The field of genetic disorders has been revolutionized in recent years through the advent of next-generation sequencing technologies. Functional assessment of the many identified genetic variants has traditionally been performed via dedicated diagnostic assays. Progress in high-resolution mass spectrometry have enabled more holistic approaches for metabolite profiling in body fluids and cells. The current project involves the establishment and application of cellular metabolomics for flux analysis. The goal is to provide a dynamic image of entire metabolic pathways to assess the functional consequences of mutations in genetic disorders of glycosylation and mitochondrial metabolism. In the longer run, this approach will be applied to additional genetic disorders, including known and newly identified gene defects.
The project is embedded in a large innovation project within the Translational Metabolic Laboratory (TML) of the Radboudumc to establish functional –omics methodologies based on mass spectrometry for disease gene identification and confirmation. The applicant will interact closely with bio-informaticians, mass spectrometry specialists, and staff and technicians specialized in various genetic disease groups.
The postdoc will establish and apply cellular metabolomics methodologies for flux analysis. You will be involved in the design and validation of existing and novel methods, with the goal to cover in first instance sugar metabolism and central carbon metabolism, with later extension to additional metabolic pathways. Additionally, you will support mass spectrometry developments in the metabolomics group, and will contribute to the evaluation of different approaches to extract high quality and clinically relevant information together with a post-doc bio-informatics and collaborate with a post-doc functional genomics to definitely confirm the functional consequences of genetic mutations.
Tasks and responsibilities
- Design and implement novel diagnostic methodologies using liquid chromatography-mass spectrometry (Triple Quad and QTOF);
- Contribute to creative solutions for the translation of complex data to a clinically relevant result, together with bioinformaticians, technicians and laboratory specialists;
- Active role in the further development of a mass spectrometry based metabolomics core;
- Share expert-level knowledge in an efficient way with collegues from different TML teams.
- Candidates should have a PhD degree in analytical chemistry or one of the molecular life sciences;
- Enthusiasm, curiosity and ambition to succeed in translational academic research;
- Expert knowledge on analytical chemistry, metabolomics and extensive hands-on experience with tandem- and/or high resolution mass spectrometry is a requirement;
- Preferably experience with metabolic flux analysis;
- Team-player, able to work cooperatively towards a common goal, excellent social skills;
- Capacity to share expert knowledge on different levels, both in a practical setting as well as in presentations;
- Effective in communication, accurate, flexible and independent worker;
- Affinity with laboratory patient diagnostics and working in a hospital setting.
The Translational Metabolic Laboratory (TML) harbors a range of top researchers in the area of inherited diseases including disorders of movement, mitochondrial disease, and protein glycosylation (CDG). Our work in recent years lead to recent publications in high-impact papers (Science, NEJM, Nature Genetics). The research in the lab is closely linked to other departments such as Genetics, Pediatrics, and Neurology. The combined infrastructure is state-of-the-art including innovative genetics tools (TALEN&CRISPR/cas9 technology, Next-Generation Sequencing, etc.), the Radboudumc Technology Center for Mass Spectrometry and a wide range of cellular functional assays. In addition, substantial research is performed in model cells and organisms using molecular biology tools to identify and investigate new disease genes.
TML is part of the Department of Laboratory Medicine and is active in the three core tasks of the Radboudumc: patient care, scientific research and education. The current focus of TML is to further develop its laboratory activities in functional genomics, metabolomics, proteomics and glycomics, in order to maintain its international strong position in research and diagnostics of inherited metabolic disease. The activities are performed within the scope of the Clinical Genetics Center Nijmegen.
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