The structure and function of the IGF2 receptor.

Our aim is to characterise the protein-protein interactions between the IGF2 ligand and the IGF2 receptor, as well as the interactions of mannose-6-phosphate containing ligands, such as lysosomal enzymes, with other domains of the same receptor. Site directed mutagenesis and surface plasmon resonance (BIAcore) of recombinant proteins form the basis of a systematic analysis of the interacting amino acids and general stereochemistry involved in these ligand receptor interactions. Other studies include the directed evolution of IGF2R using surface display libraries and time-resolved analysis of cargo driven subcellular localisation of the receptor. The group collaborates closely with structural biologists at the University of Bristol (Professor Matt Crump) and at the University of Oxford (Professor Yvonne Jones, STRUBI).

 

 

 

 

 

 

    The functional genetic interactions of Igf2 and Igf2r in conditional murine models.

The gene expressing IGF2 (Igf2) is reciprocally imprinted with respect to the gene expressing the IGF2 receptor (Igf2r). Modification of DNA methylation and genomic imprinting implicate a role for loss of imprinting of IGF2 as a functional modifier of cancer risk. The purpose is to quantify allelic supply of the ligand and receptor in established genetic models of cancer progression. The initial focus has been on the functional genetics of Igf2 and Igf2r. These experiments are being extended to other tumour susceptiblity models using Cre mediated conditional gene disruption. The ultimate aim is to investigate the functional consequences of cell type domain specific expression within tumours, and their functional significance in tumour growth control.

                        

 

  

The identification and validation of IGF2 biomarkers

This research project is concerned with defining the specificity of insulin-like growth factor 2 (IGF2) signalling and uses microarray gene expression profiling, imaging and bioinformatic approaches to identify biomarkers associated with excess supply of IGF2 ligand.

 

 

 

  The generation and development of soluble forms of the IGF2 receptor domain 11 as ligand trap for IGF2.

          The purpose is to functionally evaluate therapeutic proteins that function as ligand traps for IGF2. The experiments focus on generating novel   

           forms of sIGF2R based on domain 11 of the receptor, evaluating ligand binding properties using surface plasmon resonance, and generating  

           genetically modified cell systems as assays. Collaboration with Cancer Research Technology aims to exploit these molecules for development

           and testing in early phase clinical trials run by the group in the Oxford Cancer Centre.

 

 

Translational research in bone and soft tissue sarcoma.

Bone sarcoma are high grade tumours that occur in young people. The current treatments result in 60% of patients being cured, but these treatments are associated with side effects. We are studying biomarkers that may influence treatment decisions and that will be tested in clincial trials. We collaborate with pathologists and surgeons at the Nuffield Orthopaedic Centre and other centres across Europe.

       

 

 

HealthTIES

The HealthTIES consortium joins five of Europe’s top regions for healthcare technology and addresses Europe’s greatest health challenges: an ageing population and the sustainability of the healthcare system.  The aim is to speed up the cycle of innovation and make the EU a world-class player in healthcare technology.