Translational models for peroxisomal dysfunction in genetic disease and malnutrition
The PERICO research programme aims to uncover how a central metabolic organelle, the peroxisome, participates in controlling cellular metabolism. Metabolism and metabolic control are emerging as important frontiers in physiology. This is because, in our rapidly changing world, we face the effects of both metabolic extremes – from obesity on the one hand to malnutrition on the other. Learning how to control energy metabolism is therefore one of the most pressing challenges of the 21stcentury.
Peroxisomes are key metabolic organelles, which must communicate and interact extensively with their environment to exchange metabolites and coordinate cellular responses. Membrane contact sites (MCS), where membranes of two organelles are physically tethered to enable rapid transfer of small molecules, enable organelle communication and are crucial for coordination of cellular functions and hence human health. Research on organelle interactions and communication is a challenging, upcoming field in current cell biology.
PERICO will exploit recent developments in high-throughput and genome-wide screening technologies, combine these with modern molecular cell biology and systems biology and ultimately translate the data into new leads for drug discovery and therapy.
Early Stage ResearchersThe training schemes include specific research projects, secondments to partner organizations, a wide range of dedicated courses, and workshops organized by the academic and industrial partners of the Network. The scientific training programme will be complemented with training in managerial soft skills.
The positions for Early Stage Researchers are available for candidates with a research experience ≤ 4 years (counted from the diploma that gives the rights to embark in a doctoral degree).
Candidates must not have resided or carried out their main activity (work, studies, etc) in the country of their host organisation for more than 12 months in the 3 years immediately prior to recruitment (short stays, such as holidays, are not taken into account).
RequirementsCandidates should have:
• exceptional academic performance, including qualifications, prizes
• subject specific skills and expertise (see project descriptions)
• communication, presentation skills and team working abilities
• competence in written and spoken English.
Length of appointment: 3 years
Type of contract: temporary
Starting date: April 1, 2019
Applicants can apply for multiple positions.
Reference: ESR3-NLA PhD position is available at the University Medical Centre Groningen, Department Paediatrics, Centre for Liver, Digestive and Metabolic Diseases, The Netherlands.
Project title: Translational models for peroxisomal dysfunction in genetic disease and malnutrition
In this ‘Systems Medicine’ project we will focus on the construction of computational models to understand how severe acute malnutrition (SAM) leads to sustained dysfunction of peroxisomal and mitochondrial metabolism. A challenge for such an approach is to bridge the gap between computational models and the in vivo metabolism in patient tissues. To this end the PhD student will also develop in vitro disease models, such as liver organoids and iPS-derived liver cell culture. Tasks include:
• Establish an in vitro model for SAM (liver iPS cells and/or organoids in medium deprived of amino acids).
• Biochemical characterization of the in vitro malnutrition model, focusing on fluxomics and proteomics.
• Construct a computational model of the interplay between peroxisomes and mitochondria in lipid metabolism.
• Model-informed interventions to rescue peroxisomal-mitochondrial function.
Location: Groningen, The Netherlands
Supervisor: Prof. Dr. B.M. Bakker (b.m.bakker01AT umcg.nl)
Co-supervisors: Prof. Dr. V. Martins Dos Santos, Lifeglimmer GmbH & Dr. R. Bandsma, The Hospital for Sick Children
Planned secondments: The Hospital for Sick Children, KU Leuven, Lifeglimmer GmbH
Required subject specific skills and expertise: A masters’ degree in life sciences, biophysics, biochemistry, or a related field, with clear affinity for metabolism and mathematics.
Application deadline: 17/02/2019
Starting date: April 1, 2019