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Grant: Operating Grant

Université du Québec à Montréal

$450,928.00

Characterization and functional analyses of incorporated HERV envelope proteins in placenta-derived exosomes

FY 2012-13

Summary
Human endogenous Viruses (HERVs) are sequences having been conserved over millions of years in our genome and produce proteins originating from former viruses. Some of these proteins are important for the normal development of the placenta. Changes in the level of these proteins in pregnant women suffering from pre eclampsia have been associated with this disorder. Recently, our team has shown that these proteins can also be present at the surface of extracellular entities known as exosomes, which have been described to play a functional role in different cell types and tissues. Herein, we are hypothesizing that these former viral proteins are important for the normal development of the placenta through their presence not only at the surface of placental cells but also at the surface of exosomes and that they differ in abundance on the surface of exosomes from preeclamptic patients. To test this, we will demonstrate that some of these proteins are indeed varying in their levels on exosomes derived from placental cells from normal pregnant women vs patients. Next, we will determine if these proteins are involved in processes associated with exosome function, such as binding and fusion with adjacent cells or inhibition of activation of cells from the immune system. We will also test if their altered levels in exosome from pre-eclamptic patients result in changes in exosome function. The body of knowledge gained from these studies will permit to achieve a better understanding of the involvement of these HERV proteins through their association with exosomes on the function of the placenta. Furthermore, they will allow us to determine if reduction of these proteins in pre-eclamptic (PE) patients leads to altered exosome function. Finally, this project might provide indication that HERV proteins could become new and promising markers for the development of PE.
Program
Operating Grant
Location
Quebec, Canada
Recipient Type
Academia
Type
Grant
Source
CIHR Funding Decisions Database

As published

Id
281657
Name
Barbeau Benoit
Region
Québec
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Human Development, Child and Youth Health
Theme2
Biomedical
Prcname2
Clinical Investigation - A: Reproduction, Maternal, Child and Youth Health
Projecttitle
Characterization and functional analyses of incorporated HERV envelope proteins in placenta-derived exosomes
Programtype2
Operating Grants
Orgnameinp2
Université du Québec à Montréal
Cihramount2
$450,928
Cihrequipment2
$0
Programname2
Operating Grant
Keyworddelim
Biomarkers; Cellular Binding; Envv And Envp(B); Exosomes; Human Endogenous Retroviruses; Human Trophoblasts; Immunosuppression; Placenta; Pre-Eclampsia; Syncytin-1 And Syncytin-2; Uptake And Fusion
Abstract
Human endogenous Viruses (HERVs) are sequences having been conserved over millions of years in our genome and produce proteins originating from former viruses. Some of these proteins are important for the normal development of the placenta. Changes in the level of these proteins in pregnant women suffering from pre eclampsia have been associated with this disorder. Recently, our team has shown that these proteins can also be present at the surface of extracellular entities known as exosomes, which have been described to play a functional role in different cell types and tissues. Herein, we are hypothesizing that these former viral proteins are important for the normal development of the placenta through their presence not only at the surface of placental cells but also at the surface of exosomes and that they differ in abundance on the surface of exosomes from preeclamptic patients. To test this, we will demonstrate that some of these proteins are indeed varying in their levels on exosomes derived from placental cells from normal pregnant women vs patients. Next, we will determine if these proteins are involved in processes associated with exosome function, such as binding and fusion with adjacent cells or inhibition of activation of cells from the immune system. We will also test if their altered levels in exosome from pre-eclamptic patients result in changes in exosome function. The body of knowledge gained from these studies will permit to achieve a better understanding of the involvement of these HERV proteins through their association with exosomes on the function of the placenta. Furthermore, they will allow us to determine if reduction of these proteins in pre-eclamptic (PE) patients leads to altered exosome function. Finally, this project might provide indication that HERV proteins could become new and promising markers for the development of PE.
Competitiondate
201303
Approvedterm2
4 yrs 0 mth
Pinamesdelim
Barbeau, Benoit
Approvedterm
4 ans 0 mois
Cihrcontribution2
~ $450,928~ $0~
Université du Québec à Montréal - $450,928 Grant (201… | Canada Spends