10 May 2013 A Fishy Cancer Tale You may not think that tropical zebrafish can tell us a lot about testicular cancer in men, but the little creatures are proving a useful ally in the fight against the disease. This striking rosette is made up of chromosomes – long strings of DNA (stained blue) that twist up into neat packages as a cell divides. A protein called LRRC50, coloured green, coats the chromosomes, while their centres are labelled red. But while these chromosomes are taken from a human cell, LRRC50 is also found in zebrafish. Animals with a faulty version of the protein develop the fishy equivalent of testicular cancer, and LRRC50 faults are also found in some men affected by the disease. Although more than nine out of ten patients now survive testicular cancer the treatments are harsh, so studying LRRC50 in fish will help researchers develop kinder future therapies. Written by Kat Arney — Rachel Giles University Medical Center Utrecht, The Netherlands Originally published under a Creative Commons Attribution license Published in PLoS Genetics 9(4): e1003384
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10 May 2013

A Fishy Cancer Tale

You may not think that tropical zebrafish can tell us a lot about testicular cancer in men, but the little creatures are proving a useful ally in the fight against the disease. This striking rosette is made up of chromosomes – long strings of DNA (stained blue) that twist up into neat packages as a cell divides. A protein called LRRC50, coloured green, coats the chromosomes, while their centres are labelled red. But while these chromosomes are taken from a human cell, LRRC50 is also found in zebrafish. Animals with a faulty version of the protein develop the fishy equivalent of testicular cancer, and LRRC50 faults are also found in some men affected by the disease. Although more than nine out of ten patients now survive testicular cancer the treatments are harsh, so studying LRRC50 in fish will help researchers develop kinder future therapies.

Written by Kat Arney

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Eye Insights The eyes of fish grow larger throughout their lives because stem cells produce new tissue in the retina, the light-sensitive lining at the back of the eye. Humans and other mammals lack these stem cells, so the retina can neither grow nor be repaired naturally. Studies of zebrafish show that the development of stem cells in the retina is controlled by chemicals from nerve cells nearby. This research may lead to a better understanding of degenerative diseases of the eyes and nervous system in humans and the causes of cancer, which can occur when stem cells go out of control. Pictured is a cross-section of a zebrafish eye. The ring stained green with the dark centre is the lens, with the retina appearing as a semi-circle around it. Stem cells are concentrated in the regions at either end of the red-stained arcs of nerve connecting tissue. Written by Mick Warwicker — Kara Cerveny Zebrafish Research, UCL, London
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Eye Insights

The eyes of fish grow larger throughout their lives because stem cells produce new tissue in the retina, the light-sensitive lining at the back of the eye. Humans and other mammals lack these stem cells, so the retina can neither grow nor be repaired naturally. Studies of zebrafish show that the development of stem cells in the retina is controlled by chemicals from nerve cells nearby. This research may lead to a better understanding of degenerative diseases of the eyes and nervous system in humans and the causes of cancer, which can occur when stem cells go out of control. Pictured is a cross-section of a zebrafish eye. The ring stained green with the dark centre is the lens, with the retina appearing as a semi-circle around it. Stem cells are concentrated in the regions at either end of the red-stained arcs of nerve connecting tissue.

Written by Mick Warwicker

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Source: bpod.mrc.ac.uk

Muscle Mosaic Exercise may help tone our muscles, but their underlying strength depends on complex interactions between individual muscle fibres and an intricate protein ‘Velcro’ that connects muscle to tendons. If a vital piece of the protein mesh is missing or damaged, muscle is easily torn from its base and muscular dystrophy results. Scientists keen to combat muscular dystrophy have engineered zebrafish embryos to mimic the condition. Here, they used a technique called genetic mosaic analysis to graft normal (stained blue) and weak (red) zebrafish muscle fibres into normal muscle tissue (green). This mosaic of muscle allows mutant fibres to overcome their weakness and take the strain as the muscle contracts. Building a molecular picture of muscle structure and function is helping researchers identify ways to tackle inherited conditions like Duchenne’s muscular dystrophy that currently affects 1 in 3600 boys. Written by Caroline Cross — Clarissa Henry University of Maine, USA Originally published under Creative Commons (CC-BY) Published in PLOS Biology 10(10): e1001409
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Muscle Mosaic

