Karakterizacija preuređivanja endosomalnih membranatijekom rane faze infekcije mišjim citomegalovirusom koje vodi k formiranju kompleksa za stvaranje viriona

Opis projekta
Beta-herpesviruses massively reorganize the intracellular compartments in order to create an environment for virion production, known as assembly complex (AC). This structure develops gradually from the earliest stages of infection and involves stepwise reorganization of membrane organelles. Although the final structure is relatively well characterized during human cytomegalovirus infection, the sequence of events that leads to the development of the AC is poorly understood. The goal of this project is to characterize processes proceeding to the formation of the AC in cells infected with murine CMV (MCMV). MCMV starts with remodeling of the endosomal system very early in the infection, which we characterized as development of the early-phase endosomal retention compartment (EPERC). There is strong indication that the EPERC is predecessor of AC. It is generally accepted that endosomal remodeling is driven by small GTPases from the Rab and Arf family and phosphoinositides (PI). In the proposed project, we plan to reveal sequence of membranous organelle reorganization events in the early phase of infection that presumably lead to the formation of the AC. With that purpose, we will determine the role of small GTPases of the Rab and Arf family and their effector proteins in membrane organelle perturbation events during the early phase of MCMV infection. Finally, we plan to characterize membrane domains of the EPERC during the entire early phase regarding PI content, which include the study of PI effectors and major enzymes that drive PI conversion and thereby change membrane identity. To achieve these goals, we will use triple immunofluorescence staining of EPERC, genetically engineered fluorescent probes, RNA silencing and pharmacological inhibitors. Outcome of the proposed research will be a reconstruction of the mechanism of development of the EPERC and identification of cellular proteins that are targeted by MCMV in the early phase of infection.

Akronim
AsCo

Šifra projekta
IP-2014-09-9564

Poziv
2014-09

Vrsta projekta
Znanstveno-istraživački

Vrsta financiranja
Kompetitivno projektno financiranje

Financijer
HRZZ - Hrvatska zaklada za znanost

Detalji financiranja
 IP - Istraživački projekti

Ukupan iznos financiranja projekta
796.636,00 HRK

Trajanje projekta
2015-09-01 - 2019-01-09

Ustanova - uloga
Medicinski fakultet, Rijeka - Koordinator aktivnosti (796.636,00 HRK)

Osoba - Ustanova - uloga [pocetak - zavrsetak]
Pero Lučin (MBZ: 142314, CROSBI: 12677) - Medicinski fakultet, Rijeka - Voditelj projekta [2015-09-01 - 2019-01-09]
Hana Mahmutefendić Lučin (MBZ: 247686, CROSBI: 35099) - Medicinski fakultet, Rijeka - Suradnik [2015-09-01 - 2019-01-09]
Gordana Blagojević Zagorac (MBZ: 259873, CROSBI: 31041) - Medicinski fakultet, Rijeka - Suradnik [2015-09-01 - 2019-01-09]
Marina Marcelić (MBZ: 374902, CROSBI: 35537) - Medicinski fakultet, Rijeka - Suradnik [2015-09-01 - 2019-01-09]
Ljerka Karleuša (MBZ: 334545, CROSBI: 10966) - Medicinski fakultet, Rijeka - Suradnik [2015-09-01 - 2019-01-09]
Silvija Lukanović Jurić (MBZ: 354540, CROSBI: 33380) - Medicinski fakultet, Rijeka - Suradnik [2015-09-01 - 2019-01-09]
Kristina Grabušić (MBZ: 270241, CROSBI: 22540) - Medicinski fakultet, Rijeka - Suradnik [2015-09-01 - 2019-01-09]