6 PhD Positions, Marie-Curie ITN “PoLiMeR”, Europe (2019)

PhD positions
Enzyme catalysis at the polymer surface
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: Mathematical modelling of glycogen metabolism and glycogen-related disorders
Host organisation: Heinrich Heine Universität Düsseldorf, DE
contact: oliver.ebenhoeh[at]hhu.de

The PhD student will develop a computational model to study overall dynamics of glycogen formation and analyse which parameters determine the structural properties of glycogen, such as branching pattern and size. The PhD student will reproduce metabolic disorders related to glycogen metabolism and develop intervention strategies how to counteract glycogen-related metabolic disorders by drug applications.

PhD student 2: Quantitative and miniaturised assays for structure-resolved lipidomics
Host organisation: Leiden University, NL
contact: hankemeier[at]lacdr.leidenuniv.nl

The PhD student will develop novel analytical methods for lipid profiling, and thereby will focus on detailed analysis of modified lipidsand to identify structural isomers.This will be achieved using hydrophilic interaction chromatography (HILIC) or normal phase liquid chromatography (NPLC)-based separation coupled to a reversed-phase liquid chromatography (RPLC)-mass spectrometry analysis. The methods developed will be miniaturised to allow the analysis of biomass-limited samples, such as patient-derived iPS hepatocytes or organ-on-a-chip samples.

PhD student 3: Stoichiometric modularisation of combinatorial lipid metabolism
Host organisation: National University of Ireland, Galway, IT
contact: ines.thiele[at]gmail.com

The PhD student will develop a novel approach to represent promiscuous enzymes (enzymes acting on lipid classes rather than on single lipid species) more efficiently in a genome-scale model (GEM). This innovation will be implemented in a comprehensive genome-scale model of human metabolism. The problem of combinatorial explosion of possible lipid molecular species in current computational models will be addressed by dividing the existing reactions for synthesis of complex lipids into a set of modular synthesis and degradation reactions, based on the concept of conserved moieties, resulting in a stoichiometric matrix that admits integral flows (integer reaction rates). Each integral flow shall represent the synthesis and degradation of a different combination of lipid molecular species. The PhD student will map lipidomics data in the metabolic network analyse computationally different disease specific scenarios.

hD student 4: Interplay between coenzyme and energy metabolism in fatty-acid oxidation defects
Host organisation: University of Bergen, NO
contact: Mathias.Ziegler[at]uib.no

The PhD student will identify alterations of NAD and CoA coenzyme metabolism in mitochondrial fatty-acid oxidation (mFAO) deficient liver cells. Furthermore, the PhD student will modulate the availability of these coenzymes by pharmacological and genetic interventions and analyse the impact on energy metabolism, using metabolomics and 13C-fluxomics. The interventions will be done in cell cultures of mFAO-deficient hepatocytes or patient-derived fibroblasts.

PhD student 5: 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

The PhD student will focus on construction and validation of a dynamic model of lipid synthesis based on ordinary differential equations and detailed kinetic data. Patients with defects in the mitochondrial fatty-acid oxidation (mFAO) accumulate acyl-CoA esters which are substrates for chain elongation into longer lipids. The PhD student will connect the lipid synthesis model to an existing and experimentally validated mFAO model and explore pathway stability and lipid profiles in various mFAO disorders and at different diets.

PhD student 6: Data and model management and information retrieval
Host organisation: HITS gGmbH, Heidelberg DE
contact: wolfgang.mueller[at]h-its.org
You will be employed and do the research at HITS. In addition you will be registered at the University Medical Center Groningen (NL) to obtain the PhD degree.

The PhD student will provide FAIR data management services to the PoLiMeR consortium based on the FAIRDOM Hub (the data sharing site hosted at HITS) and on GitLab. The PhD student will use the database generated in the PoLiMeR project together with pre-existing and public data in the to determine how changes in data collection, metadata quality and data feature extraction affect the information that can be found. The PhD student will seek to improve existing tools for data collection as well as querying at critical points.

We are looking for graduates in computer science who are aiming for a Doctorate. This topic is particularly interesting in that it provides quite general challenges (How to I tailor information retrieval and information storage algorithms such that they work best in combination?); at the same time, there are *real* users to cater to. These users can help in finding out the best combination of data enrichment/search algorithm in real life, in an exciting application area: The life sciences.

Eligible candidates for a PhD position in the PoLiMeR training network should have the following qualifications:
- A(n) (almost) completed master 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 organisational and communication skills, being a team-player

For more information, please visit the following link:
6 PhD Positions, Marie-Curie ITN “PoLiMeR”, Europe (2019)