2016 Year of Innovation

C&I Issue 11, 2016

Motherless babies?

Fertilisation always starts with an egg, right? Well maybe not anymore, according to the results of a new landmark study in the journal Nature Communications in September (doi:10.1038/ncomms12676).

The scientists at the University of Bath have turned conventional wisdom on its head in creating baby mice by combining sperm with ‘haploid’ embryos that would otherwise lack the capability for further development. Strikingly, their findings suggest that any cell in the body could be fertilised by sperm – or even that babies could be born from two men without a mother.

The baby mice created developed normally and went on to produce their own litters, with three generations now produced by the same technique. Overall, 30 mouse pups were born with a success rate of 24%. While the haploid embryos used in the initial study were derived from mouse eggs, the researchers say any cell in the body could potentially be used if half the chromosomes are removed before they are fused with sperm.

In conventional mammal reproduction, the fertilising sperm triggers embryogenesis – embryo development – by inducing a calcium dependent event that also results in the death of the egg and sperm.

However, the researchers reported that haploid embryos injected with sperm undergo remodelling of chromosomal protein chromatin, possibly triggering genetic changes prompting development. Robin Lovell-Badge, group leader at The Francis Crick Institute, is quoted in the 14 September issue of The Daily Telegraph newspaper as saying the paper is ‘a technical tour de force’ that will yield insights into the importance of genetic reprogramming at these early steps of development. The technique could make it easier for women with cancer to have children, or allow other women to postpone having a family until later in life, as well as having implications for infertility treatment.

Alzheimer’s advance

In July, C&I reported on progress to develop a ‘universal vaccine’ for Alzheimer’s (2016, 7, 8). Created by researchers in the US and Australia, the vaccine platform is claimed as the first to target both abnormal proteins linked to the disease – inducing higher levels of antibodies against abnormal beta amyloid and tau proteins than in any previous studies (Scientific Reports, 2016, 6, article 28912). The antibodies generated bound strongly to beta amyloid and tau proteins in brain tissue from AD patients, with no adverse effects.

Around 7.5m new cases of AD are diagnosed every year. The vaccine platform relies on a type of white blood cell called memory T-cells usually generated after infection or immunisation. More T-cells are created as we age, so the team believes the vaccine may be especially valuable in the elderly. It could be useful for immunising patients at early stages of AD to slow progression – or even to immunise healthy people at risk of the disease, they report.

Top seeds

F1 hybrids are typically the most expensive varieties in seed catalogues. But an unusual method of natural cloning already used by some plants to reproduce their seeds could make them easier and cheaper to make, researchers reported in February (Current Biology, doi:10.1016/j.cub.2015.12.045). F1 hybrids are the result of crossing two pure plant lines to create new plants with the superior qualities of both parents, for example, heavy cropping, disease resistance, good vigour and high uniformity. The problem is that seeds from F1 hybrids can’t reproduce these superior qualities when crossed, which means new ones must be produced every year; that’s both costly and time-consuming.

However, the scientists at the John Innes Centre in Norwich, UK, reported creating hybrids of a type of daisy plant with the same biological characteristics as a F1 hybrid parent. This particular daisy species, mouse-ear hawkweed (Hieracium pilosella), is unusual as it reproduces asexually by ‘apomixis’ or cloning its seeds. Using apomixis, the researchers created 11 new hybrids and reproduced them for two generations through natural cloning of the seeds. Twenty different properties were assessed to see if they changed from one generation to the next. If developed as a reproductive switch, experts say apomixis could one day help farmers to propagate their own seeds.

Seeing good

Unlike ‘bad cholesterol’ that clogs up arteries, ‘good cholesterol’ unplugs them by removing plaques. Scientists at the University of Georgia, US, have previously created synthetic mimics of good cholesterol or high density lipoprotein (HDL) and demonstrated that they lowered levels of triglycerides in rats. In spring 2016, however, they reported going a step further by making HDL mimics also containing iron oxide – a contrast agent that allows the particles to be seen by MRI (C&I, 2016, 4, 10). In this way, the particles should act as molecular flags or indicators to detect the onset of plaque formation linked to possible heart attacks or strokes. The lab is now targeting its MRI active HDL mimics at macrophages – white blood cells that make up atherosclerotic plaques along with lipids and cholesterol. Imaging studies should allow them to follow the ability of the particles to treat and remove plaques.

Fire stopper

In February, C&I reported on a new fire-fighting foam claimed to extinguish flames 50 times better than water (2016, 2, 6). Made from silica nanoparticles, the foam was produced by researchers at ITMO University and research firm SOPOT in Russia.

On exposure to air, the foam transforms to a polymer network that adheres to burning objects, cooling them and preventing re-ignition (ACS Applied Materials & Interfaces, doi:10.1021/acsami.5b08653).

Tests showed it demonstrates an extinguishing efficiency 15 times higher than the current leading fire extinguishing agent, aqueous film-forming foam. And because the polymer is inorganic, the team claims it can resist temperatures above 1000°C, much higher than alternative organic foams that break down at ca 300°C.

