Category: Genetic modification

Engineering mosquito gut bacteria to fight malaria

By Ed Yong | July 16, 2012 3:00 pm

A malarial mosquito is a flying factory for Plasmodium – a parasite that fills its guts, and storms the blood of every person it bites. By hosting and spreading these parasites, mosquitoes kill 1.2 million people every year.

But Plasmodium isn’t the only thing living inside a mosquito’s guts. Just as our bowels are home to trillions of bacteria, mosquitoes also carry their own microscopic menageries. Now, Sibao Wang from Johns Hopkins Bloomberg School of Public Health has transformed one of these bacterial associates into the latest recruit in our war against malaria. By loading it with genes that destroy malarial parasites, Wang has turned the friend of our enemy into our friend.

Many groups of scientists have tried to beat malaria by genetically modifying the species of mosquito that carries it – Anopheles gambiae. Marcelo Jacobs-Lorena, who led Wang’s new study, has been at the forefront of these efforts. In 2002, his team loaded mosquitoes with a modified gene so that their guts produce a substance that kills off Plasmodium.

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Genetically engineered silkworms with spider genes spin super-strong silk

By Ed Yong | January 3, 2012 9:00 am

In a lab at the University of Wyoming, some silkworms are spinning cocoons of silk, just as every silkworm has done for millions of years. But these insects are special. They have been genetically engineered to spin a hybrid material that’s partly their own silk, and partly that of a spider. With spider DNA at their disposal, they can weave fibres that are unusually strong and tough. It’s the latest step in a decades-long quest to produce artificial spider silk.

Spider silk is a remarkable material, wonderfully adapted for trapping, crushing, climbing and more. It is extraordinarily strong and tough, while still being elastic enough to stretch several times its original length. Indeed, the toughest biological material ever found is the record-breaking silk of the Darwin’s bark spider. It’s 10 times tougher than Kevlar, and the basis of webs that can span rivers.

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Without some basic science, GM mosquitoes won't bite

By Ed Yong | November 14, 2011 4:49 pm

There have been several stories recently about genetically modified mosquitoes, bred for the purpose of fighting diseases like malaria and dengue fever. These are exciting, sophisticated techniques, but in a new piece for Slate, I argue that they’re being let down by the fact that we still don’t know a lot about basic mosquito biology, like thier mating behaviour. Ecology may not be as sexy as tinkering with genes, but history teaches us that it’s vital if these approaches are to work.

Here’s a taster; head to Slate for more.

But all of these recent attempts to turn mosquitoes into malaria- and dengue-killing machines have something in common: The modified mosquitoes need to have lots of sex to spread their altered genes through the wild population. They must live long enough to become sexually active, and they have to compete successfully for mates with their wild peers. And that is a problem, because we still know surprisingly little about the behavior and ecology of mosquitoes, especially the males. How far do they travel? What separates the Casanovas from the sexual failures. What affects their odds of survival in the wild? How should you breed the growing mosquitoes to make them sexier? Big question marks hang over these seemingly straightforward questions.

Heather Ferguson from the University of Glasgow studies mosquito ecology. She views the knowledge gap in this field as a significant obstacle that stands in the way of the GM-mosquito initiatives. History tells us how dismally such initiatives can fare if they are not constructed on solid ecological foundations. In the 1970s and 1980s, several groups tried to control the mosquito population by releasing sterile males that would engage females in fruitless sex. The vast majority of the experiments failed.

Their poor performance is often blamed on the fact that the males were sterilized with damaging doses of radiation. But they had many other disadvantages. Lab-bred mosquitoes are frequently reared in large, dense groups, which produces smaller, less competitive individuals. The artificial lights of a lab could also entrain their body clocks to the wrong daily rhythms, driving them to search for mates at the wrong time of the day. And in several cases, the modified males ignored the wild mosquitoes and preferred to mate with their lab-reared kin instead. These problems went unnoticed in lab tests, where the modified mosquitoes were compared with unaltered ones that had been raised in the same conditions. They seemed to be perfectly competitive, but they proved to be feeble challengers to their wild peers.

Picture by James Gathany

Hacking the genome with a MAGE and a CAGE

By Ed Yong | July 14, 2011 4:00 pm

It couldn’t be easier to make sweeping edits on a computer document. If I were so inclined, I could find every instance of the word “genome” in this article and replace it with the word “cake”. Now, a team of scientists from Harvard Medical School and MIT have found a way to do similar trick with DNA. Geneticists have long been able to edit individual genes, but this group has developed a way of rewriting DNA en masse, turning the entire genome of a bacterium into an “editable and evolvable template”.

