Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

Need for Speed: High-speed Measurements of Molecular Motion in the Cell Nucleus

03.12.2012
Heidelberg scientists study interactions between proteins and DNA in living cells

Using a new measurement technique, Heidelberg researchers have succeeded in tracking interactions between proteins and DNA in the cell nucleus at a resolution of 1/1000 of a second.


Microscopy images after bleaching the fluorescence in a circular or rectangular region. The dark “shadows” represent the bleached proteins that moved as the image was being recorded.

Picture credits: Fabian Erdel and Karsten Rippe

They were able to measure the binding of highly specialised protein complexes that specifically change the spatial structure of the genetic information, thereby controlling the readout of the DNA information. The work of Dr. Karsten Rippe and his team was carried out at the BioQuant Center of Heidelberg University and the German Cancer Research Center.

Their research has demonstrated that the positioning of nucleosomes – complexes of DNA and specialised proteins – is a precisely regulated molecular process. Aberrant regulation can be linked to several types of cancer. The results of these studies were published in the journal PNAS.

In the human genome, the DNA strands are wrapped around specific packaging proteins, the histones. Located between these complexes, called nucleosomes, are histone-free DNA sequences that connect the nucleosomes, much like a pearl necklace. “Activating a gene requires freely accessible DNA. If the corresponding DNA is occluded in the nucleosome, the gene is often turned off”, explains Dr. Rippe.

“Hence, the nucleosome positions determine the readout pattern of the DNA sequence. The free DNA between two nucleosomes is more easily accessible than the DNA sequences in a nucleosome.” Molecular machines called chromatin remodelers can use energy to move nucleosomes along the DNA chain. Thus they establish the readout pattern that, along with other factors, determines the active DNA programme of the cell.

Rippe’s team of scientists are using fluorescence microscopy to investigate how the chromatin remodelers control the readout of the genetic information. With it they were able to measure that most of the approx. one million chromatin remodelers in the human cell transiently bind to nucleosomes to test whether all the approx. 30 million nucleosomes are at the right position. A new way of measurement was needed to understand how these molecular machines work. “We had to record short binding events at a resolution of 1/1000 of a second and at the same time detect the rare events with a binding time of several seconds or even minutes”, says Karsten Rippe. Doctoral student Fabian Erdel came up with an idea that led to “Pixel-wise Photobleaching Profile Evolution Analysis”, or 3PEA, which can be used to take such measurements in living cells.

In his experiments, Fabian Erdel used a laser beam to extinguish the artificial fluorescent tag attached to the chromatin remodelers. He noticed that the “bleached” proteins produced a “shadow” when they moved while the image was being recorded. The shape of this shadow depended on how much the movement of the chromatin remodelers slowed down due to binding to nucleosomes. “It was not easy calculating duration times of binding from the shadow image, but it was worth the effort. Our method has exciting new applications because we can use it to measure the binding of proteins in living cells very quickly and precisely”, remarks Fabian Erdel.

Using 3PEA measurements, the researchers demonstrated that an individual chromatin remodeler travels through the entire cell nucleus within a single second testing more than 300 nucleosomes – mostly without becoming active. Only occasionally the molecular machine would bind to a nucleosome for several seconds or even minutes, causing it to shift position on the DNA. Dr. Rippe and his team next want to decode signals that activate the chromatin remodelers at certain locations on the genome.

For more information, go to http://malone.bioquant.uni-heidelberg.de.

Original publication:
F. Erdel, K. Rippe: Quantifying transient binding of ISWI chromatin remodelers in living cells by pixel-wise photobleaching profile evolution analysis, PNAS, 20 November 2012, vol. 109, no. 47, E3221-3230 (online 5 November 2012, doi:10.1073/pnas.1209579109).

