Structural characterisation of the insulin-like growth factor (IGF) binding proteins and IGF receptors, their interactions with other physiological molecules and alterations in metabolic disorders

The main objective of the project is to study the structure of the insulin-like growth factor (IGF) binding proteins (IGFBPs) and receptors (IGF-Rs) and the formation of complexes with other molecules. The structure of IGFBPs and IGF-Rs is modified post-translationally by proteolysis, glycosylation, phosphorylation and polymerisation, and the factors that may have an influence on these processes are nutrition, physical activity, metabolic and other disorders. IGFBP-1 concentration is inversely correlated with insulin and the objective is to examine whether metabolic disturbances (diabetes, hypoglycaemia, gastrointestinal tumour) affect IGFBP-1 phosphorylation pattern. AS IGFBP-1 intereacts with alpha2 macroglobulin, the intention is to investigate the influence of disorders on this association. IGFBP-3 is glycoprotein and appears in several glycoforms. Different glycoforms having altered affinity for IGFs may appear due to metabolic disturbances, which we intend to study. IGFBP-3 binds to transferrin (Tf) and we intend to analyse samples with different ratio IGFBP-3 : Tf and different Tf saturation. The plan is to study the type and sugar content of glycans attached to IGF-Rs and their influence on ligand binding. Placenta from healthy and diabetic women will be used as a source of receptors. The binding of IGFs to receptors triggers pathways which may initiate tumour growth, thus, we will analyse glycans of IGF-Rs isolated from gastrointestinal tumours.