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Sunday, 21 February 2021

Scientists capture the highest resolution images of a single MOLECULE of DNA yet, showing how atoms 'dance' as they twist and writhe

  • The team took the highest resolution images of a single DNA molecule to date
  • Images combined with supercomputer simulations have made it possible to see the position of every single atom in the DNA and how it twists and writhes 
  • Study reveals as the DNA dances, it adopts exotic twisted and writhed shapes 
  • Being able to observe DNA in such detail could help to accelerate the development of new gene therapies and treat diseases and life-long conditionsThe highest resolution images of a single molecule of DNA ever captured have been taken by a team of scientists, and they show atoms 'dancing' as they twist and writhe.

    Researchers from Sheffield, Leeds and York universities combined advanced atomic microscopy with supercomputer simulations to create videos of the molecules.

    The resolution combined with the simulations allow the team to map and observe the movement and position of every single atom within a single strand of DNA. 

    Being able to observe DNA in such detail could help to accelerate the development of new gene therapies, according to the British team behind the study. Researchers from Sheffield, Leeds and York universities combined advanced atomic microscopy with supercomputer simulations to create videos of the molecules

    Researchers from Sheffield, Leeds and York universities combined advanced atomic microscopy with supercomputer simulations to create videos of the molecules

    DNA MINICIRCLES: CELLS JOINED TOGETHER TO FORM A LOOP

    Minicircles are circular DNA elements that are easier to program and manipulate by scientists.

    The molecule of DNA is joined at both ends to form a loop and they are stripped of antibiotic resistance markers or origins of replication.

    They can be used create sustained expressions in cells and tissues that could be used in future gene therapy.

    Research from Stanford suggested DNA minicircles are potential indicators of health and ageing and may act as early markers for disease.

    Close up analysis of a minicircle revealed they can be very active.

    They wrinkled, bubbled, kinked, denatured, and strangely shaped.

    Scientists say one day they will be able to control those shapes to create targeted treatments for disease.

    The footage shows in unprecedented detail how the stresses and strains that are placed on DNA when it is crammed inside cells can change its shape.

    Previously scientists were only able to see DNA by using microscopes that are limited to taking static images, video reveals movement of the atoms. 

    Images are so detailed it is possible to see the iconic double helical structure of DNA, but when combined with the simulations, the researchers were able to see the position of every single atom in the DNA and how it twists and writhes.

    Every human cell contains two metres of DNA and in order to fit inside our cells it has evolved to twist, turn, and coil itself up. 

    That means that loopy DNA is everywhere in the genome, forming twisted structures which show more dynamic behaviour than their relaxed counterparts.

    The team looked at DNA minicircles, which are special because the molecule is joined at both ends to form a loop. 

    This loop enabled the researchers to give the DNA minicircles an extra added twist, making the DNA dance more vigorously.

    When the researchers imaged relaxed DNA, without any twists, they saw that it did very little. 

    However, when they gave the DNA an added twist, it suddenly became far more dynamic and could be seen to adopt some very exotic shapes. 

    These exotic dance-moves were found to be the key to finding binding partners for the DNA, as when they adopt a wider range of shapes, then a greater variety of other molecules find it attractive.

    Images are so detailed it is possible to see the iconic double helical structure of DNA, but when combined with the simulations, the researchers were able to see the position of every single atom in the DNA and how it twists and writhes

    Images are so detailed it is possible to see the iconic double helical structure of DNA, but when combined with the simulations, the researchers were able to see the position of every single atom in the DNA and how it twists and writhesResearchers from Sheffield, Leeds and York universities combined advanced atomic microscopy with supercomputer simulations to create videos of the molecules

    Researchers from Sheffield, Leeds and York universities combined advanced atomic microscopy with supercomputer simulations to create videos of the molecules

    DNA MINICIRCLES: CELLS JOINED TOGETHER TO FORM A LOOP

    Minicircles are circular DNA elements that are easier to program and manipulate by scientists.

    The molecule of DNA is joined at both ends to form a loop and they are stripped of antibiotic resistance markers or origins of replication.

    They can be used create sustained expressions in cells and tissues that could be used in future gene therapy.

