Genetic mouse models and in vivo studies

Early stage researcher 14 (ESR14) project – Joyce Koenen
Supervision: Prof S Offermanns, Dr N Wettschureck, Dr S Tunaru, Dr A Sassmann, Dr S Tonack
Host: MPG (DE) – Max Planck Institute for Heart and Lung Research, Dept. of Pharmacology I- Project proposal:

I. Proposal

Aim:
1. Generation of mouse lines expressing mutated GPCRs with altered pharmacological and signalling properties.

2. Analysis of GPCR expression level and localization using transgenic/genetic approaches.

3. Phenotyping mice with mutated GPCRs for pharmacological and signalling properties.

4. Evaluation of GPCR modulators in in vivo heterotopic xenograft model systems.

Methodology:
BAC (Bacterial Artificial Chromosome) transgenics, constitutive and conditional mutagenesis, tumor growth and metastasis studies, calorimetry, insulin/glucose tolerance assay, ex vivo study of mitochondria function.

Planned secondments: INSERM (FR), UGL (UK).

 

II- Requirement candidate:

Required diploma: MSc degree in molecular / biomedical life sciences

Required expertise: molecular biology, genetics, biochemistry

Recommended expertise: animal handling and experimentation, imaging

Key publications:
1. Tang C, Ahmed K, Gille A, Lu S, Gröne HJ, Tunaru S, Offermanns S (2015) Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat. Med. 21, 173.

2. Offermanns S (2014) Free Fatty Acid (FFA) and Hydroxy Carboxylic Acid (HCA) Receptors. Annu. Rev. Pharmacol. Toxicol. 54, 407.

3. Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S (2013) Platelet-derived nucleoides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 24, 130.

4. Blad CC, Tang C, Offermanns S (2012) G protein-coupled receptors for energy metabolites as new therapeutic targets. Nat. Rev. Drug Discov. 11, 603.

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e.v.langemeijer@vu.nl

ONCORNET Coordinator
Vrije Universiteit Amsterdam