13 June 2013 Cancer Maps These charts show the mutated DNA of two children with acute lymphoblastic leukaemia. The coloured bands illustrate where large areas of the children’s DNA, called chromosomes (1–22, X and Y), once broke apart and stuck back together in an unnatural arrangement (chromosome 5 joined to chromosome 18, for example), triggering their disease. There are vital clues here as to when this event happened: the children are twins, and their identically jumbled DNA suggests that the cancer originated before birth, in the womb. Other DNA mutations (shown with purple, blue or red dashes around the circumference of the rings) are unique to each twin, showing how their conditions diverged and developed separately after they were born. Unravelling the early time-lines of childhood cancers is vital for pre-natal diagnosis and post-natal treatment, especially as the disease can develop to be just as individual as we are. Written by John Ankers — Mel Greaves Richard Houlston Institute of Cancer Research, UK Published in PNAS 110(18): 7429-7433
Pop-upView Separately
13 June 2013

Cancer Maps

These charts show the mutated DNA of two children with acute lymphoblastic leukaemia. The coloured bands illustrate where large areas of the children’s DNA, called chromosomes (1–22, X and Y), once broke apart and stuck back together in an unnatural arrangement (chromosome 5 joined to chromosome 18, for example), triggering their disease. There are vital clues here as to when this event happened: the children are twins, and their identically jumbled DNA suggests that the cancer originated before birth, in the womb. Other DNA mutations (shown with purple, blue or red dashes around the circumference of the rings) are unique to each twin, showing how their conditions diverged and developed separately after they were born. Unravelling the early time-lines of childhood cancers is vital for pre-natal diagnosis and post-natal treatment, especially as the disease can develop to be just as individual as we are.

Written by John Ankers

—

Source: bpod.mrc.ac.uk

23 April 2013 Enhancing Expression Multicellular organisms contain a cornucopia of different cell types. Each has specific characteristics and functions, even though almost all contain the same genetic information. Such diversity is possible because each cell type expresses a unique subset of the genes encoded in DNA, a process controlled by non-coding sections of the genome called enhancers. Researchers don’t know much about them yet, but have recently come up with a way to identify the DNA sequences that function as enhancers and measure their activity in specific cells. Pictured are fruit fly ovary cells used to validate the method, with DNA stained fluorescent blue, and green representing the strength of enhancer activity. Scientists hope to use the technique to map the regulatory parts of the human genome and study how they’re involved in turning genes on and off during normal development and disease. Written by Daniel Cossins — Arnold Cosmas Research Institute of Molecular Pathology, Austria Reprinted with permission from AAAS. Published in Science 339(6123): 1074-1077
Pop-upView Separately
23 April 2013

Enhancing Expression

Multicellular organisms contain a cornucopia of different cell types. Each has specific characteristics and functions, even though almost all contain the same genetic information. Such diversity is possible because each cell type expresses a unique subset of the genes encoded in DNA, a process controlled by non-coding sections of the genome called enhancers. Researchers don’t know much about them yet, but have recently come up with a way to identify the DNA sequences that function as enhancers and measure their activity in specific cells. Pictured are fruit fly ovary cells used to validate the method, with DNA stained fluorescent blue, and green representing the strength of enhancer activity. Scientists hope to use the technique to map the regulatory parts of the human genome and study how they’re involved in turning genes on and off during normal development and disease.

Written by Daniel Cossins

—

Cut and Paste Parasites are closer than we might wish. Harboured by mammals, cats in particular, Toxoplasma gondii could be encountered when cleaning the cat’s litter tray or by eating raw meat. These stowaways are only dangerous to those with weak immunity and unborn babies, but studying them can help reveal the secrets of their more threatening malaria-causing cousins. Toxoplasma cannot survive alone, invading and living inside cells of unsuspecting hosts. Their break-and-enter techniques include molecular grappling hooks, cell-piercing proteins and miniature propelling motors. Researchers created Toxoplasma containing DNA-crafting ‘scissors and glue’, known as recombinases, which cut out and replace certain genes. Successfully removing a motor in this way proved that Toxoplasma could invade without it. The group of motor-lacking Toxoplasma pictured are a normal shape; the remaining pink-stained invasion equipment is seen at their tips. Written by Claire Worrall — Markus Meissner University of Glasgow, UK Reprinted by permission from Macmillan Publishers Ltd: Nature Methods Copyright 2013 Published in Nature Methods 10: 125–127
Pop-upView Separately

