The Division of Analytical Biosciences of the Leiden/Amsterdam Center for Drug Research (LACDR) and the Departments of Neurology and Human Genetics of the Leiden University Medical Center (LUMC) wish to appoint a;
PhD Student in the field of Metabolomics and Chemometrics
(38 hours per week)
Vacancy number: 11-269
The project: Neurochemistry of migraine in patients and models, zooming into the cause
Migraine is a prevalent multifactorial neurovascular disease; most molecular mechanisms leading to migraine attacks are still unknown. Genes for monogenic familial hemiplegic migraine (FHM) and the common forms of migraine seem to point to a central role for abnormal ion and neurotransmitter levels, especially glutamate, in the brain. The introduction of FHM gene mutations into the mouse has led to translational animal models for the disease that allow unraveling of disease mechanisms. Metabolic processes are at the core of physiology. Hence, metabolic profiles are indicative of changes in metabolic pathways and allow identification of changed connectivity between metabolites (and other biomolecules). The dynamics of (diseased) biochemical processes (such as a migraine attack!) can be followed in vivo in even greater detail by using isotopically-labeled metabolite tracers within a metabolomics approach. Metabolomics studies of human CSF that were performed as a collaborative effort between LACDR (Analytical Biosciences) and LUMC (Neurology and Human Genetics) revealed interesting potential biomarkers of migraine, hinting towards changes in metabolism of neurotransmitters, polyamines, and endogenous antioxidants. The search for migraine biomarkers is a continuous research effort; when new metabolomics platforms will become available they will be applied to these samples. Importantly, more research is required to determine causal relations between observed changes in metabolic profiles and their biological interpretation. This can be achieved by the development and application of atomic-resolved metabolomics by using 13C/15N labeled tracers and analyzing how these isotopes are implemented at the atomic level within pathways over time.
Tasks:
The PhD student will develop the statistical and computational parts of the analytical technology for tracer-based studies of brain metabolome dynamics. Components of this statistical part include designing and planning of the different substudies, preprocessing of the tracer metabolomics (GC-MS, LC-MS) data, statistical analysis and biological interpretation of the outcome. The development of tracer metabolomics will be done in collaboration with dr. Hiller (Luxembourg Centre for Systems Medicine), who developed similar techniques using cell lines and GC-MS. Tracer-based metabolomics will be applied to study metabolism of cell cultures and ex-vivo brain slices of migraine mice, followed by studies of in vivo brain biochemistry monitored by microdialysis. Metabolomic profiles in the basal state will be compared with those after experimentally triggered cortical spreading depression (CSD), the correlate of a migraine attack, and drug intervention. Biological interpretation of observed changes will be supported by a developed model of brain metabolism and parallel neurobiology research that is performed at the LUMC; both will guide new possible intervention options. The identified pathways will be validated in tracer studies in migraine patients. This multidisciplinary approach will further improve our understanding of abnormalities in neurochemistry relevant to migraine.
Requirements:
We are looking for a motivated researcher who obtained her/his master degree in a research project in which bioinformatics or data analysis of complex sets of biomolecules obtained in biological related studies played an important part. Experience with (multivariate) statistical analysis, programming (e.g. Matlab and/or R), construction of correlation networks and/or longitudinal data analysis is desirable. The use of isotopic tracers is crucial in this project and therefore the candidate should be proficient in reading structural formulas, reaction schemes and mechanisms, including all stereochemistry aspects. It is very important that the student will be able to trace a given atom or moiety through a complex set of reactions. For that reason a chemical background with strong knowledge in biochemistry is essential. The researcher should have a strong interest in biology-driven research and be able to work in a multidisciplinary team.
We offer:
We offer a vibrant environment to develop on-the-job the skills and networks that a successful academic needs. Appointment will be according to the terms of the Collective Labour Agreement of Dutch Universities (CAO Nederlandse Universiteiten), for a period of one year with an extension of three years after positive evaluation of capabilities and compatibility. Ultimately the appointment must lead to a completion of a PhD thesis.
The gross monthly salary is set on € 2.042,- in the first year up to € 2612,- in year four. An appointment with Leiden University includes a pension build-up and facilitates other benefits such as an annual holiday premium of 8% and an end-of-year premium of 8.3%.
All our PhD students are embedded in the Leiden University Graduate School of Science http://www.research.leiden.edu/phd/phdprogrammes/programmes.html. Our graduate school offers several PhD training courses at three levels: professional courses, skills training and personal effectiveness. In addition, advanced courses to deepen scientific knowledge are offered by the research school.
Further information
For more information, please contact Dr. Theo Reijmers (t.reijmers@lacdr.leidenuniv.nl) , phone +31 71 5274320).
Additionally, you can visit the websites of the Faculty of Science: http://www.science.leidenuniv.nl/.
More information about employment at Leiden University can be found via: http://www.leiden.edu/.
Applications:
Do you identify with the profile above and do you aspire to have a career in research? Please apply by sending your written application before 1 February 2012, using the vacancy number, including full Curriculum Vitae and the names and phone numbers of two references to the attention of:
Prof. Dr. Thomas Hankemeier ( hankemeier@lacdr.leidenuniv.nl) or Dr. Arn van den Maagdenberg (A.M.J.M.van_den_Maagdenberg@lumc.nl).
