Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Nuclear architecture diagnostics within reach of the clinic

29.11.2018

A new technique that allows the study of the 3D architecture of cancer genomes might help in the design of personalized treatment strategies.

Scientists at the Max Planck Institute of Molecular Biomedicine in Münster and of the Medical Faculty of the University of Münster have developed a technique that allows the characterisation of the three-dimensional organisation of the DNA in the nucleus directly in patient’s cells.


Representation of 3D genome structure for cancer (above the diagonal) and healthy B-cells (below the diagonal). Previously known cancer-related genes are highlighted in red.

MPI Münster / Vaquerizas lab


The MPI team: Noelia Díaz, Kai Kruse and Juanma Vaquerizas

MPI Münster

The research, published in Nature Communications (online November 29, 2018), will help in diagnosing disease and, in future, guiding therapeutic intervention.

Each cell in our organism has a roughly 2-meter-long molecule of DNA – our genetic information – that needs to be properly packed inside a few micron nucleus. How the DNA is organised in the nucleus is known to play a key role for normal cellular development and function, since mutations in the mechanisms that control this process lead to developmental disorders or diseases such as cancer.

However, the exact role that the organisation of the genome plays in disease is currently unknown, since scientists have lacked the ability to thoroughly examine the 3D organisation of the genome in diseased cells.

In this new research, scientists have performed a proof-of-principle study demonstrating that the 3D genome can be directly examined in diseased cells from patients.

Subtle improvements implemented in this new technique to measure three-dimensional genome architecture, called Low-C, allowed researchers to lower the amount of biological material initially required to perform the experiments.

This enabled them to determine the spatial architecture of a diffuse large B-cell lymphoma genome.

“To be able to examine the genome architecture of the specific cells that cause disease is really exciting, since currently we do not know how the 3D genome is altered in these cells”, says Dr Noelia Díaz, a postdoctoral fellow in the Vaquerizas Laboratory who led the experimental part of the project.

The researchers then performed an advanced computational analysis of the data that revealed some surprising observations. First, the scientists were able to detect genome rearrangements – changes in the normal sequence arrangement of our genome that are a key feature of many cancers – and detected both novel and known translocations characteristic of the disease, which were then experimentally validated.

“It was reassuring to see our computational predictions validated experimentally”, says Dr Kai Kruse, a postdoctoral fellow in the Vaquerizas Laboratory who performed the computational analysis of the data.

More power to study cancer cells

But the data held more surprises. When the researchers examined a finer level of chromatin organisation into topological domains (short sections of the genome that are folded into compact knots resembling balls of yarn), they observed that new domains were present in disease cells in regions of the genome that would otherwise present no domains in healthy cells.

“This was a surprising finding, since the 3D architecture of fully developed cells is thought to be rather invariant”, says Dr Juanma Vaquerizas, a Group Leader at the Max Planck Institute for Molecular Biomedicine in Muenster, who supervised the research.

“We could observe that these new structural domains appear in regions that contain genes previously known to be associated with cancer and disease, but the functional role of these new domains is currently unknown”, says Vaquerizas.

The researchers aim now to extend their studies to more samples, to be able to determine the impact that changes in the 3D structure of the genome play in disease and to use this information in the design of personalised patient-specific treatment options.

Wissenschaftliche Ansprechpartner:

Dr. Juan M Vaquerizas
Group leader

Tel.: +49 251 70365-580
Fax: +49 251 70365-599
E-mail: jmv@mpi-muenster.mpg.de
Website: www.vaquerizaslab.org

Originalpublikation:

Noelia Díaz, Kai Kruse, Tabea Erdmann, Annette M. Staiger, German Ott, Georg Lenz, Juan M. Vaquerizas. Chromatin conformation analysis of primary patient tissue using a low input Hi-C method. Nature Communications, 29. November 2018, DOI: 10.1038/s41467-018-06961-0.

Weitere Informationen:

https://www.mpi-muenster.mpg.de/425089/20181122-lowc-vaquerizas

Dr. Jeanine Müller-Keuker | Max-Planck-Institut für molekulare Biomedizin

Further reports about: 3D DNA Max-Planck-Institut Nuclear diseased cells molekulare Biomedizin

More articles from Life Sciences:

nachricht New yeast species discovered in Braunschweig, Germany
13.12.2019 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

nachricht Saliva test shows promise for earlier and easier detection of mouth and throat cancer
13.12.2019 | Elsevier

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Virus multiplication in 3D

Vaccinia viruses serve as a vaccine against human smallpox and as the basis of new cancer therapies. Two studies now provide fascinating insights into their unusual propagation strategy at the atomic level.

For viruses to multiply, they usually need the support of the cells they infect. In many cases, only in their host’s nucleus can they find the machines,...

Im Focus: Cheers! Maxwell's electromagnetism extended to smaller scales

More than one hundred and fifty years have passed since the publication of James Clerk Maxwell's "A Dynamical Theory of the Electromagnetic Field" (1865). What would our lives be without this publication?

It is difficult to imagine, as this treatise revolutionized our fundamental understanding of electric fields, magnetic fields, and light. The twenty original...

Im Focus: Highly charged ion paves the way towards new physics

In a joint experimental and theoretical work performed at the Heidelberg Max Planck Institute for Nuclear Physics, an international team of physicists detected for the first time an orbital crossing in the highly charged ion Pr⁹⁺. Optical spectra were recorded employing an electron beam ion trap and analysed with the aid of atomic structure calculations. A proposed nHz-wide transition has been identified and its energy was determined with high precision. Theory predicts a very high sensitivity to new physics and extremely low susceptibility to external perturbations for this “clock line” making it a unique candidate for proposed precision studies.

Laser spectroscopy of neutral atoms and singly charged ions has reached astonishing precision by merit of a chain of technological advances during the past...

Im Focus: Ultrafast stimulated emission microscopy of single nanocrystals in Science

The ability to investigate the dynamics of single particle at the nano-scale and femtosecond level remained an unfathomed dream for years. It was not until the dawn of the 21st century that nanotechnology and femtoscience gradually merged together and the first ultrafast microscopy of individual quantum dots (QDs) and molecules was accomplished.

Ultrafast microscopy studies entirely rely on detecting nanoparticles or single molecules with luminescence techniques, which require efficient emitters to...

Im Focus: How to induce magnetism in graphene

Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.

Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Supporting structures of wind turbines contribute to wind farm blockage effect

13.12.2019 | Physics and Astronomy

Chinese team makes nanoscopy breakthrough

13.12.2019 | Physics and Astronomy

Tiny quantum sensors watch materials transform under pressure

13.12.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>