department | Institute of Human Genetics |
Country | Germany |
Sector | Academic/University |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | Newcastle University |
Department | School of Biomedical Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | Radboud University Nijmegen |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | South Australian Clinical Genetics Service |
Country | Australia |
Sector | Hospitals |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | University College London |
Department | Faculty of Medical Sciences |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | Mitochondrial RNA metabolism and human disease |
Organisation | University of Ghent |
Country | Belgium |
Sector | Academic/University |
PI Contribution | We analyse molecular phenotypes associated with mutations in muclaer genes involved in mitochondrial RNA processing and post-transcriptional modification. |
Collaborator Contribution | Identification of mutations by next-generation exome sequencing in patients with combined OXPHOS defects |
Impact | Several papers e.g: Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, Rorbach J, Lantaff R, Blanco S, Sauer S, Kotzaeridou U, Hoffmann GF, Memari Y, Kolb-Kokocinski A, Durbin R, Mayr JA, Frye M, Prokisch H, Minczuk M.Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016 Jun 30;7:12039. doi: 10.1038/ncomms12039. Haack, T.B.*, Kopajtich, R.*, Freisinger, P.*, Wieland, T., Rorbach, J, Nicholls, T.J., Enrico Baruffini, E., Walther, A., Danhauser, K., Zimmermann, F.A., Husain, R.A., Schum, J., Mundy, H., Ferrero, I., Strom, T.M., Meitinger, T., Taylor, R.W., Minczuk, M**., Mayr, J.A., Prokisch, H.** (2013) ELAC2 Mutations Cause a Mitochondrial RNA Processing Defect Associated with Hypertrophic Cardiomyopathy. Am J Hum Genet 93, 211-223 Kopajtich, R.,* Nicholls, T.J.,* Rorbach, J.,* Freisinger, P., Mandel, H., Vanlander, A., Ghezzi, D., Carrozzo, R., Taylor, R.W., Marquard, K., Murayama, K., Wieland, T., Schwarzmayr, T., Mayr, J.A., Pearce, S. F., Powell, C. Saada, A., Ohtake, A., Invernizzi, F., Lamantea, E., Sommerville, E. W., Pyle, A., Chinnery, P. F., Crushell, E., Okazaki, Y., Kohda, M., Kishita, Y., Tokuzawa, Y., Smet, J., Régal, L., Lorber, A., Khoury, A., Zeviani, M., Strom, T. M., Meitinger, T., Bertini, E. S., Van Coster, R., Klopstock, T., Haack, T. B., Minczuk, M.,** Prokisch, H.** (-) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy Am J Hum Genet 95, 708-20 Vanlander, A.V., Menten, B., Smet, J., De Meirleir, L., Sante, T., De Paepe, B., Seneca, S., Pearce, S.F., Powell, C.A., Vergult, S., Michotte, A., De Latter, E., Vantomme, L., Minczuk, M. and Van Coster, R. (-) Two siblings with homozygous pathogenic splice site mutation in mitochondrial asparaginyl-tRNA synthetase (NARS2) Hum. Mutat Mutat 36, 222-231 Powell, C.A.*, Kopajtich, R.*, D'Souza, A.R., Rorbach, J., Dallabona, C., Donnini, C., Alston, C.L., Griffin, H., Pyle, A., Chinnery, P.F., Strom, T.M., Meitinger, T., Rodenburg, R.J., Schottmann, G., Schuelke, M., Romain, N., Haller, R., Ferrero, I., Haack, T.B., Taylor, R.W., Prokisch, H.**, Minczuk, M. (2015) Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory-chain deficiencies. Am J Hum Genet. 97,319-328 Coughlin, C.R. Scharer, G.H., Friederich, M.W., Yu, H.C., Geiger, E.A., Creadon-Swindell, G., Collins, A.E., Vanlander, A.V., Coster, R.V., Powell, C.A., Swanson, M.A., Minczuk, M., Van Hove, J.L., Shaikh, T.H. (2015) Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. J Med Genet. 52,532-540 and more |
Start Year | 2011 |
Description | RNA polyadenylation in the maintenance and expression of the mitochondrial genome |
Organisation | Medical Research Council (MRC) |
Department | MRC Functional Genomics Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Establishing how poly(A) tails regulate mt-RNA abundance and mitochondrial protein synthesis Identifying novel proteins that play a role in mitochondrial poly(A) tail metabolism Determining whether poly(U) extensions play a role in RNA surveillance and/or turnover in human mitochondria |
Collaborator Contribution | Next-generation sequencing and analysis of mitochondrial RNA |
Impact | finantial support |
Start Year | 2012 |
Description | Role of mitochondria in HCMV infection |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided analysis of mitochondrial function in cellular model of HCMV infection |
Collaborator Contribution | Provided HCMV infection model and discovered the link between varial infection and mitochondrial gene expression |
Impact | publication: Karniely S, Weekes MP, Antrobus R, Rorbach J, Van Haute L, Umrania Y, Smith DL, Stanton RJ, Minczuk M, Lehner P, Sinclair JH (2016) Human cytomegalovirus infection upregulates the mitochondrial transcription and translation machineries. |
Start Year | 2015 |
Title | POLYPEPTIDE TARGETING TO MITOCHONDRIA |
Description | Methods for delivering non-mitochondrial proteins to mitochondria are provided. Also provided are nucleic acid constructs comprising a coding sequence encoding a DNA- binding polypeptide, fused to a mitochondrial targeting sequence (MTS) and a nuclear export signal (NES), and the encoded proteins. The construct successfully delivers DNA binding proteins to the mitochondrion. A chimeric methylase based on the above construct is successfully delivered to mitochondria, resulting in modification of |
IP Reference | EP1974034 |
Protection | Patent granted |
Year Protection Granted | 2008 |
Licensed | No |
Impact | nil |
Description | "Work in Progress" talk to the Selwyn College MCR Society |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | A graduate student was invited to give an overview of her studies and her life as a graduate student of the University of Cambridge/MRC MBU. . |
