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Projects / Programmes source: ARIS

Molecular mechanism of novel hypolipidemics

Research activity

Code Science Field Subfield
1.09.00  Natural sciences and mathematics  Pharmacy   

Code Science Field
T410  Technological sciences  Pharmaceuticals and related technologies 
Keywords
cholesterol, potential hypolipidemics, target validation, molecular mode of action, transcriptome analysis, siRNA, sterol profiling, bioinformatics
Evaluation (rules)
source: COBISS
Researchers (11)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  28452  PhD Juan Antonio Contreras  Biochemistry and molecular biology  Researcher  2007 - 2008  58 
2.  20347  PhD Klementina Fon Tacer  Metabolic and hormonal disorders  Researcher  2008  126 
3.  09905  PhD Darko Kocjan  Chemistry  Researcher  2007 - 2008  167 
4.  24392  PhD Katja Kristan  Pharmacy  Researcher  2007 - 2008  95 
5.  18355  PhD Drago Kuzman  Physics  Researcher  2007 - 2008  64 
6.  24465  PhD Luka Peternel  Cardiovascular system  Researcher  2007 - 2008  49 
7.  28382  PhD Uršula Prosenc Zmrzljak  Public health (occupational safety)  Junior researcher  2007 - 2008  89 
8.  22459  PhD Tadeja Režen  Neurobiology  Researcher  2007 - 2008  235 
9.  06013  PhD Damjana Rozman  Biochemistry and molecular biology  Researcher  2007 - 2008  887 
10.  24289  PhD Matej Seliškar  Biochemistry and molecular biology  Researcher  2007 - 2008  25 
11.  01878  PhD Uroš Urleb  Pharmacy  Head  2007 - 2008  380 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0258  Lek Pharmaceutical Company d.d.  Ljubljana  1732811  8,437 
2.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,236 
Abstract
The molecular mechanisms of novel cholesterol biosynthesis inhibitors will be studied on molecular level. For a difference with statins, which inhibitHMG CoA reductase in the early part of sterol biosynthesis path, novel derivatives inhibit enzymes in the later part and thereby do not influence the biosynthesis of some important intermediates of previous phases. The novel compounds will be tested ex vivo on a set of immortal cell lines of human hepatocytes with suppressed expression of individual gene in biosynthesis. The selected genes will be suppressed with siRNA method. Besides, compounds will be tested in in vivo conditions on hypercholesterolemic mice and genetically transformed yeast, which instead of yeast sterols synthesize human cholesterol. The acquired samples will be appointed the global profile of gene expression by using DNA microarrays and sterol profiling with HPLC and radio-detector. On the basis of analysis of performed measurements, a hypothesis of molecular action of novel compounds on molecular level will be formulated. The hypothesis will be verified by measurements of new compound inhibitory coefficient on a selected target enzyme. On the basis of confirmed hypothesis on compound action, further optimization of inhibitory compound properties will be possible by molecular modelling of enzyme - compound interactions.
Significance for science
Novel molecular targets and discovery of novel inhibitors of cholesterol biosynthesis are importan result for pharmaceutical science and important foo the unmet medical needs. Results of genomic analyses gave more deep insight into profile of activity of novel inhibitors as well into biological signaling pathways.
Significance for the country
Introduction of new research areas, new scientific discoveries and technological advancement, networking of industrial and academic reserch groups, novel reserchers finishing PhD degree
Most important scientific results Final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Final report, complete report on dLib.si
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