Complex diseases as a model system for phenotype modulation – structural and functional analysis of molecular biomarkers

Principal Investigator: Dragica Radojkovic, PhD

Phenotype results from complex interactions among numerous players, and each qualitative and/or quantitative change in gene expression could lead to phenotype modulation. Molecular biomarkers identified in our previous research as phenotype modulators, as well as the novel ones discovered in the frame of the project, will be analyzed on structural and functional level in the following model systems: cardiovascular diseases, pulmonary diseases and solid tumors. The majority of selected molecular markers participate in regulation of hemostasis, inflammatory processes, tissue remodeling, common signal pathways, cellular proliferation and protection from oxidative stress. In this project the following structural genomic elements will be studied: origins of replication (ori), 5' and 3' gene regulatory regions, gene sequences, as well as the elements important for posttranscriptional and post translation modification. Functional analysis will be performed both at the nucleic acid and protein level in selected cell lines and primary cell cultures. We also plan to standardize the conditions to introduce zebra fish (Danio rerio) animal model system for study of cardiovascular phenotype as well as to introducing confocal microscopy for monitoring molecular effects and „fate„ of investigated biomarkers. The final aim is to determine single and combined modulator effects of studied biomarkers on phenotype, with possible application in diagnostics and follow up of diseases under study.