Involvement of Kinases Sch9, Pkh1 and PKA in Start-up of Growth in S. cerevisiae

Ines Cottignie
In deze masterthesis werd het mechanisme achter de start van celgroei bestudeerd in gist via fundamenteel biologisch onderzoek. Kinasen, een bepaald type eiwitten, lijken betrokken te zijn bij het linken van celgroei met de beschikbaarheid van voeding.

Wat de cel gemeen heeft met een jukebox

Geen muntje geworpen in de jukebox? Geen muziek! De jukebox is in rust-modus, er branden enkel een paar aanlokkelijke lichtjes. Werpt u een muntje in de jukebox? Na een reeks reacties klinkt uiteindelijk muziek.

U zou het niet verwachten, maar er zijn zekere gelijkenissen tussen de jukebox en de wondere wereld binnenin de cel. Beeld u even in: een jukebox is een cel, een muntje is voedsel. In een jukebox is muziek een actie die volgt op de aanwezigheid van het muntje. In de cel is celgroei de actie die volgt op de aanwezigheid van voedsel. Cellen stoppen met groeien wanneer er een tekort is aan voedsel, zoals de rust-modus van een jukebox omdat er geen muntje meer ingeworpen werd. Is voeding opnieuw aanwezig, dan zullen cellen ontwaken uit hun rust-modus na een reeks van reacties. Ze starten opnieuw met hun groei. Dit geldt voor alle soorten cellen, van bacteriële tot menselijke. Zo is het ook in alle soorten jukeboxen: het muntje leidt tot muziek.

Wat ik nu al heb verteld over de regulatie van celgroei is algemeen geweten. Wat de achterliggende processen zijn, is echter nog steeds een groot mysterie. Het doel van deze scriptie was dan ook de waarheid achter het mysterie van de regulatie van celgroei helpen ontrafelen via fundamenteel biologisch onderzoek.

Allemaal wel boeiend, maar wat heeft fundamenteel onderzoek voor nut?

Ik zie u wel denken hoor. Luister, er kunnen belangrijke toepassingen voortvloeien uit dit soort onderzoek. In bepaalde ziektes bijvoorbeeld is er een grote chaos in de organisatie van de groei. Denk maar aan kanker en diabetes, u kent vast wel iemand met zo’n ziekte. Hoe meer geweten is over de basisprocessen van cellen, hoe beter alles weer in goede banen geleid kan worden met behulp van voeding of medicijnen.

Gist met fluorescente eiwitten onder de loep

Om deze basisprocessen te bestuderen, werd in deze scriptie Saccharomyces cerevisiae gebruikt. Wat? Tja, wetenschappers maken het graag moeilijk. Synoniemen zijn bakkersgist of brouwersgist. Goed gezien, dit micro-organisme wordt ook gebruikt bij het bakken van brood en het brouwen van bier. Werken met dit micro-organisme heeft veel voordelen voor onderzoekers. Het is praktisch in gebruik, het is niet gevaarlijk en heeft meer gemeenschappelijk met de menselijke cel dan u zou denken. Ook moeten minder dieren afzien als bij de proeven eerst gist wordt gebruikt.

In teken van dit onderzoek werden eiwitten onderzocht in gist. Eiwitten zijn niet enkel aanwezig in lekkere proteïnerepen, maar overal in uw lichaam. Ze zijn nodig voor bijna alle taken in de cel. Sommige eiwitten geven vorm aan de cel, anderen helpen in de organisatie. Zo zijn er ook eiwitten die veranderingen in de buitenwereld waarnemen en ervoor zorgen dat de cel er zich kan aan aanpassen. Zoals u wel zou kunnen begrijpen, zijn eiwitten levensnoodzakelijk. Wat u hierbij ook moet weten, is dat een eiwit nooit alleen werkt om iets te realiseren. Er is altijd een samenwerking tussen eiwitten door middel van interacties.

