Title: 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 (2011-)
Funding: Ministry of Education, Science and Technological Development of the Republic of Serbia
Realization by: Institute for the Application of Nuclear Energy, University of Belgrade
Project leader: Olgica Nedić, PhD, Principal Research Fellow, INEP
Subject and description: Examination of structural characteristics of the IGF biniding proteins (IGFBP) and receptors (IGF-R), and their ability to form complexes. Structure of these molecules is modified by post-translational processes such as proteolysis, glycosylation, phosphorylation, oxidation and polimerisation, and the factors which affect these modifications are nutrition, physical activity, ageing, metabolical and other disorders. The project is divided into several topics, each covering one specific IGFBP or IGF-R.
1. There is a direct negative feedback control between the concentration of IGFBP-1 and the level of insulin in healthy people, whereas in persons with impaired glucose metabolism that feedback loop is very often lost. The influence of insulin and nutrition on the changes in the IGFBP-1 structure (monomer, multimer, fragment, complexes) and its reactivity (due to altered phosphorylation, oxidation, polimerisation and proteolysis) is investigated in metabolic disorders (diabetes, hypoglycemia) and in conditions with altered utilisation of glucose (such as intensive physical activity). IGFBP-1 interacts with α2 macroglobulin, which protects IGFBP-1 from proteolysis, so the influence of a disease on this interaction is also studied. A specific research topic includes investigation of the interaction between IGFBP-1 and fibrinogen.
2. IGFBP-2 exists in several molecular forms (complexes with α2 macroglobulin, momomer and fragments). In different (patho)physiological conditions (such as aging, cancer), the concentration of IGFBP-2 changes and also the relative presence of the molecular forms. We investigate factors which influence distribution of IGFBP-2 forms, and the possible importance of a specific molecular distribution in specific metabolic condition.
3. IGFBP-3 is the most abundant binding protein in the circulation, interacting with 70-75 % of the IGFs. It posseses several binding domains enabling its interaction with other molecules, especially with proteins. One of them is transferrin, the major transpoter of iron ions in the organism. The importance of iron ion in the formation of IGFBP-3/transferrin complexes has been under investigation, as well as the involvement of these complexes in the metabolism of iron (in healthy people and in persons with anemia or very high level of iron). The connection between complexes and tumors is being also investigated, as it is known that IGFBP-3 is a pro-apoptotic agent (for example in colorectal cancer).
4. IGF receptors, similarly to insulin receptor, are highly glycosilated and their glycan moiety can reach up to 25 % of the receptor mass. These receptors are important for physiological growth, as well as for tumor growth. The type and content of N-glycans attached to receptors isolated from placental membranes of different gestational ages, as well as from mothers diagnosed with preeclampsia and diabetes mellitus, are being investigated. The type and the content of N-glycans present on receptors isolated from tumor tissue are investigated as well.
Olgica Nedić, PhD in Biochemistry, Principal Research Fellow, Head of Department for Metabolism, Project leader, email@example.com
Dragana Robajac, PhD in Biochemistry, Research Associate, firstname.lastname@example.org
Goran Miljuš, PhD in Biochemistry, Research Associate, email@example.com
Miloš Šunderić, PhD in Biochemistry, Research Associate, firstname.lastname@example.org
Zorana Dobrijević, PhD in Biology, Research Associate, email@example.com
Nikola Gligorijević, PhD in Biochemistry, Research Associate, firstname.lastname@example.org
Ana Penezić, biochemist, Research Assistant, email@example.com