Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Using Light To Control Protein Transport From Cell Nucleus

16.02.2016

Heidelberg researchers use light-sensitive, genetically modified protein

Light can be used to control the transport of proteins from the cell nucleus with the aid of a light-sensitive, genetically modified plant protein. Biologists from Heidelberg University and the German Cancer Research Center (DKFZ) working in the field of optogenetics have now developed such a tool.


Source: Dominik Niopek

Microscopy images of human embryonic kidney cells in culture. The cells were genetically modified to produce a glowing protein, which was linked to the new optogenetic tool (the LOV2-NES hybrid). Cells irradiated with a blue laser beam (blue arrows) show an efficient nuclear export of the protein. Non-irradiated cells (red arrows) show a constitutively nuclear localisation of the protein.

The researchers, under the direction of Dr. Barbara Di Ventura and Prof. Dr. Roland Eils, employed methods from synthetic biology and combined a light sensor from the oat plant with a transport signal. This makes it possible to use external light to precisely control the location and hence the activity of proteins in mammalian cells. The results of this research were published in the journal “Nature Communications”.

Eukaryotic cells are characterised by the spatial separation between the cell nucleus and the rest of the cell. “This subdivision protects the mechanisms involved in copying and reading genetic information from disruptions caused by other cellular processes such as protein synthesis or energy production,” explains Prof. Eils, Director of Heidelberg University's BioQuant Centre and head of the Bioinformatics Department at Ruperto Carola and the DKFZ. Proteins and other macromolecules pass through the nuclear pore complex into and out of the cell nucleus in order to control a number of biological processes.

While smaller proteins passively diffuse through the nuclear pores, larger particles must latch onto so-called carrier proteins to make the trip. Usually short peptides on the protein surface signal the carriers that the protein is ready for transport.

This signal is known as the nuclear localization signal (NLS) for transport into the nucleus, and the nuclear export sequence (NES) for transport out of the nucleus. “Artificially inducing the import or export of selected proteins would allow us to control their activities in the living cell,” says Dr. Di Ventura, group leader in Prof. Eils' department.

The Di Ventura lab has specialised in optogenetics, a relatively new field of research in synthetic biology. Optogenetics combines the methods of optics and genetics with the goal of using light to turn certain functions in living cells on and off. To this end, light-sensitive proteins are genetically modified and then introduced into specific target cells, making it possible to control their behaviour using light.

The recently published work reporting an optogenetic export system builds upon previous studies by other working groups investigating the LOV2 domain, which originally comes from the oat plant. In nature, this domain acts as a light sensor and, among other things, assists the plant in orienting to sunlight. The LOV2 domain fundamentally changes its three-dimensional structure as soon as it comes into contact with blue light, explains Dominik Niopek, primary author of the study.

The property of light-induced structure change can now be used specifically to synthetically control cellular signal sequences – like the nuclear export signal (NES). Dominik Niopek first developed a hybrid LOV2-NES protein made up of the LOV2 domain of the oat and a synthetic nuclear export signal. In the dark state, the signal is hidden in the LOV2 domain and not visible to the cell. Light causes the structure of the LOV2 to change, which renders the NES visible and triggers the export of the LOV2 domain from the nucleus.

“In principle, the hybrid LOV2-NES protein can be attached to any cellular protein and used to control its export from the nucleus using light,” says Prof. Eils. The researcher and his team demonstrated this using the p53 protein, a member of the family of cancer-suppressing proteins that monitor cell growth and prevent genetic defects during cell division. According to Roland Eils, p53 is switched off in a number of aggressive tumours by harmful genetic mutations that allow the tumour cells to reproduce uncontrollably.

Using the LOV2-NES protein, the Heidelberg researchers were able to control the export of p53 from the nucleus using light to control its gene regulatory functions. “This new ability to directly control p53 in living mammalian cells has far-reaching potential to explain its complex function in depth. We hope to uncover new clues about the role of possible defects in p53 regulation related to the development of cancer,“ says Dr. Di Ventura.

The researchers are convinced that their new optogenetic tool can also be used to make important discoveries on the dynamics of protein transport and its influence on cell behaviour. “Our research is only as good as our tools,“ says Prof. Eils. “The development of innovative molecular tools is therefore the key to understanding basic cellular functions as well as the mechanisms that cause illness.“

Original publication:
D. Niopek, P. Wehler, J. Roensch, R. Eils and B. Di Ventura: Optogenetic control of nuclear protein export. Nature Communications (published online 8 February 2016). doi: 10.1038/NCOMMS10624

Contact:
Prof. Dr. Roland Eils
Heidelberg University – Institute of Pharmacy and Molecular Biology
German Cancer Research Center
Phone +49 6221 54-51290 (University) and 42-3600 (DKFZ)
r.eils@dkfz-Heidelberg.de

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

Weitere Informationen:

http://Roland Eils' department – http://ibios.dkfz.de/tbi

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

Further reports about: Nucleus cell nucleus light sensor mammalian cells p53 proteins synthetic synthetic biology

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>