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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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
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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

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Source: bpod.mrc.ac.uk

Fashionable DNA As if billowing in the breeze, this picture shows a piece of flapping fabric made almost entirely from human DNA. Roughly 20,000 times smaller than a shirt on a washing line, it was stitched together by a series of chemical reactions. Strips of tightly connected DNA molecules – called DNA nanotubes (highlighted in red and green here) – were strung together along thinner, flexible strands of DNA, giving the material a secret ability. Another chemical reaction locks the nanotubes in place like stuck slats in a window blind, instantly turning a draping cloth into a firm platform or support. Such shape-shifting fabrics might be just the thing to inject back into human bodies as biodegradable scaffolding to help our tissues repair. With many more important uses to explore for this DNA-based material, we’re unlikely to get around to making jeans out of genes any time soon. Written by John Ankers — Omar Saleh University of California, Santa Barbara, USA Published in PNAS 109(43): 17342-17347 
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Fashionable DNA

As if billowing in the breeze, this picture shows a piece of flapping fabric made almost entirely from human DNA. Roughly 20,000 times smaller than a shirt on a washing line, it was stitched together by a series of chemical reactions. Strips of tightly connected DNA molecules – called DNA nanotubes (highlighted in red and green here) – were strung together along thinner, flexible strands of DNA, giving the material a secret ability. Another chemical reaction locks the nanotubes in place like stuck slats in a window blind, instantly turning a draping cloth into a firm platform or support. Such shape-shifting fabrics might be just the thing to inject back into human bodies as biodegradable scaffolding to help our tissues repair. With many more important uses to explore for this DNA-based material, we’re unlikely to get around to making jeans out of genes any time soon.

Written by John Ankers

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Source: bpod.mrc.ac.uk

Sex Change On the whole, it is widely accepted that mammals with a Y chromosome are male. However, recent research has produced an exception to the rule. Knocking out a single gene in mice can turn males into females. Researchers breeding a strain of mutant mice lacking a stress-response molecule, namely Gadd45g, wondered why litters produced mainly female pups. Upon closer inspection, they discovered that many of the offspring were in fact genetically male, although they lacked male gonads (shown top left), so looked like females (top right). The researchers discovered that Gadd45g is normally expressed in the same regions of the embryo as Sry, a gene on the Y chromosome known to direct the development of male gonads in the embryo. Evidently without Gadd45g, Sry can’t trigger male gonad development, and female genitalia result. The work uncovers an important piece to the jigsaw of molecular sex determination. Written by Brona McVittie — Christof Niehrs Institute of Molecular Biology, Germany Copyright Elsevier 2012 Published in Developmental Cell 23(5): 1032-1042
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Sex Change

On the whole, it is widely accepted that mammals with a Y chromosome are male. However, recent research has produced an exception to the rule. Knocking out a single gene in mice can turn males into females. Researchers breeding a strain of mutant mice lacking a stress-response molecule, namely Gadd45g, wondered why litters produced mainly female pups. Upon closer inspection, they discovered that many of the offspring were in fact genetically male, although they lacked male gonads (shown top left), so looked like females (top right). The researchers discovered that Gadd45g is normally expressed in the same regions of the embryo as Sry, a gene on the Y chromosome known to direct the development of male gonads in the embryo. Evidently without Gadd45g, Sry can’t trigger male gonad development, and female genitalia result. The work uncovers an important piece to the jigsaw of molecular sex determination.

Written by Brona McVittie

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Published in Developmental Cell 23(5): 1032-1042

Source: bpod.mrc.ac.uk

Leap Frogging Sheep Cloning hit the big screen with Jurassic Park’s rampaging dinosaurs. In fact it had already been achieved on their amphibian cousins thirty years earlier. In 1962, recent Nobel prize winner John Gurdon cloned a tadpole by replacing the DNA of an unfertilised frog egg with that of an adult frog’s gut cell. Decades later scientists, including the late Keith Campbell, applying the same principle cloned the first sheep. A sheep breast cell provided the adult DNA and that’s how she got the name Dolly – after busty country singer Dolly Parton. This year, Peng Peng the first genetically modified sheep, was cloned. Peng Peng was tweaked to produce more unsaturated fats, potentially producing healthier meat. Cloning technology continues to develop, but Jurassic Park is likely to remain fictional. Recent findings show even the best-kept DNA would only last about seven million years, leaving 65-million-year-old dinosaur DNA well past its expiry date. Written by Lux Fatimathas — Image originally published under Creative Commons (CC BY-NC 2.0); Courtesy of Jon Sullivan
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Leap Frogging Sheep

