Dr Johannes Spelbrink
From a young age I have had a keen interest in science. After a 3-month laboratory rotation during my Master’s in molecular biology, I was sold and became a true ‘mitochondriac’. My PhD in mitochondrial subject paved the path for a lifelong career in mitochondrial biology.
Dr Hans Spelbrink is a senior researcher at the Radboudumc, Department of paediatrics & the Radboud Center for Mitochondrial Medicine, Nijmegen, Netherlands.
Dr Hans Spelbrink, who in the past has worked mostly on mtDNA maintenance, has in recent years expanded his interests towards studying mitochondrial gene expression in a broader sense, also in light of the ever-increasing number of disease genes identified in this process and the many levels of the interplay between mtDNA and mtRNA metabolism. In a recent publication, he has shown that two classical mtDNA replication factors, the mtDNA helicase Twinkle and the single-stranded DNA-binding protein, have additional functions in RNA granules and RNA turnover, in addition suggesting that RNA granules are perhaps first and foremost involved in dealing with mitochondrial long non-coding RNAs. Nonetheless, the roles that RNA granules play in mitochondrial gene expression are still far from clear and this has sparked his interest in also developing novel methods to study mitochondrial RNA metabolism.
The Spelbrink laboratory is affiliated with the department of paediatrics and embedded in the Nijmegen Center for Mitochondrial Medicine. Within this centre, most basic research is focused on mitochondrial structure and function in relation to mitochondrial OXPHOS disorders. These form one of the largest groups of metabolic disorders with a birth prevalence of at least 1 in 5000.
- Piro-Mégy C. et al. (2020), Dominant mutations in mtDNA maintenance gene SSBP1 cause optic atrophy and foveopathy. J Clin Invest. 2020;130(1):143–156. Spelbrink J. is co-author. DOI
- Hensen F. et al. (2019), Mitochondrial RNA granules are critically dependent on mtDNA replication factors Twinkle and mtSSB. Nucleic Acids Research, Volume 47, Issue 7, Pages 3680–3698. Spelbrink J. is co-author. DOI
- van Esveld S.L. et al. (2019), A Combined Mass Spectrometry and Data Integration Approach to Predict the Mitochondrial Poly(A) RNA Interacting Proteome. Front. Cell Dev. Biol. Spelbrink J. and Huynen M.A. are co-authors. DOI
- Cluett T.J. et al. (2018), Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication. Nucleic Acids Research, Volume 46, Issue 20, Pages 10771–10781. Spelbrink J. is co-author. DOI
- Holt I.J., Spinazzola A., Janssen M. and Spelbrink J. (2022). In: Physician’s Guide to the Diagnosis, Treatment, and Follow-up of Inherited Metabolic Diseases. Chapter 45: Disorders of Replication, Transcription and Translation of Mitochondrial DNA. ISBN 978-3-030-67726-8.
After obtaining an MSc in biology at the University of Amsterdam (UvA), Dr. Spelbrink enrolled as a PhD student in the laboratory of the late Dr. Coby van den Bogert at the Academic Medical Centre (UvA) to study cell culture models for mitochondrial disease, in particular a patient-derived cell line containing a stable heteroplasmic deletion of mtDNA. Following his PhD he went for a 1-year postdoc to Louvain-la-Neuve, Belgium in the laboratory of Prof. Francoise Foury to develop an mtDNA-mutator human cell culture model using expression of dominant mutant versions of the mtDNA polymerase gamma. This work was continued in the laboratory of Prof. Howy Jacobs, in Tampere, Finland, where after a few years of working as a postdoc he established his own laboratory in 2001, following the seminal discovery of the long sought-after mtDNA helicase, Twinkle, that at the same time was established as an mtDNA maintenance disease protein/gene in close collaboration with Prof. Anu Wartiovaara and many others. In Finland, the Spelbrink lab was part of the Academy of Finland funded FinMIT Centre of Excellence for two consecutive 5-year periods also involving, amongst others, the laboratories of Prof. Jacobs and Wartiovaara. In 2008, Spelbrink was appointed tenure track Prof. in molecular cell biology at the University of Tampere. He moved back to the Netherlands as a senior researcher at the Radboudumc, Nijmegen, in 2010, having successfully obtained a large ‘Vici’ grant from the Dutch Research Council (NWO). After his move back to the Netherlands, Dr. Spelbrink shifted his focus more towards protein nucleic-acid protein interaction, developing and using high throughput mass spectrometry methods for the identification of factors involved in mtDNA maintenance and expression. Nonetheless, his focus is and has always been on understanding the molecular and cellular mechanisms of the mtDNA gene expression system.