Chromosome imaging promises breakthrough treatments

EU-funded researchers are developing pioneering tools and techniques that will enable scientists to view chromosomes in unprecedented detail, greatly advancing research into life-saving treatments for cancer and cures for many genetic disorders.

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Countries
Countries
  Algeria
  Argentina
  Australia
  Austria
  Bangladesh
  Belarus
  Belgium
  Benin
  Bolivia
  Bosnia and Herzegovina
  Brazil
  Bulgaria
  Burkina Faso
  Cambodia
  Cameroon
  Canada
  Cape Verde
  Chile
  China
  Colombia
  Costa Rica
  Croatia
  Cyprus
  Czechia
  Denmark
  Ecuador
  Egypt
  Estonia
  Ethiopia
  Faroe Islands
  Finland
  France
  French Polynesia
  Georgia


  Infocentre

Published: 26 February 2019  
Related theme(s) and subtheme(s)
Health & life sciencesMajor diseases  |  Medical research  |  Molecular biology  |  Public health
Innovation
Research policyHorizon 2020
SMEs
Countries involved in the project described in the article
Denmark  |  Netherlands  |  United Kingdom
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Chromosome imaging promises breakthrough treatments

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© crystaleyestudio #67642722, 2019 source: stock.adobe.com

Chromosomes, each containing hundreds or thousands of genes, act like a detailed instruction manual for how cells should develop and behave. The human genome is made up of 23 chromosome pairs containing more than 3 billion base pairs of DNA, but even the smallest mutation or variation in the structure of a chromosome can have an enormous impact on human development and disease.

To fully understand the range of diseases linked to errors in cell division, scientists must be able to examine in detail both healthy and diseased chromosomes. Better imaging and understanding of chromosomal mechanisms will increase knowledge of the causes of human diseases and aid drug discovery. The EU-funded CHROMAVISION project is addressing this challenge.

The project’s researchers have developed a breakthrough imaging and manipulation platform that enables molecular biologists to zoom in on minuscule details of chromosomes in all their complexity. It will allow scientists to automatically isolate individual chromosomes from small tissue or cell samples and have them delivered to a super-resolution microscope.

‘Chromosomal abnormalities are characteristic of many disorders such as cancer, impaired fertility due to maternal ageing, and neurological disorders such as fragile X syndrome,’ says CHROMAVISION project coordinator Gijs Wuite at Vrije Universiteit Amsterdam. ‘We are therefore aiming to greatly improve images of chromosomes in order to understand these abnormalities and the many important diseases that arise from faulty chromosome segregation.’

Single-molecule manipulation

Chromosomal abnormalities are usually most clearly revealed during the metaphase stage of the cell life cycle, when chromosomes are thickened and condensed just before cell division. The CHROMAVISION researchers therefore focused on developing novel solutions to automatically isolate individual metaphase chromosomes from tissue and cell samples.

The approach makes use of a number of cutting-edge single-molecule manipulation techniques. These include an innovative opto-fluidic chip – a lab-on-a-chip device capable of isolating chromosomes from other cellular material – and optical tweezers to capture and manipulate the individual chromosomes. Isolated chromosomes can then be imaged in 3D via super-resolution fluorescent microscopy.

Combined, these tools form the Super-Resolution Correlative Tweezers Fluorescence Microscope, a device for chromosomal imaging commercialised by industrial project partner Lumicks, a spin-off from Vrije Universiteit Amsterdam which supplies dynamic single-molecule analysis instruments to researchers.

High-resolution 3D images will enable researchers to study chromosomes in extraordinary detail, addressing key challenges in clinical and fundamental research and potentially resulting in breakthrough discoveries through the identification of abnormalities that could be associated with disease.

3D, super-resolution, real-time images

‘This instrument will, for the first time, enable 3D, super-resolution, real-time metaphase chromosome observation and manipulation studies under near-physiological conditions,’ says Wuite. ‘The tools and workflow for imaging metaphase chromosomes are now more or less finished and we are actively working on demonstration projects to illustrate the power of the combination of techniques.’

The platform will also have significant clinical value, allowing the identification and monitoring of cancer heterogeneity, the genomic instability and diversity of tumours that can make them resistant to treatment.

‘Better imaging and understanding of the chromosomal mechanisms will greatly expand our knowledge of the causes and origins of human diseases and will assist in drug discovery and the development of new treatments,’ Wuite says.

Project details

  • Project acronym: CHROMAVISION
  • Participants: the Netherlands (Coordinator), Denmark, United Kingdom
  • Project N°: 665233
  • Total costs: € 3 567 025
  • EU contribution: € 3 567 025
  • Duration: June 2015 to May 2019

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