Title Investigating co-aggregation of EHD3 and its potential role in chronic mental illnesses
Title (croatian) Istraživanje koagregacije EHD3 i njegove potencijalne uloge u kroničnim mentalnim bolestima
Author Tina Fartek
Mentor Nicholas James Bradshaw (mentor)
Committee member Rozi Andretić Waldowski (predsjednik povjerenstva)
Committee member Antonija Jurak Begonja (član povjerenstva)
Committee member Nicholas James Bradshaw (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2020-09-22, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology Molecular Biotechnology
Abstract Chronic mental illnesses (CMI) affect people’s daily lives including their thinking, functioning and emotions. These include schizophrenia, bipolar disorder and major depressive disorder, and are characterized by their perpetual and recurrent nature. There has therefore been a need to identify possible biological targets to get a deeper understanding of mental illnesses and to improve treatment and diagnosis standards. One newly studied concept is protein aggregation as a possible non-genetic cause of chronic mental illnesses. Five proteins were previously discovered to aggregate in brains of patients with CMI. Some of these have been confirmed to aggregate on their own, with a suggestion that each of them might influence the representation of a specific subtype of previously mentioned chronic mental illnesses. However, there have also been instances of co-aggregation in which case one protein stimulates the other one to aggregate. Co-aggregation represents the possibility that some or all of these proteins may interact with each other as a part of a single aggregation syndrome.
EHD3 is a newly discovered aggregating protein in mental illness, a member of the EHD protein family, encoded by the EH domain-containing 3 gene. While there is not a lot known about its functions, it is believed to be one of the key regulators of endocytic transport and involved in promotion of dopaminergic transmission. In this research, we investigated the aggregation properties of EHD3 and specifically possible co-aggregation of EHD3 with TRIOBP-1 and Dysbindin 1A in mammalian cells. TRIOBP-1 is an aggregating protein involved in modulation of actin through binding to F-actin fibers, while Dysbindin 1A is involved in regulation of neurotransmitter release and brain development.
Fluorescent microscope results have shown that while EHD3 aggregated both alone and in the presence of the two proteins, there was no sign of co-aggregation. Future research should focus on investigating both whether EHD3 aggregates in cells with other proteins implicated in mental illnesses, but also on whether aggregation of EHD3 and these other proteins occurs in the same patients.
Abstract (croatian) Kronične mentalne bolesti utječu na svakodnevne živote ljudi, uključujući njihovo razmišljanje, funkcioniranje i osjećaje. Njima pripada shizofrenija, bipolarni poremećaj i klinička depresija, a karakterizira ih trajnost i ponovno javljanje. S obzirom na to, postoji potreba za pronalaskom mogućih bioloških meta kako bismo ostvarili dublje razumijevanje mentalnih bolesti i unaprijedili standarde dijagnoze i tretmana. Agregacija proteina kao mogući ne-genetski uzročnik kroničnih mentalnih bolesti jedan je od novije istraživanih pojmova u ovom području. Prethodno je otkriveno pet proteina koji agregiraju u takvim bolestima. Za neke od njih potvrđeno je da agregiraju samostalno, pri čemu svaki zasebno može utjecati na prezentaciju određenih podvrsta prethodno navedenih bolesti. Međutim, zabilježeni su i slučajevi kada jedan protein potiče drugog na agregiranje. Koagregacija predstavlja mogućnost da neki ili svi navedeni proteini međudjeluju zajedno kao dio agregacijskog sindroma.
EHD3 je novootkriveni agregirajući protein u mentalnim bolestima. Dio je proteinske obitelji EHD, a kodiran je od strane gena koji sadrži EH domenu 3. Iako se trenutno ne zna mnogo o njegovoj ulozi, smatra se da je jedan od ključnih regulatora endocitoznog prijenosa i da je uključen u promociju transmisije dopamina. U ovom istraživanju, ispitana su agregacijska svojstva EHD3 i potencijalna mogućnost koagregacije EHD3 s proteinima TRIOBP-1 i Dysbindin 1A u stanicama sisavaca. TRIOBP-1 je agregirajući protein uključen u modulaciju aktina vezanjem za F-aktinska vlakna; dok je Dysbindin 1A uključen u regulaciju otpuštanja neurotransmitera i razvoj mozga.
Rezultati fluorescentne mikroskopije pokazali su da, iako EHD3 agregira i samostalno i u prisustvu ova dva proteina, nema znakova koagregacije. Buduća istraživanja trebala bi ispitati agregira li EHD3 u stanicama s drugim proteinima povezanim s mentalnim bolestima, kao i pitanje odvija li se agregacija EHD3 i tih proteina kod istih pacijenata.
Keywords
protein aggregation
chronic mental illnesses
EHD3
Keywords (croatian)
agregiranje proteina
kronične mentalne bolesti
EHD3
Language english
URN:NBN urn:nbn:hr:193:621378
Project Number: IP-2018-01-9424 Title: Istraživanje shizofrenije kroz ekspresiju netopivih proteina Acronym: CandidIskren Leader: Nicholas Bradshaw Jurisdiction: Croatia Funder: HRZZ Funding stream: IP
Study programme Title: Biotechnology and drug research Study programme type: university Study level: undergraduate Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biotehnologije i istraživanja lijekova (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biotehnologije i istraživanja lijekova)
Type of resource Text
File origin Born digital
Access conditions Closed access
Terms of use
Created on 2020-09-24 10:08:47