The role of DISP3 protein in lipid metabolism
Project goals
In the body the brain is the most cholesterol rich organ. Despite this, remarkably little is known about the mechanisms in the brain that regulate cholesterol homeostasis. By screening for T3 regulated genes we have identified Disp3, a sterol-sensing domain containing protein. DISP3 localizes within the endoplasmic reticulum and was further found to co-localize with cholesterol. Ectopic expression of DISP3 in fibroblasts resulted in elevated cholesterol levels combined with an altered cholesterol distribution. Currently, it is unknown what is responsible for the alteration of cholesterol in cells with modulated DISP3 expression and whether this protein interacts directly with cholesterol or other lipids. During the proposed project we will attempt to further characterize the function of DISP3 with regards to the regulation of cholesterol homeostasis and to study the potential physical interaction between DISP3 and cholesterol by in vitro and in vivo methods. In addition, we will establish the importance of the sterol-sensing domain for modulating cellular cholesterol distribution.
Keywords
Public support
Provider
Czech Science Foundation
Programme
Standard projects
Call for proposals
Standardní projekty 15 (SGA02012GA-ST)
Main participants
Ústav molekulární genetiky AV ČR, v. v. i.
Contest type
VS - Public tender
Contract ID
P301-12-1478
Alternative language
Project name in Czech
Úloha proteinu DISP3 v lipidovém metabolismu
Annotation in Czech
Přestože mozek obsahuje značné množství cholesterolu, je poměrně málo známo o mechanismech jeho regulace v tomto orgánu. Při hledání nových genů, které jsou regulovány thyroidním hormonem jsme identifikovali Disp3, nového člena SSD (sterol-sensing domain) proteinové rodiny. Vnitrobuněčně se DISP3 nachází v oblasti endoplazmatického retikula, kde kolokalizuje s cholesterolem. Ektopická exprese DISP3 ve fibroblastech vede k relokalizaci a k akumulaci celkového cholesterolu v buňce. V současné době není známo co způsobuje změnu cholesterolu v buňkách s modulovanou expresí DISP3 a zda DISP3 interaguje přímo s cholesterolem či s jinými lipidy. V předkládaném projektu chceme dále charakterizovat funkci DISP3 v homeostáze buněčného cholesterolu a dále pak studovat přímou interakci mezi DISP3 proteinem a cholesterolem, popřípadě dalšími steroly, a to pomocí in vitro a in vivo metod. Dále bychom rádi objasnili úlohu SSD-domény, popřípadě dalších domén, v této interakci.
Scientific branches
R&D category
ZV - Basic research
CEP classification - main branch
FB - Endocrinology, diabetology, metabolism, nutrition
CEP - secondary branch
CE - Biochemistry
CEP - another secondary branch
EB - Genetics and molecular biology
10603 - Genetics and heredity (medical genetics to be 3)
10604 - Reproductive biology (medical aspects to be 3)
10605 - Developmental biology
10608 - Biochemistry and molecular biology
10609 - Biochemical research methods
30101 - Human genetics
30202 - Endocrinology and metabolism (including diabetes, hormones)
Completed project evaluation
Provider evaluation
U - Uspěl podle zadání (s publikovanými či patentovanými výsledky atd.)
Project results evaluation
The main goal of the project was to characterize function of DISP3, relevant in lipid metabolism and cholesterol levels. Investigators fulfilled the aims of the application and obtained results would enable further research, particularly in the field of oncogenetics. The project, which contributed to the education of the students, has resulted in three publications in sound journals (e.g. NPG).
Solution timeline
Realization period - beginning
Jan 1, 2012
Realization period - end
Apr 25, 2017
Project status
U - Finished project
Latest support payment
Mar 26, 2015
Data delivery to CEP
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data delivery code
CEP18-GA0-GA-U/02:1
Data delivery date
May 4, 2018
Finance
Total approved costs
7,448 thou. CZK
Public financial support
7,448 thou. CZK
Other public sources
0 thou. CZK
Non public and foreign sources
0 thou. CZK
Basic information
Recognised costs
7 448 CZK thou.
Public support
7 448 CZK thou.
100%
Provider
Czech Science Foundation
CEP
FB - Endocrinology, diabetology, metabolism, nutrition
Solution period
01. 01. 2012 - 25. 04. 2017