Doktorand/utbildningsplats

Sahlgrenska akademin utlyser doktorandplatser med placering vid institutionen för biomedicin, institutionen för medicin och institutionen för neurovetenskap och fysiologi.

Doktorandplatserna avser två års utbildningsbidrag och två års doktorandanställning, alternativt fyra års doktorandanställning, och beräknas leda fram till doktorsexamen.

För mer information och ansökningsblankett se:
http://www.sahlgrenska.gu.se/doktorandportalen/Doktor_Fran_start_till_mal/doktorandplatser

PhD Projects at Institute of Neuroscience and Physiology
Metabolic fate of artemisinin antimalarials

Application deadline: 2010-09-21

Description of the research project
Artemisinin, a sesquiterpene lactone endoperoxide, is the parent compound of a new class of antimalarials, which have a uniquely rapid onset of action also against multidrug resistant strains of P. falciparum.
Although the mechanism of action has not been fully established it appears that alkylating carbon-based radicals are formed damaging the parasites.This suggests a toxicity risk to also the patient host.The relationship between metabolic or chemical breakdown of these compounds in the body and toxicity is poorly understood.

The metabolic pathways of artemisinin will be investigated using both in vitro metabolic systems as well as human samples.These will be analyzed using LC-MS/MS for which an analytical method will be established.The generation of reactive products may be studied using different methods including trapping and glutathione conjugation.Potential pathways can possibly be studied in electrochemical in vitro systems mimicking oxidative CYP-mediated reactions.The extent of, and mechanism for, CYP2B6 inhibition of artemisinin and its derivatives will be investigated in vitro and results extrapolated by model simulation to the clinical situation.This research will contribute to a further understanding of the metabolism of artemisinin and its derivatives and its possible relation to toxic effects.It will highlight the clinical relevance of possible drug-drug interactions with regards to CYP2B6 inhibition.

Desired background
It is desirable that the candidate has a strong background in the pharmaceutical sciences with specialisation in pharmacokinetics and/or drug metabolism.Experimental experience with animals and in drug metabolism is an advantage.