Cloning hit the big screen with Jurassic Park’s rampaging dinosaurs. In fact it had already been achieved on their amphibian cousins thirty years earlier. In 1962, recent Nobel prize winner John Gurdon cloned a tadpole by replacing the DNA of an unfertilised frog egg with that of an adult frog’s gut cell. Decades later scientists, including the late Keith Campbell, applying the same principle cloned the first sheep. A sheep breast cell provided the adult DNA and that’s how she got the name Dolly – after busty country singer Dolly Parton. This year, Peng Peng the first genetically modified sheep, was cloned. Peng Peng was tweaked to produce more unsaturated fats, potentially producing healthier meat. Cloning technology continues to develop, but Jurassic Park is likely to remain fictional. Recent findings show even the best-kept DNA would only last about seven million years, leaving 65-million-year-old dinosaur DNA well past its expiry date.

Written by Lux Fatimathas

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  • Image originally published under Creative Commons (CC BY-NC 2.0); Courtesy of Jon Sullivan

Source: bpod.mrc.ac.uk

Sticky Subject For most people, misbehaving mucus causes nothing more than a blocked nose. However, for cystic fibrosis sufferers, overly-thick, sticky mucus is the cause of a constant battle against lung infection. A defective CFTR gene is to blame – the protein it codes for disintegrates before it can reach where it’s needed to create normal mucus. But there is hope. By putting a special genetic fragment alongside the human CFTR gene and inserting them into the genome of a healthy mouse, human CFTR protein can occur in the right place. Animals with this genetic modification have high concentrations of the protein in the tips of cells lining the nose (stained orange in the top image), whereas cells in mice without the fragment (bottom image) do not. This raises the possibility of eventually using the gene fragment as a gene therapy for the 60,000 cystic fibrosis sufferers worldwide. Written by Jan Piotrowski — Lawrence Ostrowski UNC School of Medicine, USA Courtesy of Lawrence Ostrowski Published in Gene Therapy
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Sticky Subject

For most people, misbehaving mucus causes nothing more than a blocked nose. However, for cystic fibrosis sufferers, overly-thick, sticky mucus is the cause of a constant battle against lung infection. A defective CFTR gene is to blame – the protein it codes for disintegrates before it can reach where it’s needed to create normal mucus. But there is hope. By putting a special genetic fragment alongside the human CFTR gene and inserting them into the genome of a healthy mouse, human CFTR protein can occur in the right place. Animals with this genetic modification have high concentrations of the protein in the tips of cells lining the nose (stained orange in the top image), whereas cells in mice without the fragment (bottom image) do not. This raises the possibility of eventually using the gene fragment as a gene therapy for the 60,000 cystic fibrosis sufferers worldwide.

Written by Jan Piotrowski

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Source: bpod.mrc.ac.uk

Signs of Ageing As we grow old white hairs begin to sprout up, our skin wrinkles and invisible changes occur deep inside our cells. Ageing brings wear and tear to our epigenetic machinery - the chemical scaffolding built alongside our DNA which turns genes on or off. This chart compares the strings of genes – the genomes - of a new-born baby, a 26-year-old and a 103-year-old. Epigenetic machinery (coloured dark blue here) surrounds a large portion of the young baby’s genome (the inner circle). This machinery controls the fine balance of genes switched on during early development and drops away (shown as a lighter shade of blue) as we progress through our 20s (middle circle) towards old age (outer circle). Learning more about how epigenetic control is lost with age might allow scientists to pinpoint the genes that increase the risk of cancer in later in life. Written by John Ankers — Manel Esteller Cancer Epigenetics and Biology Program, Bellvitge Institute for Biomedical Research Published in PNAS 109(26): 10522-10527 
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Signs of Ageing

As we grow old white hairs begin to sprout up, our skin wrinkles and invisible changes occur deep inside our cells. Ageing brings wear and tear to our epigenetic machinery - the chemical scaffolding built alongside our DNA which turns genes on or off. This chart compares the strings of genes – the genomes - of a new-born baby, a 26-year-old and a 103-year-old. Epigenetic machinery (coloured dark blue here) surrounds a large portion of the young baby’s genome (the inner circle). This machinery controls the fine balance of genes switched on during early development and drops away (shown as a lighter shade of blue) as we progress through our 20s (middle circle) towards old age (outer circle). Learning more about how epigenetic control is lost with age might allow scientists to pinpoint the genes that increase the risk of cancer in later in life.