Twee geavanceerde technieken werden in deze scriptie gebruikt om de aanwezigheid van interacties tussen eiwitten te achterhalen. De eerste techniek was ‘GST-pull-down’. Eiwitinteracties worden er onderzocht na het verwijderen van de eiwitten uit de cellen. Er wordt getest of eiwitten al dan niet binden aan elkaar. De tweede techniek was de ‘split-citrine-BiFC’. Hier worden eventuele eiwitinteracties zichtbaar gemaakt binnenin de levende cel met behulp van de fluorescentiemicroscoop. Gistcellen worden op zo’n manier gemaakt dat wetenschappers fluorescentie kunnen zien wanneer de twee eiwitten die ons interesseren samenkomen.

Naast het bestuderen van eiwitinteracties werd de locatie van bepaalde eiwitten in levende gistcellen bestudeerd om informatie te bekomen. Dit was mogelijk door het maken van cellen met een fluorescent eiwit met daaraan het eiwit dat ons interesseert. De plaats in de cel waar de fluorescentie te zien is, is ook de plaats waar het eiwit zich bevindt.

Samenwerkende eiwitten

In deze scriptie werd mogelijks aangetoond dat het eiwit ‘Gap1’ een interactie heeft met de eiwitten ‘Sch9’, ‘Pkh1’ en ‘Tpk1’. Klinkt als Chinees voor u? Da’s normaal, ik haal er even de jukebox bij. ‘Gap1’ kan u zien als de gleuf voor de muntjes van een jukebox, want het laat het voedsel binnen en start een reeks reacties. ‘Gap1’ is een eiwit dat de bouwstenen van eiwitten (specifiek soort voeding) in de buitenwereld kan transporteren in de cel. ‘Gap1’ laat dan ook weten aan de cel dat er voeding aanwezig is in de buitenwereld. De eiwitten ‘Sch9’, ‘Pkh1’ en ‘Tpk1’ zijn kinasen. Deze kunnen gezien worden als het mechanisme binnenin een jukebox. Het zijn eiwitten die op een specifieke manier de actie van andere eiwitten kunnen beïnvloeden. Een interactie van ‘Gap1’ met ‘Sch9’, ‘Pkh1’ en ‘Tpk1’ kan u dus zien als de samenwerking tussen de muntgleuf en het mechanisme van de jukebox.

Nog meer resultaten! Er werden ook indicaties gevonden voor interacties tussen eiwitten ‘Gcd1’ en/of ‘Gcd6’ met diezelfde kinasen ‘Sch9’, ‘Pkh1’ en ‘Tpk1’. ‘Gcd1’ en ‘Gcd6’ mag u voorstellen als de naald van de platenspeler in een jukebox. Het zijn eiwitten die de cel helpen bij het starten van het proces van het aanmaken van nieuwe eiwitten. Dit zorgt uiteindelijk voor de groei van de cel.

Missie twee keer geslaagd

Al deze resultaten speculeren dat er een link is tussen de gewaarwording van veranderingen in de buitenwereld in de hoeveelheid bouwstenen van eiwitten -de voeding of analoog het muntje- via ‘Gap1’. Deze zal de informatie communiceren in de cel via de kinasen -of analoog het mechanisme in de jukebox-. Dit leidt uiteindelijk tot de start van de groei van de cel via ‘Gcd1’ en ‘Gcd6’, de naald van de platenspeler die zorgt voor muziek in een jukebox. Missie onderzoek geslaagd!

U heeft zich zojuist geworsteld door de thesis ‘Involvement of Kinases Sch9, Pkh1 and PKA in Start-up of Growth in S. cerevisiae’. Proficiat! Met deze titel was u niet aan de tekst begonnen zeker? U weet nu wat voor bijzondere dingen onder andere gedaan worden door mensen met labojassen. Missie wetenschapscommunicatie geslaagd!

 

 

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Universiteit of Hogeschool
Biologie afstudeerrichting moleculaire celbiologie
Publicatiejaar
2016
Promotor(en)
Johan Thevelein
Kernwoorden
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