Post-doc or PhD position Netherlands Metabolomics Center
Prednisolone induced metabolite profiles in human and mouse: Crossspecies
translation and cross-omics integration.
A 3-years post-doc position or 4 years PhD student position is available within
the Netherlands Metabolomics Center, in a joint project between Schering-
Plough, Leiden/Amsterdam Center for Drug Research (LACDR), TNO Zeist and
Radboud University Medical Center Nijmegen.
Summary of the project
Prednisolone and other glucocorticoids (GCs) are very potent
immunosuppressive and anti-inflammatory drugs that are used in more than 300
different indications. Although very effective, prolonged use at high dose is
hampered by side effects of which especially metabolic side effects are evident.
These metabolic side effects induced by prednisolone include osteoporosis but
also, fat redistribution, induction of insulin-resistance and beta-cell dysfunction,
leading to a serious condition that is strongly associated with elevated risk for
cardiovascular disease and type 2 Diabetes. Despite the fact that prednisolone is
a relatively old drug (introduced in the 50’s of the last century) the molecular
mechanisms by which its side effects are mediated are largely unknown. To
allow for a more rational development of an improved GC it is crucial to
understand the molecular mechanisms by which prednisolone induces side
effects.
In this project human healthy volunteers and mice will be treated with the
synthetic glucocorticoid prednisolone. In these studies, urine, blood and serum
samples will be taken and analyzed by metabolomics, transcriptomics and
proteomics techniques. These data will be integrated to
i) use state of the art techniques to increase our understanding of the biological
mechanisms underlying side effects of prednisolone
ii) identify biomarkers of glucocorticoid side effects that translate from mouse to
human
iii) allow for a more rational development of an improved GC.
Function description
The project is an Associate Project of the research program of the Netherlands
Metabolomics Centre (http://www.metabolomicscentre.nl/). Within this centre,
Core Projects are aimed at method development whereas Associate Projects
apply these methods within research programs.
The project is a collaboration between teams from Schering-Plough in Oss, the
Leiden/Amsterdam Center for Drug Research (LACDR) in Leiden, the Radboud
University Medical Center Nijmegen and TNO in Zeist.
You will be responsible for the statistical and biological analysis of the crossomics
data that are produced within the project. Analysis methods to be used
include advanced statistical methods for multivariate analysis, data fusion and
experimental design; pathway analysis; sequence homology analysis; text mining;
integration of experimental data and prior knowledge. The focus will be on
generating biological hypotheses by applying existing methods and methods that
will be developed within the core projects of the NMC, rather than independently
developing new statistical or bioinformatics methods. You will work together with
scientists in Oss, Leiden, Zeist and Nijmegen to identify the methods that are
most suitable for the goals of the project. You will discuss and where possible
initiate desired new methodology development with project partners and with
scientists from NMC Core Projects. You will also be responsible for initiating and
analyzing additional in-vitro or in-vivo experiments. You will interact with the NMC
groups involved in metabolite quantification and identification, and spend some
time at the NMC Demonstration and Competence Lab in Leiden where the
metabolomics experiments are performed.
You will be appointed at the LACDR, and will be stationed bi-locally at Schering-
Plough in Oss (approx 60-70% of the time) and at the project partners in Leiden
and Zeist (30%-40%).
Profile of the candidate
The ideal candidate has a degree in bioinformatics with a strong proven interest
in biology, or alternatively a degree in biology or biochemistry with skills in
bioinformatics and/or biostatistics. We are looking for a candidate with excellent
communication and interpersonal skills to work successfully with the project
partners at Oss, Zeist, Leiden and Nijmegen.
More information
For more information you may contact prof. Thomas Hankemeier (Leiden
University, principal investigator) or dr. Wynand Alkema (Schering-Plough,
project leader).
Contact information Thomas Hankemeier: hankemeier@lacdr.leidenuniv.nl, +31
(0)71 527 4226.
Contact information Wynand Alkema: wynand.alkema@spcorp.com, +31 (0)412
663059.