    Research from Stanford suggested DNA minicircles are potential indicators of health and ageing and may act as early markers for disease.

    Close up analysis of a minicircle revealed they can be very active.

    They wrinkled, bubbled, kinked, denatured, and strangely shaped.

    Scientists say one day they will be able to control those shapes to create targeted treatments fr disease\

    Images are so detailed it is possible to see the iconic double helical structure of DNA, but when combined with the simulations, the researchers were able to see the position of every single atom in the DNA and how it twists and writhesThese exotic dance-moves were found to be the key to finding binding partners for the DNA, as when they adopt a wider range of shapes, then a greater variety of other molecules find it attractive

    These exotic dance-moves were found to be the key to finding binding partners for the DNA, as when they adopt a wider range of shapes, then a greater variety of other molecules find it attractive

    Previous research from Stanford suggested DNA minicircles are potential indicators of health and ageing and may act as early markers for disease.

    As the DNA minicircles can twist and bend, they can also become very compact.

    Being able to study DNA in such detail could accelerate the development of new gene therapies by utilising how twisted and compacted DNA circles can squeeze their way into cells.

    Dr Alice Pyne, Lecturer in Polymers & Soft Matter at the University of Sheffield, who captured the footage, said: 'Seeing is believing, but with something as small as DNA, seeing the helical structure of the entire DNA molecule was extremely challenging.

    'The videos we have developed enable us to observe DNA twisting in a level of detail that has never been seen before.' 

    Previous research from Stanford suggested DNA minicircles are potential indicators of health and ageing and may act as early markers for disease

    Previous research from Stanford suggested DNA minicircles are potential indicators of health and ageing and may act as early markers for disease

    Being able to study DNA in such detail could accelerate the development of new gene therapies by utilising how twisted and compacted DNA circles can squeeze their way into cells

    Being able to study DNA in such detail could accelerate the development of new gene therapies by utilising how twisted and compacted DNA circles can squeeze their way into cells

    Professor Lynn Zechiedrich from Baylor College of Medicine in Houston Texas, USA, who made the DNA minicircles used in the study the work was significant.

    'They show, with remarkable detail, how wrinkled, bubbled, kinked, denatured, and strangely shaped they are which we hope to be able to control someday.'

    Dr Sarah Harris from the University of Leeds, who supervised the research, said the work shows the laws of physics apply as well to the tiny looped DNA as they do to sub-atomic particles and entire galaxies.

    'We can use supercomputers to understand the physics of twisted DNA. This should help researchers design bespoke minicircles for future therapies.'

    The study, Combining high-resolution atomic force microscopy with molecular dynamics simulations shows that DNA supercoiling induces kinks and defects that enhance flexibility and recognition, is published in Nature Communications

    DNA: A COMPLEX CHEMICAL THAT CARRIES GENETIC INFORMATION IN ALMOST ALL ORGANISMS

    DNA, or deoxyribonucleic acid, is a complex chemical in almost all organisms that carries genetic information.

    It is located in chromosomes the cell nucleus and almost every cell in a person's body has the same DNA. 

    It is composed of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T).

    The structure of the double-helix DNA comes from adenine binding with thymine and cytosine binding with guanine. 

    Human DNA consists of three billion bases and more than 99 per cent of those are the same in all people.

    The order of the bases determines what information is available for maintaining an organism (similar to the way in which letters of the alphabet form sentences).

    The DNA bases pair up with each other and also attach to a sugar molecule and phosphate molecule, combining to form a nucleotide.

    These nucleotides are arranged in two long strands that form a spiral called a double helix.

    The double helix looks like a ladder with the base pairs forming the rungs and the sugar and phosphate molecules forming vertical sidepieces.

    A new form of DNA was recently discovered inside living human cells for the first time.

    Named i-motif, the form looks like a twisted 'knot' of DNA rather than the well-known double helix. 

    It is unclear what the function of the i-motif is, but experts believe it could be for 'reading' DNA sequences and converting them into useful substances.

    Source: US National Library of MedicineImages are so detailed it is possible to see the iconic double helical structure of DNA, but when combined with the simulations, the researchers were able to see the position of every single atom in the DNA and how it twists and writhes

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