Overview
Topic status: We're looking for students to study this topic.
The family of FGF/FGFRs receptors has been shown to be important in many aspects of development and disease, especially cancer. Our lab identified mutations in FGFR2 in endometrial cancer and has currently identified mutations in 97/804 tumours analysed. Many of these have been reported previously in the germline associated with a variety of skeletal syndromes. Although some of these mutations have been extensively studied many have not and we have also identified a small panel of novel mutations not reported before in any disease. We hypothesize they all mutation result in receptor activation. We are specifically interested to determine whether the novel mutations result in ligand-dependent or ligand-independent receptor activation. This project will have translational impact as it will speak into the clinical utility of blocking ligand binding as a therapeutic option.
Hypothesis: We hypothesize that mutations identified in FGFR2 in endometrial tumours activate the receptor by one of several mechanisms including affecting ligand binding and promiscuity, receptor dimerization, receptor recycling, and kinase activity.
Aim 1: Generate mutant FGFR2 expression constructs using site directed mutagenesis
Aim 2: Assess receptor activation using a combination of biochemical techniques and functional readouts of biological activity
Methods and techniques that will be developed in the course of this project:
- Site directed mutagenesis, plasmid preps, sequencing, cell culture, transfection, selection of stable cell lines
- Western blotting, immunoprecipitation, intracellular signalling, cell surface
- biotinylation and metabolic labelling to assess receptor recycling
References:
- Gartside MG et al., Mol Cancer Res. 2009 7): 41-54.
- Byron SA, et al., Cancer Res. 2008 68: 6902-7.
- Pollock PM, et al., Oncogene. 2007 26: 7158-62.
- Study level
- PhD, Honours
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
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Please contact the supervisor.
Dr Pamela Pollock
Professor Judith Clements