Cut and Paste

Parasites are closer than we might wish. Harboured by mammals, cats in particular, Toxoplasma gondii could be encountered when cleaning the cat’s litter tray or by eating raw meat. These stowaways are only dangerous to those with weak immunity and unborn babies, but studying them can help reveal the secrets of their more threatening malaria-causing cousins. Toxoplasma cannot survive alone, invading and living inside cells of unsuspecting hosts. Their break-and-enter techniques include molecular grappling hooks, cell-piercing proteins and miniature propelling motors. Researchers created Toxoplasma containing DNA-crafting ‘scissors and glue’, known as recombinases, which cut out and replace certain genes. Successfully removing a motor in this way proved that Toxoplasma could invade without it. The group of motor-lacking Toxoplasma pictured are a normal shape; the remaining pink-stained invasion equipment is seen at their tips.

Written by Claire Worrall

—

Source: bpod.mrc.ac.uk

Sticking Together Ever been defeated by a particularly tricky bit of flat-pack furniture? Even our cells struggle with DIY sometimes. Within a dividing cell, matching pairs of chromosomes must join up to exchange sections of DNA. This is a delicate process, and if the chromosomes fail to join or separate properly, new cells can end up with serious genetic abnormalities. Some complications are caused by structural faults in a molecular ‘velcro’ called cohesin, which holds the two chromosomes together. The chromosome pairs pictured come from dividing egg cells from mice lacking part of cohesin. In each case complete pairing has been disrupted: by a ‘fork’ (top left) ‘bubbles’ (top right and bottom left) or by failure to join altogether (bottom right). Knowing the crucial role of cohesin is a step towards understanding why some pregnancies fail in the early stages, as egg cells with chromosomal defects rarely survive for long after fertilisation. Written by Emma Stoye — Patricia Hunt Washington State University, USA Originally published under a Creative Commons Attribution license Published in PLoS Genetics 9(2): e1003241
Pop-upView Separately

Sticking Together

Ever been defeated by a particularly tricky bit of flat-pack furniture? Even our cells struggle with DIY sometimes. Within a dividing cell, matching pairs of chromosomes must join up to exchange sections of DNA. This is a delicate process, and if the chromosomes fail to join or separate properly, new cells can end up with serious genetic abnormalities. Some complications are caused by structural faults in a molecular ‘velcro’ called cohesin, which holds the two chromosomes together. The chromosome pairs pictured come from dividing egg cells from mice lacking part of cohesin. In each case complete pairing has been disrupted: by a ‘fork’ (top left) ‘bubbles’ (top right and bottom left) or by failure to join altogether (bottom right). Knowing the crucial role of cohesin is a step towards understanding why some pregnancies fail in the early stages, as egg cells with chromosomal defects rarely survive for long after fertilisation.

Written by Emma Stoye

—

Source: bpod.mrc.ac.uk

Spheres of Influence Although the idea of curing diseases by replacing faulty genes with healthy ones is decades old, the revolutionary potential of genetic therapy has yet to be unlocked. Any practical therapy would have to overcome the multiple challenges of inserting healthy genes into the correct tissue and targeting only malfunctioning cells, while ensuring that no harmful immune response follows. Present-day treatments tested in trials consist of injecting patients with a harmless virus loaded with the replacement gene, which the virus then splices into the host cells’ DNA. But with our immune systems honed to kill viruses, the procedure can be risky. Researchers working on alternatives have produced protein-based pellets (pictured) loaded with genetic material for delivery inside diseased cells. The nanoscale-sized pellets should be friendlier to the immune system than viruses, and could potentially also be shaped into rods, spheres or coils, to help them enter only targeted tissue. Written by Tristan Farrow — Angela Pannier University of Nebraska-Lincoln, USA Originally published under Creative Commons (CC-BY 2.0) Published in Journal of Nanobiotechnology 10:44
Pop-upView Separately

Spheres of Influence

Although the idea of curing diseases by replacing faulty genes with healthy ones is decades old, the revolutionary potential of genetic therapy has yet to be unlocked. Any practical therapy would have to overcome the multiple challenges of inserting healthy genes into the correct tissue and targeting only malfunctioning cells, while ensuring that no harmful immune response follows. Present-day treatments tested in trials consist of injecting patients with a harmless virus loaded with the replacement gene, which the virus then splices into the host cells’ DNA. But with our immune systems honed to kill viruses, the procedure can be risky. Researchers working on alternatives have produced protein-based pellets (pictured) loaded with genetic material for delivery inside diseased cells. The nanoscale-sized pellets should be friendlier to the immune system than viruses, and could potentially also be shaped into rods, spheres or coils, to help them enter only targeted tissue.

