Netherlands: Phd in Biomedical Sciences, chemistry

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The PhD student investigates diverse interactions of digitalis-like compounds with the sodium pump and ABC transport proteins.

•Designs and performs scientific research in the area of molecular pharmacology, toxicology and biochemistry

•Generates and analyzes data in order to contribute to scientific publications and presentations at scientific meetings

•Works in a team with other students and scientists to discuss, plan, and perform research in a stimulating environment

•Completes the project with a scientific dissertation

Requirements


University Graduate
MSc degree in Biomedical Sciences, Molecular Life Sciences, Biochemistry, Pharmaceutical Sciences

•Experience with molecular biology techniques

•Strong motivation to succeed in scientific research and well-structured working style

•Excellent communication skills

•Well developed social skills directed to work in a team and fluent in English

•Experience with structure-function relationship of transport proteins is a plus

Additional information about the job:
Digitalis-like compounds: new molecular interactions of an ancient arrow poison

Long before the discovery of the sodium pump (Na,K-ATPase) its
inhibitors were known. These compounds were originally used for the
preparation of arrow poison and during the past two centuries as
therapeutics in the treatment of congestive heart failure and atrial
fibrillation. Common preparations include digitalis, digitoxin,
digoxin, and ouabain. There is overwhelming evidence that
digitalis-like compounds (DLCs) are also endogenously present in
mammals and that these compounds function as hormones. Although it has
been established that endogenous DLCs also inhibit Na,K-ATPase,
additional mechanisms, such as DLC transport and cellular signalling,
most likely determine their physiological activity. Indeed some DLCs
have been shown to activate a signal transduction pathway. Digoxin has
been identified as a substrate of two members of the ATP binding
cassette (ABC) transporter family: ABCA8 and ABCB1 (P-glycoprotein,
MDR1). Current knowledge of the true physiological activities of DLCs
is fragmentary. The specific interaction between DLCs and Na,K-ATPase
is still unresolved. The Na,K-ATPase amino acids involved in the
pathway from DLC binding to signal transduction cascade are unknown,
and also DLC transport proteins and their DLC-binding pockets are
enigmatic.

In this project we want to elucidate the molecular determinants of
DLC action. The research strategy comprises all three levels that are
important for this action:

1. Molecular interaction between DLCs and Na,K-ATPase.

2. Signal transduction by DLC through the sodium pump.

3. Molecular mechanisms of DLC transport.

For development of new DLCs that could stimulate Na,K-ATPase
activity and/or antagonize endogenous DLCs the narrow therapeutic index
might be a life-threatening problem. Therefore, detailed knowledge of
the molecular determinants of DLC activity will not only provide
valuable new scientific insights, but may also have important medical
implications in the long run.

Keywords: digitalis-like compounds; ouabain; Na,K-ATPase; ABC-transporters; binding site

Organization


Radboud University Nijmegen Medical Centre Pharmacology and Toxicology

The molecular section of the department has a
traditional strength in the field of drug transport and toxicity. The
objective of the section is to examine the molecular and cellular
mechanisms by which compounds foreign to the body are handled by
transport proteins, with special reference to the role of these
processes in drug efficacy and safety.

Conditions of employment


Employment basis: Temporary for specified period
Duration of the contract: 4 years
Maximum hours per week: 36

Additional conditions of employment:
•Salary level 10A: maximum € 2572 gross per month

Additional Information


Additional information about the vacancy can be obtained from:

Mr. Dr. J.B. Koenderink, assistant professor
Telephone number: (024) 361 4639

Mr. Prof. Dr. F.G.M. Russel, professor
Telephone number: (024) 361 6892

 
Or additional information can be obtained through one of the following links.

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Application


You can apply for this job before 26-12-2008 by sending your application to:

UMC St Radboud
155 CBEG
M. Korsten, HR consultant
Postbus 9101
6500 HB Nijmegen

E-mail address: CBEG-solliciteren@cbeg.umcn.nl

When applying for this job always mention the vacancy number AT 08907.

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