Joanna Rorbach Group

Mitochondrial dysfunction is a major contributor to metabolic and neurodegenerative pathologies, ageing and cancer. Indeed, several key factors regulating mitochondrial gene expression are associated with a range of human diseases. The objective of our research is to better understand the post-transcriptional regulatory networks controlling gene expression in mitochondria; as a means to identify pathways and factors impinging upon physiology and disease.

Assistant professor

Joanna Rorbach

Phone: +46-(0)8-524 866 93
Organizational unit: Joanna Rorbach group
E-mail: joanna.rorbach@ki.se

Research Interest

Mammalian mitochondrial ribosomes synthesise a small subset of proteins that are important components of the oxidative phosphorylation machinery, therefore their function is of fundamental importance to cellular metabolism, viability and function.

Most studies of ribosome assembly and function have been carried out on bacterial and eukaryotic cytosolic ribosomes, which differ substantially from mammalian mitoribosomes both compositionally and mechanistically. At present, very little is known about the assembly pathways of mitoribosomes and their regulation. Moreover, many fundamental questions concerning the mechanistic aspects of mitochondrial protein synthesis remain. For example, we do not understand how the nascent protein products of translational machinery are inserted into the inner membrane of mammalian mitochondria.

Our research is directed towards overcoming this knowledge gap, providing a detailed description of mitochondrial ribosome biogenesis, membrane interaction, and structural and biochemical characterisation of different stages of protein synthesis. We employ highly multidisciplinary approaches to address these questions, including ribosome profiling, high-throughput gene targeting, proteomic and cryo-EM methods.

This studies will help us to identify novel factors, some of which may be implicated in disease.  In longer term, a description of these processes will yield valuable insight into how the mitochondrial gene expression is regulated, how and why errors occur, and how this impinges upon cellular function and leads to disease.

Work opportunities

We offer master student, PhD and Postdoc positions to highly motivated and enthusiastic researchers. For details, send an email to joanna.rorbach@ki.se.

Staff

Elham Aryapour Master student
Miriam Cipullo R&D trainee
Anas Khawaja Associated
Sarah Pearce Associated
Joanna Rorbach Assistant professor

Recent publications

Human mitochondrial ribosomes can switch their structural RNA composition.
Rorbach J, Gao F, Powell C, D'Souza A, Lightowlers R, Minczuk M, et al
Proc. Natl. Acad. Sci. U.S.A. 2016 Oct;113(43):12198-12201

Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs.
Gammage P, Gaude E, Van Haute L, Rebelo-Guiomar P, Jackson C, Rorbach J, et al
Nucleic Acids Res. 2016 Sep;44(16):7804-16

Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3.
Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce S, Powell C, et al
Nat Commun 2016 Jun;7():12039

Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries.
Karniely S, Weekes M, Antrobus R, Rorbach J, van Haute L, Umrania Y, et al
MBio 2016 Mar;7(2):e00029

TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies.
Powell C, Kopajtich R, D'Souza A, Rorbach J, Kremer L, Husain R, et al
Am. J. Hum. Genet. 2015 Aug;97(2):319-28

Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy.
Kopajtich R, Nicholls T, Rorbach J, Metodiev M, Freisinger P, Mandel H, et al
Am. J. Hum. Genet. 2014 Dec;95(6):708-20

MRM2 and MRM3 are involved in biogenesis of the large subunit of the mitochondrial ribosome.
Rorbach J, Boesch P, Gammage P, Nicholls T, Pearce S, Patel D, et al
Mol. Biol. Cell 2014 Sep;25(17):2542-55

Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations.
Gammage P, Rorbach J, Vincent A, Rebar E, Minczuk M
EMBO Mol Med 2014 04;6(4):458-66

Polyadenylation in bacteria and organelles.
Rorbach J, Bobrowicz A, Pearce S, Minczuk M
Methods Mol. Biol. 2014 ;1125():211-27

MPV17L2 is required for ribosome assembly in mitochondria.
Dalla Rosa I, Durigon R, Pearce S, Rorbach J, Hirst E, Vidoni S, et al
Nucleic Acids Res. 2014 Jul;42(13):8500-15

ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy.
Haack T, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls T, et al
Am. J. Hum. Genet. 2013 Aug;93(2):211-23

Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease.
Kornblum C, Nicholls T, Haack T, Schöler S, Peeva V, Danhauser K, et al
Nat. Genet. 2013 Feb;45(2):214-9

The post-transcriptional life of mammalian mitochondrial RNA.
Rorbach J, Minczuk M
Biochem. J. 2012 Jun;444(3):357-73