Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Fight Against Genome Parasites

05.06.2013
With roughly 50%, the human genome is densely populated with genome parasites, and so is the DNA of other animals, plants and fungi. Many of these selfish DNA elements are able to freely move around in the host’s genetic material. They are referred to as transposons and their mobility causes DNA breaks and mutations that can lead to severe genome damage.

Although they are harmful, most organisms do not specifically eliminate transposons from their DNA. Such a massive intervention might bear too much of a risk for germ cell genomes and hence a species reproductive fitness. To deal with the potential dangers, plants and animals possess defense systems – also seen as sort of a ‘genome immune system’.

In all cases, these are based on small RNA silencing mechanisms and hence date probably back to the early days of eukaryotic evolution. The ancient silencing systems are able to selectively interfere with transposon expression preventing them from causing damage.

In animals, the most prominent of these silencing pathways is the so-called piRNA pathway. At its core act so-called RNA induced silencing complexes (RISC) that are composed of PIWI proteins bound to 22-30nt long piRNAs. Via the small RNA, PIWI complexes recognize transposon RNAs and this induces degradation of the transposon RNA and feeds back negatively on the encoding locus on the host DNA to inhibit transposon transcription.

Pioneering spirit at IMBA
The field of piRNA research is relatively young and only a handful of experts exist worldwide. One of them is the molecular biologist Julius Brennecke. Since 7 years the IMBA group leader is investigating transposon control mechanisms in Drosophila gonads. The fruitfly is one of the genetic workhorses of molecular geneticists and many aspects of piRNA biology have been pioneered in this model system. Brennecke’s fascination for this system arose during his postdoctoral studies in the US: “This is one of the most ancient host-parasite conflicts and to understand it at the molecular and genetic level is simply fascinating”.
With his transition to IMBA in Vienna, he managed to establish this highly competitive field in Austria. His work has a pioneering spirit, since the archaic piRNA-signalling pathway and his underlying mechanisms are still poorly understood. “We really want to know in detail, how the fly manages to keep transposons in check”, says Brennecke.

With their recent work, Brennecke and his team made a major step forward in the dissection of the piRNA pathway. With a mix of genetic, molecular and computational methods the team performed a screen in the Drosophila ovary for factors involved in the piRNA pathway. All in all they examined 7,000 different genes and manually inspected around 60.000 fruitflies for defects in transposon silencing.

Fly library as goldmine of knowledge
For their screen, Brennecke and his group took advantage of the Vienna Drosophila RNAi Center (VDRC) library, a collection of ~30.000 fly stocks each allowing the silencing of a specific gene in a desired cell type. The VDRC library was established at the IMBA/IMP campus under leadership of Barry Dickson and Krystyna Keleman and is now run by the Campus Support Facility (CSF). From there, flies are sent out to institutes and research centers all over the globe. “The Vienna fly library is a worldwide unique resource that allows systematic studies of gene function in virtually every aspect of fruitfly biology”, compliments Brennecke.

In their two years of work, Brennecke and his group discovered around 50 genes that are important for a fully functional piRNA pathway. Dominik Handler, PhD student in Brennecke’s lab and first author of the study, explains: “For many of the identified genes, orthologous genes can be identified in the human genome, too. Our results will therefore have a broad impact on the general understanding of this transposon silencing system.” Some of the identified genes are required for the biogenesis of piRNAs, but others connect the defense system to basic processes such as mitochondria-metabolism, RNA transport, transcription or chromatin-biology.

Signalling-pathway with great potential
The obtained results set the stage for multiple lines of future investigations, underlines Brennecke. The identified factors will play key roles in understanding the mechanistic framework of the pathway, but they will also be unique entry points into understanding how this silencing system is embedded into the general process of oogenesis. Key question along those lines are how piRNAs are passed from generation to generation and what evolutionary benefit the host might have from transposons. Brennecke is fascinated by the close interplay between possible advantages and dangers that transposons and other repetitive sequences have for host genome regulation. He is confident: “Core concepts of the piRNA pathway are highly conserved amongst organisms. I have no doubt, that our results will have far reaching implications for the understanding of genome evolution and possibly even aspects of human medicine.”

Original publication: The Genetic Makeup of the Drosophila piRNA Pathway, Molecular Cell, Doi: 10.1016/j.molcel.2013.04.031

Julius Brennecke:
Born in Munich, Brennecke studied biology in Heidelberg, Germany. Since his time as postdoc in Cold Spring Harbor (US), he investigates the piRNA pathway in Drosophila. He was involved in the discovery of basic principles, underlying this genetic defense system. Since 2009 he is group leader at the Institute of Molecular Biotechnology (IMBA) in Vienna. The focus of Julius Brennecke and his group lies on investigating the small regulatory piRNAs and their corresponding signaling pathways.
IMBA:
The Institute of Molecular Biotechnology (IMBA) combines basic and applied research in the fields of molecular biology, stem cell biology and biomedicine. Interdisciplinary research groups address functional genetic questions, particularly those related to the origin of disease. IMBA is a subsidiary of the Austrian Academy of Sciences, the leading organization promoting non-university academic basic research in Austria. Earlier this year IMBA was voted as second to top international workplace for postdoctoral researchers, by readers of the US based and online life sciences magazine, The Scientist.
Austrian Academy of Sciences (ÖAW):
Within the Austrian Academy of Sciences, renowned researchers from more than 60 research institutions have formed a comprehensive knowledge pool covering a wide array of disciplines for the sake of progress in science as a whole. All of the Academy's activities are closely networked at national, EU, and international level with university and non-university partners.

Elena Bertolini | Newswise
Further information:
http://www.oeaw.ac.at
http://www.imba.oeaw.ac.at

More articles from Life Sciences:

nachricht Not of Divided Mind
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht CRISPR meets single-cell sequencing in new screening method
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>