Contact:
Dr. Karsten Rippe
BioQuant, phone: +49 (0)6221 54-51376
karsten.rippe@bioquant.uni-heidelberg.de

Heidelberg University
Communications and Marketing
Press Office, phone: +49 (0)6221 54-2311
presse@rektorat.uni-heidelberg.de

Marietta Fuhrmann-Koch | idw
Further information:
http://malone.bioquant.uni-heidelberg.de
http://www.uni-heidelberg.de

More articles from Life Sciences:

nachricht New Model of T Cell Activation
27.05.2016 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Fungi – a promising source of chemical diversity
27.05.2016 | Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie - Hans-Knöll-Institut (HKI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Tiroler Technologie zur Abwasserreinigung weltweit erfolgreich

Auf biologischem Weg und mit geringem Energieeinsatz wandelt ein an der Universität Innsbruck entwickeltes Verfahren in Kläranlagen anfallende Stickstoffverbindungen in unschädlichen Luftstickstoff um. Diese innovative Technologie wurde nun gemeinsam mit dem US-Wasserdienstleister DC Water weiterentwickelt und vermarktet. Für die Kläranlage von Washington DC wird die bisher größte DEMON®-Anlage errichtet.

Das DEMON®-Verfahren wurde bereits vor elf Jahren entwickelt und von der Universität Innsbruck zum Patent angemeldet. Inzwischen wird die Technologie in rund...

Im Focus: Worldwide Success of Tyrolean Wastewater Treatment Technology

A biological and energy-efficient process, developed and patented by the University of Innsbruck, converts nitrogen compounds in wastewater treatment facilities into harmless atmospheric nitrogen gas. This innovative technology is now being refined and marketed jointly with the United States’ DC Water and Sewer Authority (DC Water). The largest DEMON®-system in a wastewater treatment plant is currently being built in Washington, DC.

The DEMON®-system was developed and patented by the University of Innsbruck 11 years ago. Today this successful technology has been implemented in about 70...

Im Focus: Optische Uhren können die Sekunde machen

Eine Neudefinition der Einheit Sekunde auf der Basis von optischen Uhren wird realistisch

Genauer sind sie jetzt schon, aber noch nicht so zuverlässig. Daher haben optische Uhren, die schon einige Jahre lang als die Uhren der Zukunft gelten, die...

Im Focus: Computational High-Throughput-Screening findet neue Hartmagnete die weniger Seltene Erden enthalten

Für Zukunftstechnologien wie Elektromobilität und erneuerbare Energien ist der Einsatz von starken Dauermagneten von großer Bedeutung. Für deren Herstellung werden Seltene Erden benötigt. Dem Fraunhofer-Institut für Werkstoffmechanik IWM in Freiburg ist es nun gelungen, mit einem selbst entwickelten Simulationsverfahren auf Basis eines High-Throughput-Screening (HTS) vielversprechende Materialansätze für neue Dauermagnete zu identifizieren. Das Team verbesserte damit die magnetischen Eigenschaften und ersetzte gleichzeitig Seltene Erden durch Elemente, die weniger teuer und zuverlässig verfügbar sind. Die Ergebnisse wurden im Online-Fachmagazin »Scientific Reports« publiziert.

Ausgangspunkt des Projekts der IWM-Forscher Wolfgang Körner, Georg Krugel und Christian Elsässer war eine Neodym-Eisen-Stickstoff-Verbindung, die auf einem...

Im Focus: University of Queensland: In weniger als 2 Stunden ans andere Ende der Welt reisen

Ein internationales Forschungsteam, darunter Wissenschaftler der University of Queensland, hat im Süden Australiens einen erfolgreichen Hyperschallgeschwindigkeitstestflug absolviert und damit futuristische Reisemöglichkeiten greifbarer gemacht.

Flugreisen von London nach Sydney in unter zwei Stunden werden, dank des HiFiRE Programms, immer realistischer. Im Rahmen dieses Projekts werden in den...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

Wie sieht die Schifffahrt der Zukunft aus? - IAME-Jahreskonferenz in Hamburg

27.05.2016 | Veranstaltungen

Technologische Potenziale der Multiparameteranalytik

27.05.2016 | Veranstaltungen

Umweltbeobachtung in nah und fern

27.05.2016 | Veranstaltungen

 
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Stressoren erkennen, Belastungen reduzieren, Fachwissen erlangen

27.05.2016 | Seminare Workshops

HDT SOMMERAKADEMIE 2016

27.05.2016 | Seminare Workshops

11 Millionen Euro für die Erforschung von Magnetfeldsensoren für die medizinische Diagnostik

27.05.2016 | Förderungen Preise