Year(s) Of Engagement Activity | 2013 |
Description | Biglands Green School visit - Cambridge Outreach event |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | a short talk about general biology was given, folowed by a discusion about science ith an aim to getting them interested in the sciences, and with a hope of inspiring applications to Cambridge in the future. not measurable yet |
Year(s) Of Engagement Activity | 2010 |
Description | Cambridge Science Festival |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Type Of Presentation | Poster Presentation |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Presentations of posters, explanations of mitochondrial processes, movies, interaction with members of the public. Interest in the Unit's open day. |
Year(s) Of Engagement Activity | 2013 |
Description | Cambridge University Widening Participation Programme |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | PhD student (Payam Gammage) gave a talk to 25 FE college students (doing their A levels) on life as a graduate student at Cambridge and science the MBU. Venue: St. John's College, Cambridge. Interaction from interested A level students. |
Year(s) Of Engagement Activity |
Description | Clare College - Gillespie Conferencing Centre |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | To give advice and share experiences of undergraduate and graduate study with a group of aspiring 17-18 year old biologists (largely Oxbridge applicants) from a deprived area of East London. not measurable yet |
Year(s) Of Engagement Activity | 2011 |
Description | Clare College STEM Outreach Lecture Series |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Undergraduate students |
Results and Impact | A graduate student participated in a series of lectures aimed at undergraduates/summer students of the University of Cambridge Greater awareness of the Unit's activities. |
Year(s) Of Engagement Activity | 2013 |
Description | Dissemination of scientific achievements via the internet |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Dissemination of scientific achievements and publications to the general public, scientists and others via the Unit's website, Twitter and Facebook. https:/www.facebook.com/mrc-mbu Twitter - @MRC_MBU https://www.mrc-mbu.cam.ac.uk https://www.mrc-mbu.cam.ac.uk/research-groups/minczuk-group |
Year(s) Of Engagement Activity | 2017,2018,2019,2020,2021,2022 |
URL | https://www.mrc-mbu.cam.ac.uk/research-groups/minczuk-group |
Description | Dissemination of scientific achievements via the internet |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Dissemination of scientific achievements and publications to the general public, scientists and others via the Unit's website, Twitter and Facebook. https:/www.facebook.com/mrc-mbu Twitter - @MRC_MBU http://www.mrc-mbu.cam.ac.uk http://www.mrc-mbu.cam.ac.uk/people/michal-minczuk |
Year(s) Of Engagement Activity | 2015,2016,2017,2018,2019,2020,2021 |
URL | http://www.mrc-mbu.cam.ac.uk/people/michal-minczuk |
Description | Graduate Research Forum |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | talko on general themes in mitochondrial research, the importance of understanding mitochondrial processes (as a key factor in the pathogenesis of many diseases and also in general health/ageing), and on research in our group. not measurable yet |
Year(s) Of Engagement Activity | 2011 |
Description | Lecture at Clare College Outreach summer school |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | A graduate student gave a lecture on University/MRC life at the Clare College Outreach summer school. Increased awareness amongst students considering University courses. |
Year(s) Of Engagement Activity | 2013 |
Description | MRC MBU Annual Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Overview of work at the MRC MBU; explanations of how mitochondrial dysfunction causes mitochondrial diseases. Audience: Secondary school students, tutors, general public and scientists from neighbouring institutes. Impact: increased awareness. |
Year(s) Of Engagement Activity | 2015,2016 |
URL | http://www.mrc-mbu.cam.ac.uk/news/2335/open-day-2015 |
Description | Mayfield Primary School, Cambridge |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Members of the MBU visited Mayfield Primary School, Cambridge to participate in their Science Day. This was a classroom based event, with students in Reception (aged 4 and 5 years) rotating around the room. After a short talk, the children interacted with Lego models, pipetting and colouring. |
Year(s) Of Engagement Activity | 2017 |
Description | Opportunities Ahead |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | The event is aimed at school students in years 5 & 6 in the morning followed by students from secondary schools, sixth-forms, recent school and college leavers and parents in the afternoon. The idea is to showcase the wide variety of companies in the Cambridge area and get young people excited about their future. Signpost 2 Skills is a new service designed to guide students from education and into working life by bringing employers into schools and students into businesses. It is funded by the Greater Cambridge Greater Peterborough LEP and the Greater Cambridge City Deal, and delivered by social enterprise, Form the Future. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.mrc-mbu.cam.ac.uk/news/2768/opportunities-ahead-careers-fair-cambridge |
Description | Padova, Italy |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Undergraduate students |
Results and Impact | Mitochondrial Biology and Genetics Lecture Series: joint initiative between the Galilean School of Higher Education and PhD Courses in Biosciences and Biomedical Sciences of the University of Padova. |