Written by Tristan Farrow

—

Source: bpod.mrc.ac.uk

Micro Menaces If DNA is the book of life, messenger RNAs are the photocopies: duplicate segments of code that move between the cell’s interior compartments to the protein-making machinery. In contrast, microRNAs have the opposite role – they attach to larger RNAs and impede their movement, preventing protein production. In cancer, certain ‘bad’ microRNAs are exported from cells to surrounding tissue where they facilitate growth by attracting blood vessels, blocking growth-inhibition messages, and hindering immune surveillance. They also promote secondary tumours by predisposing distant organs to accept break-away cancer cells. Here, researchers studying breast cancer show that tumour-promoting microRNAs are exported in an unusual way: they are not associated with the typical RNA export proteins (dyed red), instead they are in particles containing proteins (in green) which are normally linked to DNA (dyed blue). These abnormal particles are present in blood so may be useful as a diagnostic marker for breast cancer. Written by Julie Webb — Dominik Duelli Rosalind Franklin University of Medicine and Science. USA Originally published under a Creative Commons license (CC-BY-NC 3.0) Published in Nucleic Acids Research
Pop-upView Separately

Micro Menaces

If DNA is the book of life, messenger RNAs are the photocopies: duplicate segments of code that move between the cell’s interior compartments to the protein-making machinery. In contrast, microRNAs have the opposite role – they attach to larger RNAs and impede their movement, preventing protein production. In cancer, certain ‘bad’ microRNAs are exported from cells to surrounding tissue where they facilitate growth by attracting blood vessels, blocking growth-inhibition messages, and hindering immune surveillance. They also promote secondary tumours by predisposing distant organs to accept break-away cancer cells. Here, researchers studying breast cancer show that tumour-promoting microRNAs are exported in an unusual way: they are not associated with the typical RNA export proteins (dyed red), instead they are in particles containing proteins (in green) which are normally linked to DNA (dyed blue). These abnormal particles are present in blood so may be useful as a diagnostic marker for breast cancer.

Written by Julie Webb

—

Source: bpod.mrc.ac.uk

Power Up DNA might sound like a surprising choice for a building material. Yet by folding it up in different ways, DNA origami has produced tiny nanostructures designed to deliver drugs inside our bodies or to act as scaffolding beside a repairing tissue. Pictured here, a new DNA device is being developed to bore tiny tunnels into living cells. The diagram on the left shows lengths of DNA (in red) forming a hollow tube that can pierce through a cell’s membrane, producing a man-made gateway or pore. Other fragments of DNA are assembled into a honeycomb-shaped cap, forming a ‘seal’ which locks the pore to the surface of the cell. This man-made channel (shown from three different perspectives in the microscope pictures on the right) might one day be used to conduct electrical impulses into our cells, possibly supplying power to other man-made devices working hard on the inside. Written by John Ankers — Friedrich Simmel Technische Universität München, Germany Reprinted with permission from AAAS. Published in Science 338(6109): 932-936
Pop-upView Separately

Power Up

DNA might sound like a surprising choice for a building material. Yet by folding it up in different ways, DNA origami has produced tiny nanostructures designed to deliver drugs inside our bodies or to act as scaffolding beside a repairing tissue. Pictured here, a new DNA device is being developed to bore tiny tunnels into living cells. The diagram on the left shows lengths of DNA (in red) forming a hollow tube that can pierce through a cell’s membrane, producing a man-made gateway or pore. Other fragments of DNA are assembled into a honeycomb-shaped cap, forming a ‘seal’ which locks the pore to the surface of the cell. This man-made channel (shown from three different perspectives in the microscope pictures on the right) might one day be used to conduct electrical impulses into our cells, possibly supplying power to other man-made devices working hard on the inside.

