Erstmals ist es Wissenschaftlern an der Uni Ulm gelungen, live zu beobachten, wie in Embryonalzellen eines Zebrabärblings die Transkription der DNA, beziehungsweise auf Deutsch DNS (Desoxyribonukleinsäure), ausgelöst wird. Das Ulmer Forscherteam aus Biophysikern, Biochemikern und Molekularbiologen beobachtete dabei die Biomoleküle sozusagen bei der Arbeit. Ihr faszinierendes Ergebnis: „Erst wenn es richtig eng wird im Zellkern, wird das Genom aktiviert“, so umschreibt Entwicklungsbiologe Professor Gilbert Weidinger vom Institut für Biochemie und Molekularbiologie den Befund.
ERGEBNISSE AUF DEN MENSCHEN ÜBERTRAGBAR
Die Untersuchungen wurden zwar in Embryonen des Zebrabärblings vorgenommen, doch Weidinger sowie sein Kollege, Christof Gebhardt vom Institut für Biophysik an der Universität Ulm, sind sich sicher: „Die am Zebrabärbling gewonnenen Erkenntnisse über den Zusammenhang zwischen Zellkernvolumen und Transkriptionsfaktoraktivität können dabei auf andere Spezies wie den Menschen übertragen werden.“
Basis der Untersuchung ist die DNA als Bauplan des Lebens. In ihr sind alle Informationen vorhanden, die der biologische Organismus für seine Entwicklung benötigt. Nutzbar wird diese genetisch codierte Information erst durch Übertragung der DNA in RNA beziehungsweise auf Deutsch in RNS (Ribonukleinsäure), eine Art Bauplan zur Synthese von Biomolekülen.
ZELLKERNVOLUMEN KOMMT SCHLÜSSELROLLE ZU
Unbekannt beim Transkriptionsprozess war bisher, wie die Genomaktivierung zum ersten Mal erfolgt: Da sich in den frühen Phasen der Embryonalentwicklung die Zellen teilen, ohne zu wachsen, wird das Volumen der Zellkerne immer kleiner. „Durch die Verkleinerung des Reaktionsvolumens verschiebt sich im Zellkern das physikalisch-chemische Gleichgewicht der Transkriptionsfaktoren hin zum DNA-gebundenen Zustand. Durch die vermehrte Bindung an die DNA bringen die Transkriptionsfaktoren schließlich den genetischen „Übersetzungsprozess“ erstmals zum Laufen,“ heißt es in einer Pressemitteilung des Instituts. Dem veränderten Volumen des Zellkerns kommt somit die Schlüsselrolle der Genomaktivierung zu.
EINSATZ VON LICHTBLATTMIKROSKOP

Erstautor der Studie, Doktorand Matthias Reisser, am Reflektions-Lichtblattmikroskop ©Elvira Eberhardt/Uni Ulm
Um die Transkriptionsfaktoren im Zellkern genau lokalisieren zu können, setzten die Wissenschaftler ein Lichtblattmikroskop, eine Weiterentwicklung des Fluoreszenzmikroskops, ein. So wurde es möglich, die einzelnen, speziell markierten Biomoleküle in den lebenden Zellen sichtbar zu machen und somit auch deren Bewegung zu verfolgen. Zur Erforschung wird nur eine dünne Schicht der Probe beleuchtet. Dies führt zu einer höheren Sensitivität. Das Verfahren soll so schonend sein, dass „die untersuchten Biomoleküle nicht unter lichtinduziertem Stress leiden und so auch keinen Schaden nehmen“, heißt es aus den Laboren. Mit dieser Untersuchungsmethode ist es möglich, „Single Molecule Tracking“-Aufnahmen in den lebenden Organismen zu erhalten und Langzeitbeobachtungen während der Embryonalentwicklung zu machen. Das Verfahren wurde übrigens am Institut für Biophysik durch Professor Gebhardt noch leistungsfähiger gemacht.
FÖRDERUNG
Eine Förderung erhielt das spannende Projekt durch die Deutsche Forschungsgemeinschaft sowie vom europäischen Wissenschaftsrat, der Studienstiftung des Deutschen Volkes und der Carl-Zeiss-Stiftung. Unterstützt wurde es zudem vom Zentrum für translationale Bildgebung (MoMAN) der Universität Ulm.
Bild oben: Hellfeldmikroskopische Aufnahme von Zebrabärblingembryonen. Das Bild entstand rund vier Stunden nach der Befruchtung ©Prof. Gilbert Weidinger/Universität Ulm
Dieser Artikel erschien in der Innovation Origins am 19.12.2018.
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