Research Scientist
Proffice Sverige AB / Biomedicinjobb / Göteborg
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Title:
Development of a novel application of the lung slice methodology to increase the understanding PKPD relationships of anti-inflammatory substances
The project will be conducted at AstraZeneca at the department of Drug Metabolism and Pharmacokinetic (DMPK) in Mölndal. Inflammation is one of AstraZeneca's key areas of research and several therapeutic targets are of inflammatory character and the search for novel anti-inflammatory substances is ongoing. In this project we want to explore pharmacodynamic responses in a lung slice methodology that was originally developed to study of lung pharmacokinetic drug properties. Previous work has shown that a pro-inflammatory challenge of lung slices with lipopolysaccharide (LPS), one of the most potent immune-activating stimuli known, results in significant release of inflammatory mediators such as tumor necrosis factor (TNF)-? and interleukin (IL)-1?. With the usage of lung slices several time points after inflammatory challenge can be studied as well as different drug pre-treatment times or regimes, all with an assumed lower variability compared to in vivo. With the potential to study in detail both drug-related and system-related time-dependencies of a concentration-response relationship, a more complete picture could arise and accelerate the understanding and modeling of PKPD relationships for anti-inflammatory substances.
Project plan:
The aim of the project is to find optimal conditions under which testing of anti-inflammatory substances can be performed in lung slices. Use the lung slice methodology to produce viable fresh tissue lung slices from rats. Administer an inflammatory challenge (LPS) to the slices and measure the inflammatory response (TNF-?, and/or IL-1?) of lung slices at different time points on protein level with ELISA, total protein content can be measured with BCA. In a second study an anti-inflammatory substance is administered before the challenge in various concentrations and various pre-treatment times and the inflammatory response is measured over time for each treatment. Thirdly PK/PD modeling can be applied to the data.
Methods:
Animal work including organ sampling and slicing of lung tissue, protein measurement with ELISA and BCA, drug analysis by LC-MS, and modeling in Phoenix if applicable.
Student background:
Pharmacist, biomedical scientist or similar with experience of work laboratory animals (theoretical or practical). Modeling skills is a plus, but secondary to experimental skills.
For more information please contact:
Erica Bäckström
erica.backstrom@astrazeneca.comVi söker främst dig som studerar på Apotekarprogrammet eller studerar Biomedicin
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www.proffice.sePubliceringsdatum2014-03-21Så ansöker duSista dag att ansöka är 2014-04-04
Ange följande referens när du ansöker: 200560596
Klicka på denna länk för att göra din ansökanKontaktGabriella Barle
FöretagProffice Sverige AB
AdressProffice Sverige AB
Jobbnummer 1815712
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