Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists characterise cancer genes using ground-breaking new method

07.05.2018

In a paper in the journal “Science”, researchers from the Vienna BioCenter combine cutting-edge technologies to decipher regulatory functions of important cancer genes. Key to this success is an innovative method called “SLAMseq”, which allows the direct detection of sudden changes in gene expression and thereby revolutionizes the way scientists can investigate effects of genes and drugs.

All cells in our body carry the dictionary of genetic information, the human genome. However, their shape and function are determined by which genes are read from this dictionary and translated into proteins, the building blocks of a cell.


Scientists in Vienna characterised important cancer genes using SLAMseq, an innovative method for visualizing sudden changes in gene transcription

IMP

The “reading” of active genes starts with their transcription into so-called messenger RNAs (mRNAs), a process that is controlled through a complex network of transcriptional regulators. Mutations in these regulators can alter the function and identity of cells and thereby lead to cancer and other human diseases. At the same time, blocking abnormal transcription can kill cancer cells, which makes some transcriptional regulators attractive targets for drug development.

To understand the function of transcriptional regulators, it is critical to know which genes they directly control. However, defining these genes has remained difficult, because commonly used methods such as mRNA sequencing cannot distinguish direct targets of a regulator from indirect effects. Instead of just measuring all mRNAs in a cell, a new profiling method called “SLAMseq” enables researchers to detect mRNAs that are newly made during a defined period of time.

The inventor of this method, Stefan Ameres and his team (Institute of Molecular Biotechnology - IMBA) now partnered with the lab of Johannes Zuber (Research Institute of Molecular Pathology - IMP) to further develop SLAMseq for investigating direct targets of cancer genes and targeted drugs.

As now reported in the journal “Science”, the team used this approach to illuminate the function of two important transcriptional regulators, BRD4 and MYC, which are pursued as possible drug targets in cancer. To decipher their direct transcriptional targets, the scientists combined SLAMseq with new tools for targeted protein degradation, which allowed them to eliminate BRD4 and MYC within 30 minutes and measure resulting changes in mRNA production over the next hour.

These experiments could clarify the primary functions of BRD4 and MYC in transcription, which had been subject to a long and controversial debate in the scientific community.

The simplicity of SLAMseq also enabled the team to investigate direct effects of cancer therapeutics at an unprecedented level of depth. Inhibitors of BRD4, which are currently tested in several clinical trials, turned out to trigger either highly specific or wide-spread transcriptional effects, depending on the dose at which they are applied. Together with collaborators at the pharmaceutical company Boehringer Ingelheim, the scientists have also started to use SLAMseq for exploring combination therapies, which is one of many future applications of the method.

“We are very excited about the opportunities our method opens for the future of cancer research”, says Matthias Muhar, a PhD student in the Zuber lab who spearheaded the study. “SLAMseq equips any biological and clinical research lab with a very simple tool to identify direct transcriptional targets of any gene, pathway or drug.”. He thinks that cancer researchers world-wide will adopt the method quickly for the development and testing of new cancer therapies.

Moreover, the success of this study testifies to the scientific excellence and collaborative spirit thriving at the Vienna BioCenter. The study built on a collaboration between research groups at the three research institutes IMP, IMBA and MFPL; a partnership with Lexogen, a biotech company at the Vienna BioCenter, has already led to the development of a SLAMseq kit to distribute the method to the scientific community.


Original publication
Muhar, M., et al. (2018): “SLAMseq defines direct gene-regulatory functions of the BRD4-MYC axis.” Science. doi: 10.1126/science.aao2793

Image Caption
Scientists in Vienna characterised important cancer genes using SLAMseq, an innovative method for visualizing sudden changes in gene transcription.
The image and other media materials are provided at: https://imp.ac.at/supplements

About the Vienna BioCenter
Vienna BioCenter (VBC) is a leading life sciences hub in Europe, offering an extraordinary combination of research, business and education in a single location. About 1,700 employees, 86 research groups, 18 biotech companies, 1,300 students and scientists from 70 nations create a highly dynamic and stimulating environment. www.viennabiocenter.org

About the IMP
The Research Institute of Molecular Pathology (IMP) in Vienna pursues world-class research in basic molecular biology. It is located at the Vienna BioCenter and largely sponsored by Boehringer Ingelheim. With over 200 scientists from 40 countries, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. www.imp.ac.at

About IMBA
IMBA - Institute of Molecular Biotechnology is one of the leading biomedical research institutes in Europe focusing on cutting-edge functional genomics and stem cell technologies. IMBA is located at the Vienna BioCenter, the vibrant cluster of universities, research institutes and biotech companies in Austria. IMBA is a basic research institute of the Austrian Academy of Sciences, the leading national sponsor of non-university academic research. www.imba.oeaw.ac.at

Media Contact IMP
Benedikt Mandl
T: +43 1 79730 3627
E: benedikt.mandl@imp.ac.at

Media Contact IMBA
Ines Méhu-Blantar
T: +43 664 808 47 3628
E: ines.mehublantar@imba.oeaw.ac.at

Weitere Informationen:

https://imp.ac.at/supplements

Dr. Heidemarie Hurtl | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Antibiotics: New substances break bacterial resistance
12.11.2019 | Martin-Luther-Universität Halle-Wittenberg

nachricht How the Zika virus can spread
11.11.2019 | Goethe-Universität Frankfurt am Main

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A new quantum data classification protocol brings us nearer to a future 'quantum internet'

The algorithm represents a first step in the automated learning of quantum information networks

Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...

Im Focus: Distorted Atoms

In two experiments performed at the free-electron laser FLASH in Hamburg a cooperation led by physicists from the Heidelberg Max Planck Institute for Nuclear physics (MPIK) demonstrated strongly-driven nonlinear interaction of ultrashort extreme-ultraviolet (XUV) laser pulses with atoms and ions. The powerful excitation of an electron pair in helium was found to compete with the ultrafast decay, which temporarily may even lead to population inversion. Resonant transitions in doubly charged neon ions were shifted in energy, and observed by XUV-XUV pump-probe transient absorption spectroscopy.

An international team led by physicists from the MPIK reports on new results for efficient two-electron excitations in helium driven by strong and ultrashort...

Im Focus: A Memory Effect at Single-Atom Level

An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.

The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.

Im Focus: Shedding new light on the charging of lithium-ion batteries

Exposing cathodes to light decreases charge time by a factor of two in lithium-ion batteries.

Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory have reported a new mechanism to speed up the charging of lithium-ion...

Im Focus: Visible light and nanoparticle catalysts produce desirable bioactive molecules

Simple photochemical method takes advantage of quantum mechanics

Northwestern University chemists have used visible light and extremely tiny nanoparticles to quickly and simply make molecules that are of the same class as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

High entropy alloys for hot turbines and tireless metal-forming presses

05.11.2019 | Event News

Smart lasers open up new applications and are the “tool of choice” in digitalization

30.10.2019 | Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

 
Latest News

How the Zika virus can spread

11.11.2019 | Life Sciences

Researchers find new potential approach to type 2 diabetes treatment

11.11.2019 | Health and Medicine

Medica 2019: Arteriosclerosis - new technologies help to find proper catheters and location of vasoconstriction

11.11.2019 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>