Written by John Ankers

—

Source: bpod.mrc.ac.uk

Tight Genes Vast amounts of genetic information are squeezed into the cells of every living creature. Even in E. coli bacteria, one of the simplest life-forms, DNA is compressed into coils and loops, creating a single, circular chromosome. If unravelled, it would be more than 1,000 times the length of the rod-shaped cell encasing it. Scientists recently identified a type of protein in E. coli that helps to compress the DNA. This computer simulation shows how molecules of this protein, known as MatP (shown in green, light blue, yellow and purple) attach themselves to a DNA molecule and help it maintain a looped shape. Experiments showed that in E.coli bacteria that lacked MatP, the DNA became less compressed and cell division was affected. Understanding more about the internal structure of bacteria may help in the development of drugs to fight infection. Written by Mick Warwicker — Maria Schumacher Duke University School of Medicine, USA Copyright Elsevier 2012 Published in Molecular Cell 48(4): 560-571
Pop-upView Separately

Tight Genes

Vast amounts of genetic information are squeezed into the cells of every living creature. Even in E. coli bacteria, one of the simplest life-forms, DNA is compressed into coils and loops, creating a single, circular chromosome. If unravelled, it would be more than 1,000 times the length of the rod-shaped cell encasing it. Scientists recently identified a type of protein in E. coli that helps to compress the DNA. This computer simulation shows how molecules of this protein, known as MatP (shown in green, light blue, yellow and purple) attach themselves to a DNA molecule and help it maintain a looped shape. Experiments showed that in E.coli bacteria that lacked MatP, the DNA became less compressed and cell division was affected. Understanding more about the internal structure of bacteria may help in the development of drugs to fight infection.

Written by Mick Warwicker

—

Published in Molecular Cell 48(4): 560-571

Source: bpod.mrc.ac.uk

DNA Bricks These nanoscale structures are made out of DNA – the molecule that resides in each nucleus of each cell in our bodies. But there is a difference. DNA in our cells exists as very long double-stranded helices. DNA used to build these shapes is in the form of short, single-strand DNA bricks, each with a unique computer-designed sequence allowing them to bind other bricks. Why would scientists use DNA to build nanoscale shapes, smiley faces and a space shuttle (bottom row, middle)? Although these particular shapes serve no purpose, the aim in building them was to show the versatility of possible DNA brick designs. Nanotechnologists could, in principle, use such bricks to build precise structures for encapsulating drugs to deliver to specific organs in the body, for controlling interactions between particular proteins in a cell, or for numerous other nanoscale applications. Written by Ruth Williams — Yonggang Ke Harvard University, USA Published in Science 338(6111): 1177-1183
Pop-upView Separately

DNA Bricks

These nanoscale structures are made out of DNA – the molecule that resides in each nucleus of each cell in our bodies. But there is a difference. DNA in our cells exists as very long double-stranded helices. DNA used to build these shapes is in the form of short, single-strand DNA bricks, each with a unique computer-designed sequence allowing them to bind other bricks. Why would scientists use DNA to build nanoscale shapes, smiley faces and a space shuttle (bottom row, middle)? Although these particular shapes serve no purpose, the aim in building them was to show the versatility of possible DNA brick designs. Nanotechnologists could, in principle, use such bricks to build precise structures for encapsulating drugs to deliver to specific organs in the body, for controlling interactions between particular proteins in a cell, or for numerous other nanoscale applications.

Written by Ruth Williams

—

Source: bpod.mrc.ac.uk

Growing Back From the time we are born until adulthood, most of our cells are growing. Their replication, movement and repair are all part of a major construction job that makes us what we are. But growth is also a difficult balance – unnecessary growth in certain tissues can lead to cancer, while a lack of growth in ‘settled’ or differentiated tissues can leave holes that might have mended easily during early development. Originally taken from the lining of a human throat, these cells have been treated with chemicals which coaxed them out of retirement, to start growing again. After a few days, the cells were turned back into ‘throat cells’ (outlined here in red with their DNA stained blue), simulating transplantation in another human body. They quickly ‘remembered’ to develop mucus proteins (shown in green) and a carpet of microscopic hairs called cilia (in white) which sweep dirt from human lungs. Written by John Ankers — Frank Suprynowicz Georgetown University Medical Center, USA Published in PNAS 109(49): 20035-20040
Pop-upView Separately

Growing Back

From the time we are born until adulthood, most of our cells are growing. Their replication, movement and repair are all part of a major construction job that makes us what we are. But growth is also a difficult balance – unnecessary growth in certain tissues can lead to cancer, while a lack of growth in ‘settled’ or differentiated tissues can leave holes that might have mended easily during early development. Originally taken from the lining of a human throat, these cells have been treated with chemicals which coaxed them out of retirement, to start growing again. After a few days, the cells were turned back into ‘throat cells’ (outlined here in red with their DNA stained blue), simulating transplantation in another human body. They quickly ‘remembered’ to develop mucus proteins (shown in green) and a carpet of microscopic hairs called cilia (in white) which sweep dirt from human lungs.

Written by John Ankers

—

Source: bpod.mrc.ac.uk