PhD Project Candidate Blood-brain barrier drug targeting by mass spectrometry imaging in early ADME profiling



We have an open position for a PhD candidate at the Biomolecular Imaging and Proteomics, National Laboratory for Mass Spectrometry Imaging, Dept. of Pharmaceutical Biosciences, Uppsala University (UU), Sweden. This project is part of the EU-funded project ARIADME: Analytical Research in ADME profiling (http://pharm.kuleuven.be/pharbio/ariadme). ARIADME is a Marie Curie project which involves 4 academic centers and 10 industrial partners. The PhD candidate will be enrolled in the UU doctoral school program and is expected to contribute to network wide training events of the ARIADME project. The scientific objectives and tasks of this 4-year PhD research project can be summarized as follows.

Objectives:
The main objective of this project is to develop a novel approach utilizing mass spectrometry imaging (MSI) for direct quantitation of compounds targeting the central nervous system for unprecedented in-depth understanding of the blood-brain barrier (BBB) drug transport. The BBB presents a major obstacle in the development of drugs that are targeted for the central nervous system. MSI is a technique used to visualize the spatial distribution of e.g., drugs, drug metabolites, biomarkers, metabolites, peptides or proteins by their molecular mass directly in tissue sections. The specific aims are:

  • To develop a novel MSI approach to elucidate neurochemical associations between drug administration and BBB uptake
  • To apply the novel method to BBB in vivo models for investigation of transport and metabolism of drugs
  • To link and validate the results obtained by the novel MSI approach to other BBB drug uptake methods
  • To explore the usefulness of the MSI method in early ADME studies

Main Tasks:

  • A MSI methodology will be used for quantitation and visualization of drugs targeting the central nervous system. MSI has the advantages over other imaging methods that it does not involve radioactive labeling and allows simultaneous identification and visualization of the parent molecule, metabolites and endogenous compounds
  • Absolute drug and drug metabolite concentrations will be measured directly in brain tissue sections at high-spatial resolution
  • Drugs with known BBB distribution, transport mechanisms and metabolic patterns will be studied utilizing MSI and compared with other BBB drug uptake methods
  • The MSI approach will be applied to determine BBB penetration of a novel class of CNS-targeted drugs as part of the student’s industry secondment

The highly motivated candidate should hold an MSc degree in Pharmaceutical Sciences, Biomedical Sciences, Chemistry or a related field. Prior experience with mass spectrometry is desirable. He/she should have less than 4 years of research experience and must not have resided or carried out their main activity in Sweden for more than 12 months in the 3 years immediately prior to their recruitment*. Applications, including Resume/CV and Cover Letter, should be sent to Dr. Per Andrén ([email protected] via the Apply button below) or Dr. Maria Karlgren ([email protected]) no later than 10 November 2013.

* More info: http://ec.europa.eu/research/mariecurieactions/about-mca/actions/index_en.htm

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