Written by John Ankers

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Source: bit.ly

Bad Batteries Our cells are fuelled by tiny ‘batteries’ called mitochondria (pictured), home to the energy-generating biochemistry that facilitates our existence. Every mitochondrion in our body is copied from those present in the egg from which we developed. Tracing this all the way back to the dawn of man, scientists reason that all such structures in today’s population must have descended from a ‘mitochondrial Eve’. In addition to the genome inside the cell nucleus, mitochondria harbour small sets of genes. Recent research in fruit flies demonstrates that mutations in mitochondrial genes affect the expression of hundreds of nuclear genes in the male, but not the female reproductive tissues. And a more recent study shows that variation in mitochondrial genomes affects ageing in male flies. Could this explain why men tend to die younger than women? Written by Brona McVittie — Copyright Science Photo Library Any re-use of this image must be authorised by Science Photo Library Research published in Current Biology 2012
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Bad Batteries

Our cells are fuelled by tiny ‘batteries’ called mitochondria (pictured), home to the energy-generating biochemistry that facilitates our existence. Every mitochondrion in our body is copied from those present in the egg from which we developed. Tracing this all the way back to the dawn of man, scientists reason that all such structures in today’s population must have descended from a ‘mitochondrial Eve’. In addition to the genome inside the cell nucleus, mitochondria harbour small sets of genes. Recent research in fruit flies demonstrates that mutations in mitochondrial genes affect the expression of hundreds of nuclear genes in the male, but not the female reproductive tissues. And a more recent study shows that variation in mitochondrial genomes affects ageing in male flies. Could this explain why men tend to die younger than women?

Written by Brona McVittie

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Source: bpod.mrc.ac.uk

New Beats Skin and bones can heal themselves, but broken hearts are not so easily mended. Our heart is made up of two types of cells, fibroblasts for structure and muscle cells that do the beating. After a heart attack, muscle cells die and, in a struggle to repair the damage, fibroblasts multiply. But they make the heart tissue thicker and less flexible, imperilling the vital pump even further. Now, researchers studying mouse heart cells (pictured), have found that adding proteins which activate certain genes can turn fibroblasts into beating muscle cells (dyed red). What’s more, these converted cells integrate into existing heart muscle. And they form new junctions with existing cells (green bands), which means they can all beat in unison. This discovery brings hope for new ways to treat damaged hearts. Written by Sarah McLusky — Jose Cabrera Eric N. Olson, University of Texas Southwestern Medical Center Reprinted by permission from Macmillan Publishers Ltd: Nature, Copyright 2012 Published in Nature
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New Beats

Skin and bones can heal themselves, but broken hearts are not so easily mended. Our heart is made up of two types of cells, fibroblasts for structure and muscle cells that do the beating. After a heart attack, muscle cells die and, in a struggle to repair the damage, fibroblasts multiply. But they make the heart tissue thicker and less flexible, imperilling the vital pump even further. Now, researchers studying mouse heart cells (pictured), have found that adding proteins which activate certain genes can turn fibroblasts into beating muscle cells (dyed red). What’s more, these converted cells integrate into existing heart muscle. And they form new junctions with existing cells (green bands), which means they can all beat in unison. This discovery brings hope for new ways to treat damaged hearts.

Written by Sarah McLusky

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Source: bpod.mrc.ac.uk

Wheel of Fate Animals develop according to a programed pattern – they follow one line from head to tail, and another from back to belly. In fruit fly embryos this pattern of development is orchestrated by a protein called dorsal, which switches certain genes on and off. Dorsal levels are spread unevenly around the embryo’s girth. The amount determines which genes are expressed where, which in turn dictates the fate of new cells. This embryo cross section shows the system at work. Each colour represents a different gene. At the top, where there is least dorsal protein, a gene called dpp (stained yellow) is turned on. At the bottom, high concentrations of dorsal switch on another gene (red). So this fluorescent pinwheel helps scientists understand how the right sorts of cells end up in the right place. Written by Daniel Cossins — Angelike Stathopoulos California Institute of Technology, USA Copyright Elsevier 2012 Published in Developmental Cell
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Wheel of Fate

Animals develop according to a programed pattern – they follow one line from head to tail, and another from back to belly. In fruit fly embryos this pattern of development is orchestrated by a protein called dorsal, which switches certain genes on and off. Dorsal levels are spread unevenly around the embryo’s girth. The amount determines which genes are expressed where, which in turn dictates the fate of new cells. This embryo cross section shows the system at work. Each colour represents a different gene. At the top, where there is least dorsal protein, a gene called dpp (stained yellow) is turned on. At the bottom, high concentrations of dorsal switch on another gene (red). So this fluorescent pinwheel helps scientists understand how the right sorts of cells end up in the right place.

Written by Daniel Cossins

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Source: bpod.mrc.ac.uk