Projects / Programmes
Functional genomics of the complex regulatory network of cholesterol homeostasis
| Code |
Science |
Field |
Subfield |
| 1.05.00 |
Natural sciences and mathematics |
Biochemistry and molecular biology |
|
| Code |
Science |
Field |
| P004 |
Natural sciences and mathematics |
Biochemistry, Metabolism |
| P340 |
Natural sciences and mathematics |
Lipids, steroids, membranes |
| P170 |
Natural sciences and mathematics |
Computer science, numerical analysis, systems, control |
| P176 |
Natural sciences and mathematics |
Artificial intelligence |
| B110 |
Biomedical sciences |
Bioinformatics, medical informatics, biomathematics biometrics |
cholesterol homeostasis, drug metabolism, circadian regulation, DNA microarray, gene regulatory network, bioinformatics
Researchers (11)
Organisations (2)
Abstract
The STEROLTALK v2 microarray containing over 300 mouse and human genes involved in cholesterol synthesis and metabolism, the nuclear receptor-meduated signalling pathways, circadian regulation and drug metabolism, has been developed within the FP6 EU project (No. 512096) in July 2006. In the proposed project with the acronym CHOLNET, we will use this microarray, together with other Steroltalk tools, to dechipher the complex transcriptional regulatory network of cholesterol homeostasis, drug metabolism and the circadian regulation The mouse models will be applied (drug-treated normal and hyperlipidemic mice and CREM knockout mice), together with primary human hepatocytes (source of RNA from the Hungarian collaborator), apporaches of machine learning as well as computer and mathematical modelling. For circadian experiments the mouse liver samples will be collected in 4h intervals over 1-2 days. Transcriptional regulatory networks will be assessed through integrative analysis of the Steroltalk transcriptome and will be upgraded by the available information of corresponding proteins and the sterol metabolome. This will allow for the first time to decipher the multi-level response of cholesterol homeostasis to known and candidate drugs, and its circadian modulation, by monitoring the modulated responses of genes, and upgrading this by knowledge about proteins and sterol metabolites. Deposited analytical data will be evaluated by different bioinformatic approaches, to assist in building relevant mathematical models with predictive power, ready for implementation in understanding and treating the hyperlipidemia-based diseases. This project will contribute to the Steroltalk efforts to advance our understanding of the cross talk of cholesterol homeostasis with drug metabolism and the circadian regulation.
Significance for science
Discovery of Novel Scientific Findings. Disorders in cholesterol homeostasis are one of the main factors in the development of hyperlipidemias and origin of cardio-vascular diseases. By applying global approaches (DNA chip technology), molecular mechanisms and cross-talks will be assesed, thereby importantly contributing to a global understanding of cholesterol homeostasis and its cross-talks. Our basic research attained international recognition, which is evident from the list of publications and the citation index.
Improving and Enlarging Methology Tools. We introduced the DNA chip technology into the Slovenian research sphere, and together with other consortium members and partners from industry also provided the necessary infrastructure.
Development of Own Basic Research. Scientific findings stated above belong to the category of fundamental scientific findings in the field of biochemistry and molecular biology as well as functional genomics. Publications of the last years of the previous project are the result of own basic research in cooperation with international partners.
Development of Other Fundamental Sciences. The proposed project is explicitly of interdisciplinary character. The newest tools of functional genomics are applied, and besides offering fundamental knowledge in the basic field of biochemistry and molecular biology it also reaches into the domain of bioinformatics and mathematical modeling. It is expected that investigations planned in present project will exert an influence on all three fields stated.
Development of Applicative Research. Searching for new hypolipidemics with the aim of lowering the cholesterol level remains a commercially interesting field of pharmaceutical industry. The previous project resulted in permanent cooperation with the pharmaceutical company Lek, who implement the basic findings of our research. Lek is also a partner in the proposed project.
Development of New Technologies. The proposed research will contribute to further development of DNA microarray technology in Slovenia.
Significance for the country
Many human diseases are caused by disturbances of homeostasis. The project “Functional genomics of the complex regulatory network of cholesterol homeostasis« (CHOLNET) proposes an innovative research focused on integrating post-genomic research by studying the complex regulatory network of drug-disturbed cholesterol homeostasis, that is also under the circadian control. It links research in functional genomics with biomedical and biotechnological approaches, with the aim to contribute to improved human health in Slovenia and in the world.
The project CHOLNET is performed within the Centre for Functional Genomics and Bio-Chips. CFGBC is a consortium based research and education institution of a Slovenian national importance, that resides at the Faculty of Medicine UL and also within the Network of Research and Infrastructure Centres of University of Ljubljana. Researchers of CHOLNET that perform transcriptome and bioinformatic analyses and data mining approaches for the above project, consult or act as tutors also for several other projects that are performed within CFGBC. With these activities the project CHOLNET importantly contributes to education of Slovenian researchers in the field of functional genomics and microarray technologies, to fulfill the needs of pharmaceutical industry and clinical institutions.
Most important scientific results
Annual report
2008,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
final report,
complete report on dLib.si
