Leiden/Amsterdam Center for Drug Research / Division of Toxicology

Organisation
The division of Toxicology is part of the LACDR. The overall mission of the division is to understand the signal transduction networks in cancer development, progression and treatment with the ultimate aim to develop better and safer anticancer therapies. A strong emphasis is on breast cancer and the application of functional genomics and transcriptomics approaches in our research in combination with systems microscopy.

Project Description
The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are closely related receptor tyrosine kinases that are related to metabolism and survival/growth signaling. The IGF1R is implicated in breast cancer development. The use of insulin-like homologues in diabetes requires a strict selectivity for the insulin receptor, to prevent safety issues related to cancer development. In this project we will define the differential mechanism by which insulin homologues activate these receptors and the downstream signaling events involved. We will relate these findings to mammary gland tumour formation in p53-mutant mouse models. We will perform systematic gene expression profiling to develop a strategy based on toxicogenomics that will allow future risk assessment of novel insulin-like compounds. The results should lead to a better definition of the safety of insulin homologues.

This work will be part of a close collaboration with the Centre for Biological Medicines and Medical Technology (BMT) at the National Institute for Public Health and the Environment (RIVM; www.rivm.nl) in Bilthoven, a recognized leading centre of expertise in the fields of health, nutrition and environmental protection. The BMT is assessing the dossiers for human pharmaceuticals for marketing authorization on pharmacology and toxicology on behalf of the Medicines Evaluation Board and the European Medicines Agency.

Job Description
The PhD will work in a team and apply molecular and cellular biology approaches to decipher insulin homologue signalling. This involves ectopic expression of IR and IGF1R in relevant cell lines, stable lentiviral shRNA-based knock down approaches, qRT- PCR, systematic analysis of cell signalling pathways and genome-wide mRNA expression profiling. Together with a technician the responses with regard to mammary gland tumorigenesis in established p53-mutant mouse models will be analysed.

Who are we looking for?
The candidate should be an ambitious, highly motivated and enthusiastic person with good communication skills and experience in molecular and cellular biology techniques. Preferentially the candidate should have some experience with laboratory animals. The candidate must have a MSc degree in (Medical) Biology, Bio-Pharmaceutical Sciences or a related subject.

What do we offer?
Appointment will be according to the terms of the Collective Labour Agreement of Dutch Universities (CAO Nederlandse Universiteiten), initially for the duration of one year. An extension of 3 years is possible after positive evaluation of capabilities and compatibility. The salary will be set on € 2042,- per month in the first year up to € 2612,- in year four. Leiden University also offers an annual holiday premium of 8% and an end-of-year premium of 8.3%. You will be a member of the Graduate school of the Faculty of Science and participate in our PhD training program.

More information/applications
For more information, please contact Prof.dr. B. van de Water (LACDR)
Telephone: +31 (0)71 527 6223 or Dr. Jan Willem van der Laan (RIVM): +31 (0)30 274 2904. Additionally, you can check the websites of the Faculty of Science and the division of Toxicology: www.science.leidenuniv.nl  and http://toxicol.lacdr.gorlaeus.net 

For more information on the National Institute for Public health and the Environment see www.rivm.nl/preventie/geneesmiddelen 

Further information on employment at Leiden University can be found at: www.medewerkers.leidenuniv.nl 

Do you identify with the profile above and are you looking for an interesting job? Please apply by sending your written application, using the vacancy number, including a full Curriculum Vitae, and a list of publications, before July 9th 2010, to:

To the attention of: Prof.dr. B. van de Water. Preferably by e-mail: water_b@lacdr.leidenuniv.nl
Or by regular mail: LACDR / Division of Toxicology, Postbus 9502,
2300 RA, Leiden, The Netherlands

publication date: 16-06-2010