Daan Panneman and Richard Rodenburg, theme Metabolic disorders, have been awarded a grant from Stichting Stofwisselkracht for their proposal entitled “CRISPR/Cas9 knock-in complementation in fibroblasts of mitochondrial disease patients”. Together with Omar Tutakhel and Jan Smeitink, they will investigate the possibility of using CRISPR/Cas9 knock-in to correct genetic variants in patient fibroblasts.
Mitochondrial disorders belong to the most frequently occurring metabolic disorders (incidence estimated 1:5000 live births). The disease onset can be at any age, involving different organs, and with a wide range of clinical signs and symptoms. Establishing a diagnosis is often challenging because of the large number of mitochondrial disease-causing genes (approximately 400 disease-causing genes described to date) and very limited genotype-phenotype correlations.
In the Radboud Center for Mitochondrial Medicine, Whole Exome Sequencing (WES) is used to identify pathogenic genetic variants in patients suspected of a mitochondrial disorder. Based on genetic, clinical, and biochemical data, a diagnosis is made. However, proving a causal relationship between the patient’s phenotype and genetic variants of unknown significance (VUS) is difficult. The current procedures for follow-up investigations to prove causality are time consuming and do not always give clear answers.With this funding we will attempt to optimize the ability to study the causality between VUSs that have been identified in patients and mitochondrial function by using CRISPR/Cas9. With this gene-editing technique, we will repairing the genetic variant in patient fibroblasts restores mitochondrial function. Based on this we can conclude whether the VUS is pathogenic. We postulate that this technique will increase the number of VUSs that can be resolved, improving the diagnostics of mitochondrial disorders and ultimately of other metabolic diseases.
Lowlands Science call for projects17 February 2020
Researchers pay attention! Lowlands is looking for research teams to participate in Lowlands Science 2020. It’s a great way to reach a large audience, do unique experiments with and on them, and to have a memorable experience with your colleagues.Read more
Five ZonMw ‘Off Road’ grants for Radboudumc researchers17 February 2020
Benoit Besson, Annemarie Boleij, Jonne Doorduin, Jorik Nonnekes and Sara Roig Merino have each received an ZonMw ‘Off Road’ grant of €100,000. The grants are intended for biomedical health researchers who dare to go off the beaten track in their search for new insights and unexpected breakthroughs.Read more
Dutch Kidney Foundation PhD grant for Johan van der Vlag and Tom Nijenhuis14 February 2020
Johan van der Vlag and Tom Nijenhuis, theme Renal disorders, received this grant for their joint research project “Targeting a novel paracrine signaling pathway between glomerular endothelium and podocytes to treat glomerular injury”.Read more
Interactive career day for Postdocs and PhD candidates13 February 2020
45 Postdocs and PhD candidates attended the first Interactive career day organised by Janssen Pharmaceutica, to learn more about career perspectives and R&D activities that on the longer term can lead to ideas and potential future collaboration.Read more
Khondrion begins study on optimal dosage of new drug10 February 2020
Pharmaceutical company Khondrion, a spin-off from Radboudumc, has taken another important step in the development of its drug sonlicromanol. The first patients have used the drug as part of a phase 2b study, which focuses on determining the optimum dose and efficacy.Read more