Year(s) Of Engagement Activity | 2015 |
Description | Presentations during the MRC Centenary Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Members of the public attended the Unit's open day to celebrate the MRC's Centenary. Increased awareness and interest. |
Year(s) Of Engagement Activity | 2013 |
Description | Provision of images for use by the Champ Foundation |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Provision of images for use by the Champ Foundation for a social media campaign. |
Year(s) Of Engagement Activity | 2021 |
Description | Public Engagement Training |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | A Public Engagement Workshop entitled, "Who are the public and what do they think?" Aimed at: Understanding body language Intentions and measuring success Engagement in practice - case studies/experiences Places to find further support and methods to engage further |
Year(s) Of Engagement Activity | 2017 |
Description | Queen Edith's Primary School, Cambridge |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Members of the MBU visited Queen Edith's Primary School, Cambridge to participate in their Science Day. This was a carousel-type event, with students in years 1-4 rotating around the room. The demonstrations included Lego models, computer games, pipetting and DNA sequencing puzzles. Feedback: Thank you so much for coming here today. The children have not stopped talking about it since leaving the room. |
Year(s) Of Engagement Activity | 2017 |
Description | SET for BRITAIN |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Exhibition of posters by early-career research scientists, engineers and mathematicians. By competition. MBU participant: Sarah Pearce. SET for BRITAIN exists to raise the profile of Britain's early-stage researchers at Westminster by engaging Members of both Houses of Parliament with current science, engineering and mathematics research being undertaken in the UK, especially that by their local constituents and in their local University. Few of them have science or technology degrees, but around 100 Parliamentarians usually attend during the day. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.setforbritain.org.uk/2016event.asp |
Description | The Norwood School |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Visit to the lab by three year 13 students along with their teacher to discuss the concepts and practicalities of gel electrophoresis, gene technology, and gene manipulation. Impact: increased awareness |
Year(s) Of Engagement Activity | 2015 |
Description | University Press release about published research with potential for gene editing to tackle mitochondrial disorders |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Defective mitochondria - the 'batteries' that power the cells of our bodies - could in future be repaired using gene-editing techniques. Research led by Michal Minczuk and published in Nat Comms has shown that it is possible to modify the mitochondrial genome in live mice, paving the way for new treatments for incurable mitochondrial disorders. Silva-Pinheiro, S et al. In vivo mitochondrial base editing via adenoassociated viral delivery to mouse post-mitotic tissue. Nature Comms; 8 Feb 2022; DOI: 10.1038/s41467-022-28358-w |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.cam.ac.uk/research/news/study-in-mice-shows-potential-for-gene-editing-to-tackle-mitocho... |
Description | Visit of Japanese medical students |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Visit to Michal Minczuk's laboratory by Japanese medical students. Four members of the research group participated, giving an insight into the work of the Unit, the laboratory and answering questions from the students. Impact - increased awareness. |
Year(s) Of Engagement Activity | 2015 |
Description | Woodhouse College Visit (to MBU) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Eight year 12 students from Woodhouse College visited on Wednesday, 28th of June for a day focused on gene manipulation. It began with discussions surrounding the ethics and practicalities of genetic engineering followed by a practical on CRISPR-Cas9, PCR, and gel electrophoresis. This was concluded with a session to interpret the results obtained and to discuss their significance. Feedback: It was my first experience in a lab based environment and greatly broadened my perspective of the opportunities available in a career of science.It was an amazing trip, really interesting to see a research scientist's day to day life. In addition participating in a PCR and gel electrophoresis was fascinating and I received advice to help me for my university application. Thanks.The experience we got in the lab was invaluable and the techniques we used were not only relevant to our curriculum but really enjoyable. We got to explore and be a part of a really exciting, cutting-edge development in biomedical science , CRISPR- Cas9! The trip provided an incredible motivation to succeed and aim high. I am incredibly thankful for the opportunity.Visiting a working lab was an exciting opportunity and gave me a great understanding of the techniques biochemists use, including CRISPR/Cas9 which I had heard about in the media, but being so cutting edge I was surprised that the technique was so commonplace in the lab. A similar visit took place in 2019. |
Year(s) Of Engagement Activity | 2017,2018,2019 |
Description | Work Experience |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Visit by three Year 10 students (age 15) to the Unit for a week each - work experience/shadowing in various research groups/environments, chaperoned throughout by individual members of the Unit. Presentation by the visitors at the end of their week. |
Year(s) Of Engagement Activity | 2016,2017 |