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15 PhD Positions in Experimental and Computational Sciences: Polymers in the Liver - Metabolism and Regulation

University Medical Center Groningen

The PoLiMeR project http://polimer-itn.eu/vacancies/

To advance diagnostics and treatment of metabolic diseases beyond the state-of-the-art, a new generation of scientists is needed. The complexity of the metabolic network and its aberrant behaviour in disease require truly interdisciplinary researchers, trained in the three ‘pillars of Systems Medicine’: experimental, computational and clinical research. PoLiMeR aims to train you as a talented PhD student in this field. We bring together clinical, academic, and industrial experts on inherited metabolic diseases, computational modelling of the entire human metabolism, organ-on-chip technology, and detailed metabolic profiling, located in Germany, Luxembourg, Sweden, Norway, and the United Kingdom. You will be appointed at one of the 15 highly recognized academic or non-academic partners and develop your research skills to become a Systems-Medicine expert.

Job description

Metabolic diseases are a burden on the European population and health care system. It is increasingly recognised that individual differences with respect to history, lifestyle, and genetic make-up affect disease progression and treatment response. A Systems Medicine approach, based on computational models fed with individual patient data, has the potential to provide the basis for a personalised diagnosis and treatment strategy. The PoLiMeR consortium has identified the inherited, liver-related diseases of glycogen and lipid metabolism as the ideal starting point for innovative research training in personalised ‘Systems Medicine’. These diseases are life-threatening for children. Since each specific disease is rare, research efforts are diluted. Our system-based perspective opens possibilities for the application of novel drugs and diagnostic tools to a range of different diseases.

Within the Innovative Training Network PoLiMeR we are seeking for 15 PhD students for the project entitled 'Polymers in the Liver: Metabolism and Regulation' which is funded by the EU. We offer a challenging project in a highly international team of researchers. You will have your individual research project at your host organisation, focusing on your discipline of interest. To complement your specialized training, you will do internships at a complementary PoLiMeR partner organization. In addition, you will follow advanced interdisciplinary courses by leaders in the field of Systems Medicine. Thus, you will be trained to become a Systems-Medicine expert with expertise in computational and wet-lab techniques, who can collaborate between clinical, academic, and industrial environments.

Are you interested? Please, check the different PhD positions available in the PoLiMeR project below!

For a more detailed description of the PhD positions please visit the website: polimer-itn.eu/vacancies/

Challenge 1: Glycogen is a glucose-based polymer, comprising linear and branched components in a tree-like arrangement. Hence, an enzyme acting upon glycogen can cleave or rearrange the polymer backbone at multiple sites. The challenge will be to develop novel experimental and computational tools that can resolve spatiotemporal aspects of enzyme catalysis at the complex polymer surface and apply these to clinical samples and data to identify bottlenecks and therapeutic targets. 

PhD student 1: Kinetic analysis of enzymes in glycogen metabolism

Host organisation: John Innes Centre, Norwich UK*; contact: Rob.Field[at]jic.ac.uk 

PhD student 2: Structural analysis of glycogen from models and patients with Glycogen Storage Diseases

Host organisation: Iceni Diagnostics, Norwich UK*; contact: stephan.goetz[at]icenidiagnostics.com 

PhD student 3: Mathematical modelling of glycogen metabolism and glycogen-related disorders

Host organisation: Heinrich Heine Universität Düsseldorf, DE; contact: oliver.ebenhoeh[at]hhu.de 

Challenge 2: Enzymes are thought to have a specific affinity for one well-defined substrate. In contrast, enzymes acting on larger molecules catalyse the conversion of a functional group in the substrate with a lesser specificity for the remaining part of the molecule. This promiscuity results in a combinatorial explosion of different molecular species. The challenge is to develop innovative analytical methods and genome-scale modelling approaches to analyse and interpret complex lipid profiles in a meaningful way, and apply these to clinical samples and data to identify novel causes of patient-to-patient variability. 

PhD student 4: Quantitative and miniaturised assays for structure-resolved lipidomics

Host organisation: Leiden University, NL; contact: hankemeier[at]lacdr.leidenuniv.nl 

PhD student 11: Development of in vitro liver models for inborn errors in glycogen and fatty-acid metabolism

Host organisation: MIMETAS, Leiden NL*; contact: d.kurek[at]mimetas.com 

PhD student 6: Stoichiometric modularisation of combinatorial lipid metabolism

Host organisation: University of Luxembourg, LU; contact: ines.thiele[at]uni.lu 

Challenge 3: If enzymes catalyse multiple reactions, alternative substrates compete with each other for binding to the enzyme, thereby inhibiting each other’s conversion. At the level of metabolic pathways and networks this causes feedback and feedforward inhibition and may lead to complex dynamics. The challenge will be to develop novel experimental tools and computational models to analyse the impact of substrate competition on pathway dynamics, and apply these to patient samples and data to identify putative therapeutic targets. 

