Post-transcriptional regulation in mitochondria. – 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

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.

For more detailed information about our group, visit Rorbach Lab.

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.

Publications

Selected publications

Members and contact

All members of the group

Visiting address

Karolinska Institute, Biomedicum 9D, floor 9, Solnavägen 9, Solna, 171 65, Sweden