Their success was possible because the same genetic code underlies all life. The code is written in the four letters (nucleotides) that chain together to form DNA: A, C, G and T. Every set of three letters (or ‘codon’) corresponds to a different amino acid, the building blocks of proteins. For example, GCA codes for alanine; TGT means cysteine. The chain of letters is translated into a chain of amino acids until you get to a ‘stop codon’. These special triplets act as full stops that indicate when a protein is finished.

This code is virtually the same in every gene on the planet. In every human, tree and bacterium, the same codons correspond to the same amino acids, with only minor variations. The code also includes a lot of redundancy. Four DNA letters can be arranged into 64 possible triplets, which are assigned to only 20 amino acids and one stop codon. So for example, GCT, GCA, GCC and GCG all code for alanine. And these surplus codons provide enough wiggle room for geneticists to play around with.

Farren Isaacs, Peter Carr and Harris Wang have started to replace every instance of TAG with TAA in the genome of the common gut bacterium Escherichia coli. Both are stop codons, so there’s no noticeable difference to the bacterium – it’s like replacing every word in a document with a synonym. But to the team, the genome-wide swap will eventually free up one of the 64 triplets in the genetic code. And that opens up many possible applications.

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Gene therapy saves patient from lifetime of blood transfusions

By Ed Yong | September 15, 2010 1:00 pm

Gene_therapyThe patient known as P2 is just 18 years old, but he has been receiving monthly blood transfusions since the age of 3. P2 has a genetic disorder called beta-thalassaemia. Thanks to a double whammy of faulty genes, he can’t produce working versions of haemoglobin, the protein that allows red blood cells to carry oxygen around the body. Regular transfusions were the only things that kept him alive but for the last 21 months, he hasn’t needed them.

An international team of scientists have managed to partially correct his genetic faults, granting him his independence. It’s a major victory for gene therapy, the act of editing faulty genes within living cells in order to treat diseases.

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Genes from Arctic bacteria used to create new vaccines

By Ed Yong | July 12, 2010 3:00 pm

Colwellia

Walk among the Arctic ice and you’ll sometimes encounter distinctive patches of red snow. They’re caused by a species of bacteria called Colwellia psycherythraea. It’s a cold specialist – a cryophile – that can swim and grow in extreme subzero temperatures where most other bacteria would struggle to survive. Colwellia’s cold-tolerating genes allow it to thrive in the Arctic, but Barry Duplantis from the University of Victoria wants to use them in human medicine, as the basis of the next generation of anti-bacterial vaccines.

Colwellia’s fondness for cold comes at a price – it dies at temperatures that most other bacteria cope with easily. By shoving Colwellia genes into bacteria that cause human diseases, Duplantis managed to transfer this temperature sensitivity, creating strains that died at human body temperature. When he injected these heat-sensitive bacteria into mice, they perished, but not before alerting the immune system and triggering a defensive response that protected the mice against later assaults. The Colwellia genes transformed another species of bacteria from a cause of disease into a vaccine against it.

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Unintentional genetic engineering – grafted plants trade genes

By Ed Yong | May 1, 2009 8:30 am

Blogging on Peer-Reviewed ResearchFor centuries, farmers have been genetically modifying their plants without even knowing it. That’s the message from German scientists who found that grafting, a common technique used to fuse parts of two plants together, causes the two halves to swap genes with each other.

Grafting can involve fusing the stem of one plant (the scion) to the roots of another (the stock), or a dormant bud to another stem. There are many reasons for this – sometimes it’s the most cost-effective way of cultivating the scion, sometimes the stock has properties that the scion lacks including hardiness or sturdiness. The vessels of the two halves eventually merge but people have long believed that they keep their genetic material to themselves. It turns out they were wrong.

Sandra Stegemann and Ralph Bock from the Max-Planck Institute tested the theory by grafting two strains of genetically engineered tobacco plant. A Samsun NN strain had its main genome loaded with a gene that produced a glowing yellow protein, and another that made the plant resistant to the antibiotic kanamycin. The second Petit Havana strain was engineered to produce a glowing green protein, and be resistant to spectinomycin, another antibiotic. These genes were shoved into the genome of its chloroplast, the small structures that allow plant cells to photosynthesise and that contain their own separate genetic material.