PhD student 9: Instability of glucose production in fatty-acid oxidation defects

Host organisation: University Medical Centre Groningen, NL; contact: b.m.bakker01[at]umcg.nl 

PhD student 12: Interplay between coenzyme and energy metabolism in fatty-acid oxidation defects

Host organisation: University of Bergen, NO; contact: Mathias.Ziegler[at]uib.no

PhD student 8: Dynamic computational modelling of lipid synthesis and storage in the human liver

Host organisation: Heinrich Heine Universität Düsseldorf, DE; contact: oliver.ebenhoeh[at]hhu.de 

PhD student 10: Dietary interventions and compensatory substrate switch in fatty-acid oxidation defects

Host organisation: Universitätsklinikum Freiburg, DE; contact: zkj.sekretariat.prof.spiekerkoetter[at]uniklinik-freiburg.de

Challenge 4: Metabolic fluxes and metabolite homeostasis are regulated extensively through gene expression and signalling. Recently, the physiological importance of autophagy-like pathways for glycogen and lipid metabolism has become apparent. The challenge is to develop novel experimental and computational methodologies to follow polymers in the cell and to integrate this spatial regulation with classical levels of regulation, potentially identifying novel mechanisms for patient-to-patient variability. 

PhD student 13: Multi-level regulation of metabolism in fatty-acid oxidation defects

Host organisation: University Medical Centre Groningen, NL; contact: b.m.bakker01[at]umcg.nl 

PhD student 14: Directing signal transduction pathways to establish novel therapies for glycogen storage disease I

Host organisation: University Medical Centre Groningen, NL; contact: m.h.oosterveer[at]umcg.nl 

PhD student 15: The role of autophagy and mTOR signalling in inborn errors of glycogen metabolism in hepatocytes

Host organisation: University Medical Centre Groningen (NL) and Carl von Ossietzky Universität Oldenburg; contact: kathrin.thedieck[at]uni-oldenburg.de

PhD student 5: Integrations of genome-scale models with signalling networks

Host organisation: KTH Royal Institute of Technology, Stockholm SE; contact: adilm[at]kth.se

Challenge 5: A key challenge in Systems Medicine research is making the extremely diverse data FAIR. FAIR means Findability, Accessibility, Interoperability and Reusability of data. Within this project we base ourselves on the FAIRDOMHub, a platform for FAIR data, and explore improving the findability of data using information retrieval methods. How can we enable users to store their results in a way that the results are most easily found, even if the query is imprecise?

PhD student 7: Data and model management and information retrieval

Host organisation: HITS gGmbH, Heidelberg DE*; contact: wolfgang.mueller[at]h-its.org

*The PhD will be employed and do the research at the host organisation. In addition, the PhD will be registered at a university where the PhD will do the thesis defence. 

What do we ask?

  • A(n) (almost) completed master’s degree in a discipline relevant to the PhD position(s) for which you apply
  • Strong motivation for scientific research in an interdisciplinary and international environment
  • Excellent English presentation and writing skills
  • Good organizational and communication skills, being a team-player

Successful candidates must fulfil the mobility criteria defined by the European Commission:

At the time of recruitment by the host organisation, researchers 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 the reference date.

What do we offer?

The PhD student will be appointed at and conform the conditions of the host organisation indicated for each position.

Additional information

For more information about a specific position please contact the person indicated for that position.

Applying for a job

You are invited to apply if you are interested in one or more of the PhD positions. Please use the digital application form on www.werken.umcg.nl or http://bit.ly/2n54dnY

Please indicate in your motivation letter for which PhD position(s) you are applying.

You can apply until 1 October 2018.

Immediately after sending the digital application form you will receive an email confirmation with further information.

Qualification Type: PhD
Location: Groningen - Netherlands
Funding for: UK Students, EU Students, International Students
Funding amount: €26,664 to €34,080
£23,714.99 to £30,310.79 converted salary*
Hours: Full Time
Placed On: 6th August 2018
Closes: 1st October 2018
   
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* Salary has been converted at the prevailing rate on the date placed
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