Exercise may help tone our muscles, but their underlying strength depends on complex interactions between individual muscle fibres and an intricate protein ‘Velcro’ that connects muscle to tendons. If a vital piece of the protein mesh is missing or damaged, muscle is easily torn from its base and muscular dystrophy results. Scientists keen to combat muscular dystrophy have engineered zebrafish embryos to mimic the condition. Here, they used a technique called genetic mosaic analysis to graft normal (stained blue) and weak (red) zebrafish muscle fibres into normal muscle tissue (green). This mosaic of muscle allows mutant fibres to overcome their weakness and take the strain as the muscle contracts. Building a molecular picture of muscle structure and function is helping researchers identify ways to tackle inherited conditions like Duchenne’s muscular dystrophy that currently affects 1 in 3600 boys.

Written by Caroline Cross

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Source: bpod.mrc.ac.uk

Heartbeat During the scariest bit of the film, you feel a familiar pounding in your chest. Most of the time, however, our heartbeat goes unnoticed. To keep an adult human going the heart has to beat 60-80 times a minute – that’s over 100,000 times a day. This constant activity relies on a carefully choreographed pattern of electrical signals, produced by the movement of calcium ions. Now, using zebrafish genetically engineered to produce a calcium-sensitive fluorescent protein, scientists can watch as signals are conducted through its tube-shaped heart. When viewed under a microscope, computer software maps the fluorescent signals (white) through the beating heart. The red lines show how the electrical signal moves from right to left, marking its position every 60 milliseconds. This new approach to studying the heart could give important insights into various cardiac diseases, driving the development of better treatments. Written by Emma Stoye — Didier Stainier Department of Biochemistry and Biophysics, University of California San Francisco, USA Image originally published under Creative Commons Attribution License Published in PLOS Biology 6(5): e109
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Heartbeat

During the scariest bit of the film, you feel a familiar pounding in your chest. Most of the time, however, our heartbeat goes unnoticed. To keep an adult human going the heart has to beat 60-80 times a minute – that’s over 100,000 times a day. This constant activity relies on a carefully choreographed pattern of electrical signals, produced by the movement of calcium ions. Now, using zebrafish genetically engineered to produce a calcium-sensitive fluorescent protein, scientists can watch as signals are conducted through its tube-shaped heart. When viewed under a microscope, computer software maps the fluorescent signals (white) through the beating heart. The red lines show how the electrical signal moves from right to left, marking its position every 60 milliseconds. This new approach to studying the heart could give important insights into various cardiac diseases, driving the development of better treatments.

Written by Emma Stoye

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Source: bpod.mrc.ac.uk

Shady Behaviour As our eyes scan this page, the cells in our retinas are firing off messages. It takes them a split-second to convert this picture – of similar cells inside the retina of a zebrafish – into electrical signals bound for the brain. A high-powered microscope was used here to zoom in on a cross-section of the fish’s retina, highlighting the contours of different layers of cells. The sensitive photoreceptors (the layer of larger, bulky cells on the left) gather light from the outside world, converting it into an electrical signal that penetrates deeper into the retinal tissue (the layers of cells on the right). Meanwhile, the black-coloured, inky pigment cells absorb any excess light, protecting the photoreceptors from damage. Our eyes, it appears, have their own internal pair of sunglasses. Written by John Ankers — Rachel Macdonald and Steve Wilson UCL, UK
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Shady Behaviour

As our eyes scan this page, the cells in our retinas are firing off messages. It takes them a split-second to convert this picture – of similar cells inside the retina of a zebrafish – into electrical signals bound for the brain. A high-powered microscope was used here to zoom in on a cross-section of the fish’s retina, highlighting the contours of different layers of cells. The sensitive photoreceptors (the layer of larger, bulky cells on the left) gather light from the outside world, converting it into an electrical signal that penetrates deeper into the retinal tissue (the layers of cells on the right). Meanwhile, the black-coloured, inky pigment cells absorb any excess light, protecting the photoreceptors from damage. Our eyes, it appears, have their own internal pair of sunglasses.