Once the plants had merged, Stegemann and Bock found that the point of fusion was rife with cells that produced both glowing proteins and shrugged off both antibiotics. They cut slices from the plant and grew them in liquid that contained both kanamycin and spectinomycin for a month. While chunks that were taken from other parts of the plant fared poorly under these conditions, many of those from the graft site thrived, even producing fresh shoots.

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The effect of GM crops on local insect life

By Ed Yong | April 19, 2009 10:00 am

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Blogging on Peer-Reviewed ResearchA large study weighs up the existing evidence on the impact of GM crops on local insect life, providing some much-needed scientific rigour to the GM debate.

In Europe, the ‘GM debate‘ about the merits and dangers of genetically-modified (GM) crops is a particularly heated one. There is a sense of unease about the power of modern genetic technology, and a gut feeling that scientists are ‘playing God‘. These discontents are stoked by the anti-GM camp, who describe GM crops with laden and fear-mongering bits of unspeak like ‘Frankenstein foods‘ and ‘unnatural’.

Bt cotton is better for non-targeted insects than non-resistant crops sprayed with insecticdes.In a debate so fuelled by emotion and personal values, scientific research and a critical analysis of the evidence rarely gets a look-in. But science has to grudgingly admit some blame in this, because there is actually precious little research on the safety of GM crops. And many of the studies that have been done were short-term and poorly replicated.

A lack of research is dangerous. It provides opening for people on either side of the debate to quote single, small studies as canon and brushing aside any research that contrasts with their stances.

Michelle Marvier and colleagues from Santa Clara University, California, are trying to change all that. They have analysed over 42 field experiments on GM crops to get an overall picture about their safety. The technique they used is called meta-analysis, a statistical tool that asks “What does everyone think?” It works on the basis that individual small studies may be far from conclusive, but pooling their results together can lead to stronger and more accurate results.

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Genetically-modified mosquitoes fight malaria by outcompeting normal ones

By Ed Yong | October 21, 2008 10:00 am

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Blogging on Peer-Reviewed ResearchFighting malaria with mosquitoes seems like an bizarrely ironic strategy but it’s exactly what many scientists are trying to do. Malaria kills one to three million people every year, most of whom are children. Many strategies for controlling it naturally focus on ways of killing the mosquitoes that spread it, stopping them from biting humans, or getting rid of their breeding grounds.

anophelesgambiaemosquito.jpgBut the mosquitoes themselves are not the real problem. They are merely carriers for the true cause of malaria – a parasite called Plasmodium. It suits neither mosquitoes nor humans to be infected with Plasmodium, and by helping them resist it, we may inadvertently help ourselves. With the power of modern genetics and molecular biology, scientists have produced strains of genetically engineered mosquitoes that cannot transmit the malarial parasite.

These ‘GM-mosquitoes’ carry a modified gene – a transgene – that produces chemicals which interfere with Plasmodium‘s development. Rather than being suitable carriers, the bodies of the modified mosquitoes spell death for any invading Plasmodium.

But scientists can’t very well change the genes of every mosquito in the tropics. To actually reduce the burden of malaria, the genetic changes that induce malaria resistance need to be spread throughout the mosquito population. The easiest way to do this is, of course, to let the insects do it themselves. And Mauro Marrelli and colleagues from the Johns Hopkins University have found that they are more than up to the task.

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How to turn cotton into a food crop

By Ed Yong | October 1, 2008 10:00 am

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Blogging on Peer-Reviewed ResearchThe world is currently home to 6.5 billion people and over the next 50 years, this number is set to grow by 50%. With this massive planetary overcrowding, Band Aid’s plea to feed the world seems increasingly unlikely. Current food crops seem unequal to the task, but scientists at Texas University may have developed a solution, a secret ace up our sleeves – cotton.

Cotton.JPGCotton is famed for its use in clothes-making and has been grown for this purpose for over seven millennia. We do not think of it as a potential source of food, and for good reason. The seeds of the cotton plant are rife with a potent poison called gossypol that attacks both the heart and liver. Only the multi-chambered stomachs of cattle and other hooved animals can cope with this poison, relegating cottonseed to a role as animal feed.

Getting rid of gossypol could contribute towards reducing the world’s hunger crisis. A fifth of a cottonseed’s weight is made up of oil, and a quarter of high-quality protein, and for every kilogram of fibre, each cotton plant produces 1.65 kg of seed. The plant is a worldwide crop, grown in over 80 countries by some 20 million farmers, the majority of whom live in the poorest parts of the world where starvation is an ever-looming threat. If only the seeds could be made edible.

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