Regular aspirin should not be recommended for preventing heart attack and stroke in people without cardiovascular disease. The researchers, from Imperial’s National Heart and Lung Institute and King's College London, analysed 13 clinical trials – involving more than 164,000 participants – t ... more
Formation of quadruple helix DNA tracked in live human cells for the first time
The biology of DNA must be rethink
The formation of four-stranded DNA has been tracked in living human cells, allowing scientists to see how it works, and its possible role in cancer.
DNA usually forms the classic double helix shape discovered in 1953 - two strands wound around each other. Several other structures have been formed in test tubes, but this does not necessarily mean they form within living cells.
Quadruple helix structures, called DNA G-quadruplexes (G4s), have previously been detected in cells. However, the technique used required either killing the cells or using high concentrations of chemical probes to visualise G4 formation, so their actual presence within living cells under normal conditions has not been tracked, until now.
A research team from the University of Cambridge, Imperial College London and Leeds University have invented a fluorescent marker that is able to attach to G4s in living human cells, allowing them to see for the first time how the structure forms and what role it plays in cells.
Rethinking the biology of DNA
One of the lead researchers Dr Marco Di Antonio, who began the work at the University of Cambridge in the laboratory of Professor Sir Shankar Balasubramanian and now leads a research team in the Department of Chemistry at Imperial, said: "For the first time, we have been able to prove the quadruple helix DNA exists in our cells as a stable structure created by normal cellular processes. This forces us to rethink the biology of DNA. It is a new area of fundamental biology, and could open up new avenues in diagnosis and therapy of diseases like cancer.
"Now we can track G4s in real time in cells we can ask directly what their biological role is. We know it appears to be more prevalent in cancer cells and now we can probe what role it is playing and potentially how to block it, potentially devising new therapies."
The team thinks G4s form in DNA in order to temporarily hold it open and facilitate processes like transcription, where the DNA instructions are read and proteins are made. This is a form of 'gene expression', where part of the genetic code in the DNA is activated.
G4s appear to be associated more often with genes involved in cancer, and are detected in larger numbers within cancer cells. With the ability to now image a single G4 at a time, the team say they could track their role within specific genes and how these express in cancer. This fundamental knowledge could reveal new targets for drugs that interrupt the process.
The team's breakthrough in being able to image single G4s came with a rethink of mechanisms usually used to probe the working of cells. Previously, the team had used antibodies and molecules that could find and attach to the G4s, but these needed very high concentrations of the 'probe' molecule. This meant the probe molecules might be disrupting the DNA and actually causing them to form G4s, instead of detecting them naturally forming.
Dr Aleks Ponjavic, now an academic in the Schools of Physics & Astronomy and Food Science and Nutrition at the University of Leeds, jointly lead the research in the laboratory of Professor Sir David Klenerman and developed the method of visualising the new fluorescent marker with microscopy.
He said: "Scientists need special probes to see molecules within living cells, however these probes can sometimes interact with the object we are trying to see. By using single-molecule microscopy, we can observe probes at 1000-fold lower concentrations than previously used. In this case our probe binds to the G4 for just milliseconds without affecting its stability, which allows us to study G4 behaviour in their natural environment without external influence."
For the new probe, the team used a very 'bright' fluorescent molecule in small amounts that was designed to stick to the G4s very easily. The small amounts meant they couldn't hope to image every G4 in a cell, but could instead identify and track single G4s, allowing them to understand their fundamental biological role without perturbing their overall prevalence and stability in the cell.
The team were able to show that G4s appear to form and dissipate very quickly, suggesting they only form to perform a certain function, and that potentially if they lasted too long they could be toxic to normal cell processes.
- fluorescence markers
- real-time analyses
- DNA G-quadruplexes
- single molecule microscopy
Scientists have discovered that a marker in the blood could help predict the risk that a person will develop kidney cancer. The study, supported by Cancer Research UK, examined the blood of 190 people who went on to develop kidney cancer, compared to 190 controls who did not. The team found ... more
Some bacteria can release toxins that provoke their neighbours into attacking each other, a tactic that could be exploited to fight infections. Bacteria often engage in 'warfare' by releasing toxins or other molecules that damage or kill competing strains. This war for resources occurs in m ... more
Researchers have developed a three-dimensional 'organ on a chip' which enables real-time continuous monitoring of cells, and could be used to develop new treatments for disease while reducing the number of animals used in research. The device, which incorporates cells inside a 3D transistor ... more
An international team of researchers have developed a low-cost sensor made from semiconducting plastic that can be used to diagnose or monitor a wide range of health conditions, such as surgical complications or neurodegenerative diseases. The sensor can measure the amount of critical metab ... more
Parkinson’s disease is a degenerative nervous system disorder that affects more than six million people worldwide and causes nearly 120,000 deaths per year. In new research, scientists have characterised the key agents involved in spreading Parkinson’s disease in the brain, and established ... more
Scientists and engineers working at the frontier of nanotechnology face huge challenges. When the position of a single atom in a material may change the fundamental properties of that material, scientists need something in their toolbox to measure how that atom will behave. A research team ... more
Unique nanostructures which respond to stimuli, such as pH, heat and light will pave the way for safer, greener and more efficient chemical reactors. Being developed by a consortium of UK universities, the nanostructures can regulate reactions, momentum, and heat and mass transfer inside ch ... more
Peter Kündig and colleagues from Geneva University, Switzerland and Stephen Marsden and co-workers at the University of Leeds, in the UK, have developed an asymmetric Pd/N-heterocyclic carbene (NHC) - catalysed intramolecular -arylation of amide enolates, containing heteroatom sustituents. ... more
- 1Detect neurodegenerative diseases such as Alzheimer's by a simple eye scan?
- 2Fluorescence microscopy at highest spatial and temporal resolution
- 3The Mechanics of the Immune System
- 4Resolve Biosciences Launches New Era in Single-Cell Spatial Analysis
- 5Quick look under the skin
- 6New ion trap to create the world's most accurate mass spectrometer
- 7How does your computer smell?
- 8Clocking electron movements inside an atom
- 9Sartorius closes 2020 with strong growth
- 10A clear path to better insights into biomolecules
- The indestructible light beam
- Researchers develop blood test for depression, bipolar disorder
- Aviation safety: Rapid test for harmful microbes in kerosene developed
- Doping by athletes could become tougher to hide with new detection method
- First images of cells exposed to COVID-19 vaccine reveal native-like Coronav ...
- First images of cells exposed to COVID-19 vaccine reveal native-like Coronavirus spikes
- Simple, non-invasive skin swab samples are enough to quickly detect COVID-19
- Formation of quadruple helix DNA tracked in live human cells for the first time
- Pretty as a peacock: The gemstone for the next generation of smart sensors
- Print your own laboratory-grade microscope for US$18