Lanosterol 14alpha-demethylase in biosynthesis of cholesterol and signalling sterols

Code

J1-6713 (C) - included in ARIS records

Head

PhD Damjana Rozman

Period

7/1/2004 - 6/30/2007

Range in 2007

0.41 FTE

Science

Natural sciences and mathematics (6)
Medical sciences (2)
Biotechnical sciences (4)

Reseacher status

Researcher (11)
Junior expert or technical associate (1)

Education

Doctor's degree (11)
Other (1)

Sex

Woman (6)
Man (6)

Status

Employed at RO and RRD (10)
No data on employment in RO (2)

No. of publications

0 (1)
10–99 (3)
100–999 (8)

Projects / Programmes source: ARIS

source: ARIS

Lanosterol 14alpha-demethylase in biosynthesis of cholesterol and signalling sterols

Research activity

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
P320	Natural sciences and mathematics	Nucleic acids, protein synthesis
P340	Natural sciences and mathematics	Lipids, steroids, membranes

Keywords

lanosterol 14alpha-demethylase, cytochrome P450, gene expression and regulation, transcriptome analysis, DNA chip technology, functional genomics, cholesterol biosynthesis, MAS sterols

Evaluation (rules)

source: COBISS

Evaluation of bibliographic research performance indicators according to ARIS methodology

Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases

source: WoS

source: Scopus

source: COBISS

Researchers (12)

no.	Code	Name and surname	Research area	Role	Period	No. of publicationsNo. of publications
1.	17572	PhD Marko Cotman	Veterinarian medicine	Researcher	2004 - 2007	119
2.	18622	PhD Nataša Debeljak	Biochemistry and molecular biology	Researcher	2004 - 2007	241
3.	18992	PhD Martina Fink	Biochemistry and molecular biology	Researcher	2004 - 2007	124
4.	20347	PhD Klementina Fon Tacer	Metabolic and hormonal disorders	Junior researcher	2004 - 2005	126
5.	12449	PhD Robert Frangež	Veterinarian medicine	Researcher	2004 - 2007	280
6.	24348	PhD Neža Grgurevič	Veterinarian medicine	Junior researcher	2004 - 2007	58
7.	24562	Helena Klavžar	Biochemistry and molecular biology	Technical associate	2004 - 2007	0
8.	18355	PhD Drago Kuzman	Physics	Researcher	2004 - 2007	64
9.	13330	PhD Gregor Majdič	Veterinarian medicine	Researcher	2004 - 2007	577
10.	22459	PhD Tadeja Režen	Neurobiology	Junior researcher	2004 - 2007	235
11.	06013	PhD Damjana Rozman	Biochemistry and molecular biology	Head	2004 - 2007	887
12.	24289	PhD Matej Seliškar	Biochemistry and molecular biology	Junior researcher	2004 - 2007	25

Organisations (3)

no.	Code	Research organisation	City	Registration number	No. of publicationsNo. of publications
1.	0258	Lek Pharmaceutical Company d.d.	Ljubljana	1732811	8,438
2.	0381	University of Ljubljana, Faculty of Medicine	Ljubljana	1627066	48,238
3.	0406	University of Ljubljana, Veterinary Faculty	Ljubljana	1627139	10,777

Abstract

Disturbed cholesterol homeostasis leads to hyperlipidemias that represent one of the major causes of death in developed societies. The preceeding project contributed importantly to understanding the tissue-specific mechanisms of cholesterol and meiosis activating sterol (MAS) synthesis, at the level of gene regulation (trans-activation of lanosterol 14alpha demethylase CYP51 in sterol-repressed conditions), protein expression (CYP51 enzymatic activity in acrosomal membranes of sperm) and intracellular transport (traffick from ER through the Golgi to the acrosome). The vision of this project is to translate the knowledge of the multi-level regulation of CYP51 to other genes of cholesterol homeostasis (the STEROLTALK group), by applying functional genomic tools in studies of the cross-talk of cholesterol homeostasis with endogenous and exogenous pathways. Due to a high evolutionarily conservation of cholesterol synthesis and metabolism in mammals, several animal models will be applied, from mouse (in vivo studies) to big mammals (bull and ram), in addition to human immortal cell lines. Regulation of cholesterogenic genes will be studied, with particular emphasis on tissue-sepcificity and signalling pathways, that interact with the cholesterol feedback loop. By applying expression profiling by DNA chips and real time PCR and promoter studies, the physiological and patophysiological conditions that allow a cholesterol-feedback independent expression will be identified. The amount of cholesterol and MAS will be measured in animal tissues and cell cultures where different signalling pathways will be activated. Methods for proteome studies will be applied to determine the composition of CYP51 protein compelxes in Golgi and on the acrosome. The CYP51 enzyme activity will be measured in different subcellular fractions and the intracellular transport of CYP51-GFP-fusion protein evaluated by confocal microscopy. Factors that prevent the homologous recombination of the cyp51-lox P constructs into the mouse genome will be determined and new recombination constructs prepared, contributing to the assession of the final goal - a cyp51 conditional knockout mouse by the Cre-loxP technology.