Posts tagged cell cultures
Articles and news from the latest research reports.
First signals from brain nerve cells with ultrathin nanowires
Electrodes operated into the brain are today used in research and to treat diseases such as Parkinson’s. However, their use has been limited by their size. At Lund University in Sweden, researchers have, for the first time, succeeded in implanting an ultrathin nanowire-based electrode and capturing signals from the nerve cells in the brain of a laboratory animal.
The researchers work at Lund University’s Neuronano Research Centre in an interdisciplinary collaboration between experts in subjects including neurophysiology, biomaterials, electrical measurements and nanotechnology. Their electrode is composed of a group of nanowires, each of which measures only 200 nanometres (billionths of a metre) in diameter.
Such thin electrodes have previously only been used in experiments with cell cultures.
“Carrying out experiments on a living animal is much more difficult. We are pleased that we have succeeded in developing a functioning nano-electrode, getting it into place and capturing signals from nerve cells”, says Professor Jens Schouenborg, who is head of the Neuronano Research Centre.
He sees this as a real breakthrough, but also as only a step on the way. The research group has already worked for several years to develop electrodes that are thin and flexible enough not to disturb the brain tissue, and with material that does not irritate the cells nearby. They now have the first evidence that it is possible to obtain useful nerve signals from nanometre-sized electrodes.
The research will now take a number of directions. The researchers want to try and reduce the size of the base to which the nanowires are attached, improve the connection between the electrode and the electronics that receive the signals from the nerve cells, and experiment with the surface structure of the electrodes to see what produces the best signals without damaging the brain cells.
“In the future, we hope to be able to make electrodes with nanostructured surfaces that are adapted to the various parts of the nerve cells – parts that are no bigger than a few billionths of a metre. Then we could tailor-make each electrode based on where it is going to be placed and what signals it is to capture or emit”, says Jens Schouenborg.
When an electrode is inserted into the brain of a patient or a laboratory animal, it is generally anchored to the skull. This means that it doesn’t move smoothly with the brain, which floats inside the skull, but rather rubs against the surrounding tissue, which in the long term causes the signals to deteriorate. The Lund group’s electrodes will instead be anchored by their surface structure.
“With the right pattern on the surface, they will stay in place yet still move with the body – and the brain – thereby opening up for long-term monitoring of neurones”, explains Jens Schouenborg.
He praises the collaboration between medics, physicists and others at the Neuronano Research Centre, and mentions physicist Dmitry B. Suyatin in particular. He is the principal author of the article which the researchers have now published in the international journal PLOS ONE.
The overall goal of the Neuronano Research Centre is to develop electrodes that can be inserted into the brain to study learning, pain and other mechanisms, and, in the long term, to treat conditions such as chronic pain, depression and Parkinson’s disease.
(Source: lunduniversity.lu.se)
Research update: Imaging fish in 3-D
Zebrafish larvae — tiny, transparent and fast-growing vertebrates — are widely used to study development and disease. However, visually examining the larvae for variations caused by drugs or genetic mutations is an imprecise, painstaking and time-consuming process.
Engineers at MIT have now built an automated system that can rapidly produce 3-D, micron-resolution images of thousands of zebrafish larvae and precisely analyze their physical traits. The system, described in the Feb. 12 edition of Nature Communications, offers a comprehensive view of how potential drugs affect vertebrates, says Mehmet Fatih Yanik, senior author of the paper.
“Complex processes involving organs cannot be accurately recapitulated in cell culture today. Existing 3-D tissue models are still far too simple to model live animals,” says Yanik, an MIT associate professor of electrical engineering and computer science and biological engineering. “In whole animals, the biology is far more complicated.”
Lead authors of the paper are MIT graduate student Carlos Pardo-Martin and Amin Allalou, a visiting student at MIT. Other authors are MIT senior research scientist Peter Eimon, MIT intern Jaime Medina, and Carolina Wahlby of the Broad Institute.
Zebrafish are genetically similar to humans and have many of the same developmental pathways, so scientists often use them to model human diseases including cancer, diabetes, Parkinson’s disease and autism.
Using the new technology, researchers can grow larvae in tiny wells and flow them through a channel to an imaging platform. Once there, the embryos are rotated and 320 images are taken from different angles, allowing 3-D reconstructions to be made using optical projection tomography (OPT). Getting larvae to the platform takes about 15 seconds, and the imaging takes only 2.5 seconds. This allows hundreds or thousands of larvae to be imaged within hours.
In a 2010 paper, Yanik’s team described the system that transports the embryos to the imaging platform, which they combined with high-resolution two-dimensional imaging. In the latest version, they developed a high-speed OPT imaging technique, which takes hundreds of two-dimensional images and subsequently generates a 3-D image, similar to a CT scan.
They also created a computer algorithm that can measure hundreds of traits and use that information to create a comprehensive phenotype map — the overall description of an organism’s characteristics — for each larva. This enables rapid and detailed studies of how different drugs affect those phenotypes.
“You could probably look at almost any organ or tissue that you’re interested in,” Eimon says. “It gives researchers a way to rapidly measure and quantify and put numbers on the kinds of phenotypes and gene-expression patterns that they’ve been looking at for years and years.”
In this study, the researchers focused on the craniofacial skeleton, which is analogous to the human skull. They measured the length and volume of each of the bones that make up this structure, as well as the angles between the bones.
Each embryo was imaged five days after being treated with one of nine different teratogens — drugs that cause developmental abnormalities. The researchers compared their results with the drugs’ known effects and found that they were very consistent. They also obtained high-resolution, 3-D images of the craniofacial skeletons, which are less than a millimeter long.
“Now that we’re able to load the animals, and we can image them really quickly, and we have a way to start looking at the information, the sky’s the limit,” Pardo-Martin says. “What we have to do now is ask the big questions, because the technology has advanced.”
This kind of analysis could be very valuable for drug developers who need to efficiently screen thousands of drug candidates. It could also be used to study hard-to-detect changes in phenotype caused by genetic mutations, says Joseph Fetcho, a professor of neurobiology and behavior at Cornell University.
“A really high-throughput way to assess phenotype is very important for measuring small effects on the development of an organism,” says Fetcho, who was not part of the research team. “You can see what the phenotype looks like in a large population and quantify it in a very rigorous way.”
Four-stranded ‘quadruple helix’ DNA structure proven to exist in human cells
In 1953, Cambridge researchers Watson and Crick published a paper describing the interweaving ‘double helix’ DNA structure – the chemical code for all life.
Now, in the year of that scientific landmark’s 60th Anniversary, Cambridge researchers have published a paper proving that four-stranded ‘quadruple helix’ DNA structures – known as G-quadruplexes – also exist within the human genome. They form in regions of DNA that are rich in the building block guanine, usually abbreviated to ‘G’.
The findings mark the culmination of over 10 years investigation by scientists to show these complex structures in vivo – in living human cells – working from the hypothetical, through computational modelling to synthetic lab experiments and finally the identification in human cancer cells using fluorescent biomarkers.
The research, published in Nature Chemistry and funded by Cancer Research UK, goes on to show clear links between concentrations of four-stranded quadruplexes and the process of DNA replication, which is pivotal to cell division and production.