Written by John Ankers

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Source: bpod.mrc.ac.uk

Aspirin Looks Fishy Researchers are gathering a growing pile of data showing that regular low doses of aspirin, a staple of medicine cabinets around the world for more than a century, can reduce the risk of several types of cancer. But nobody really knows how it works. In search of clues, scientists have turned to tiny transparent zebrafish larvae that have been genetically modified to develop skin cancer. The tumour is made up of cancerous cells (green outline) that have high levels of a molecular receptor called EP1 (stained magenta), which acts like a radio receiver. They receive a chemical signal called prostaglandin, which tells the cancer cells to grow. Aspirin turns off prostaglandin production by neighbouring immune cells (stained red), cutting off the ‘fuel supply’ and slowing tumour growth. Although they’re just a few millimetres long, these delicate fish larvae could hold the explanation for aspirin’s cancer-preventive effects on our own bodies. Written by Kat Arney — Paul Martin School of Biochemistry, University of Bristol Copyright Elsevier 2012 Published in Current Biology (In Press)
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Aspirin Looks Fishy

Researchers are gathering a growing pile of data showing that regular low doses of aspirin, a staple of medicine cabinets around the world for more than a century, can reduce the risk of several types of cancer. But nobody really knows how it works. In search of clues, scientists have turned to tiny transparent zebrafish larvae that have been genetically modified to develop skin cancer. The tumour is made up of cancerous cells (green outline) that have high levels of a molecular receptor called EP1 (stained magenta), which acts like a radio receiver. They receive a chemical signal called prostaglandin, which tells the cancer cells to grow. Aspirin turns off prostaglandin production by neighbouring immune cells (stained red), cutting off the ‘fuel supply’ and slowing tumour growth. Although they’re just a few millimetres long, these delicate fish larvae could hold the explanation for aspirin’s cancer-preventive effects on our own bodies.

Written by Kat Arney

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Published in Current Biology (In Press)

Source: bpod.mrc.ac.uk

Accessing Ancestry Outward appearances would suggest fish have little in common with humans. But if we look beyond the scales at the underlying skeleton there is much to be learnt. Zebrafish and humans, though separated by millions of years of evolution, share a large number of similar genes. This includes a group of genes that code for an enzyme called exostosin. If these genes are faulty in humans they develop a bone disorder called hereditary multiple exostoses (HME). Sufferers are often short in stature and develop numerous bone tumours. Zebrafish with a similar genetic error show the same kinds of defects, including shorter bones. Skull bones (stained blue) are stubby (right) compared to those of normal fish (left). Probing these faulty fish could provide clues as to what goes wrong in the one in 50,000 people who have HME. Written by Lux Fatimathas — Henry H. Roehl MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, UK Originally published under Creative Commons (CC-BY 2.0) Published in PLoS Genetics 4(7)
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Accessing Ancestry

Outward appearances would suggest fish have little in common with humans. But if we look beyond the scales at the underlying skeleton there is much to be learnt. Zebrafish and humans, though separated by millions of years of evolution, share a large number of similar genes. This includes a group of genes that code for an enzyme called exostosin. If these genes are faulty in humans they develop a bone disorder called hereditary multiple exostoses (HME). Sufferers are often short in stature and develop numerous bone tumours. Zebrafish with a similar genetic error show the same kinds of defects, including shorter bones. Skull bones (stained blue) are stubby (right) compared to those of normal fish (left). Probing these faulty fish could provide clues as to what goes wrong in the one in 50,000 people who have HME.

Written by Lux Fatimathas

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Source: bpod.mrc.ac.uk