Once the fire is extinguished, the foam can be destroyed by adding water – producing safe and ‘bioinert’ silica particles. The researchers believe it could be a good substitute for other fire-fighting agents based on perfluorinated surfactants, some of which are being restricted due to toxicity concerns.

Photosynthesis in reverse

The production of biofuels and biochemicals may become cheaper and easier following the discovery of a way to ‘dramatically accelerate’ breakdown of the plant polymer cellulose. Traditional cellulase enzymes break down cellulose by hydrolysis, while enzymes called lytic polysaccharide monooxygenases (LPMOs) from fungi catalyse an oxidation pathway (C&I, 2016, 5, 9).

In the presence of chlorophyll pigments from cyanobacteria and plants, LPMOs degraded cellulose to its constituent oligosaccharides roughly 20-fold faster, the researchers from Denmark reported in spring 2016 (Nature Communications, doi:10.1038/ncomms11134). That’s like putting the process of photosynthesis into reverse gear, say the University of Copenhagen researchers.

Chlorophyll pigments excited by sunlight donate electrons to LPMO, which in turn deploys this extra energy by forming free radical ions that go on to attack cellulose. Ascorbic acid replenishes the chlorophyll by a reduction process, so reaction can continue.

Sunburn sensor

Sunburn could soon be consigned to history after scientists have developed a sensor to alert wearers how long they’ve been out in the sun – and when they have likely had enough! The sensor is made by inkjet printing a suspension of TiO2, food dye and a polymer binder onto a single layer of paper. UV light activates TiO2, which in turn breaks down food dyes to cause a gradual shift in colour of the paper, researchers at the University of New South Wales in Australia reported in early summer (ACS Sensor, doi:10.1021/acssensors.6b00244). The best dye identified so far is Brilliant blue – used in ice creams and sweets and the liqueur blue curacao – as it degrades linearly with time. Blocking light with various UV filters changes the rate of paper discoloration, which means it can be calibrated to different skin types.

Targeted cancer therapy

Cancer immunotherapies have been hailed as a ‘game-changer’ for cancer treatments, demonstrating spectacular results in recent clinical trials. Immuno-oncology drugs work by directing the body’s immune or T-cells to target and destroy cancer cells. But even these treatments aren’t always precise enough because of the huge variety of cancer cell mutations, which change or ‘shape-shift’ as the disease advances. In March, however, an international team of scientists reported a discovery that could help them to identify and track all cancerous cells, even at the most advanced stages (Science, doi: 10.1126/science.aafl490).

The researchers - led by Sergio Quezada and Charles Swanton at University College, UK - analysed data from hundreds of patients from previous studies to find a set of common flags or antigens present on all tumour cells, from the earliest to the most advanced stages of the disease. The discovery is like finding the ‘kingpin’ at the root of the criminal activity, according to Quezada: ‘The weak spot in a patient’s tumour [that should allow us] to wipe out the problem for good.’

It demonstrates that the seeds of a tumour’s own destruction lie within the tumour itself, paving the way for therapies that target all cancer cells in a single swoop based on the disease’s genetic signature.

Scientists could also exploit this information, for example, to develop a vaccine to activate T-cells, or by harvesting, growing T-cells that recognise these common antigens in all cancer cells and then administering them back to patients.

Novel triterpenes

Triterpenes from plants are important intermediates for a wide range of compounds from pharmaceuticals, nutraceuticals and cosmetics to crop protection agents. But soon they could become even more valuable following the discovery of a new route to make them starting from new four-carbon ring scaffolds, rather than the usual five-carbon ring compounds, researchers reported last summer (PNAS, doi:10.1073/pnas.1605509113). The team at John Innes Centre in Norwich, UK, focused attention on an antifungal triterpene compound made by oats, which causes the roots of the plant to glow under UV light. They induced mutations in oat DNA to alter an enzyme called SAD1, involved in the first cyclisation step of triterpene synthesis. Instead of catalysing the production of the usual five-carbon rings, the mutated SAD1 enzyme resulted in four-carbon ring compounds. This mutated oat DNA gene was then expressed in yeasts and tobacco leaves to create a new family of terpenes – with potentially myriad more uses.

Smart dressing

Monitoring wounds to see whether they have become infected can be a painful and time-consuming process. To detect infection from burns or other patients, doctors currently have to remove the dressing, and wait for up to two days for test results.

In January, however, C&I reported on a new smart dressing that changes colour as soon as wounds become infected – (ACS Appl. Mater. Interfaces, doi:10.1021/acsami.5b07372).

Nanocapsules embedded in the dressing break open and release a fluorescent dye when they encounter toxic bacteria secreted by the wound.

The work was led by researchers at the University of Bath, UK, who have tested their prototype dressing to see how well it detects infection in swabs and blister fluid from burns patients from Bristol Children’s Hospital and Queen Victoria Hospital, West Sussex.

The team is commercialising the technology with healthcare company Hartmann and hopes to make it available in the clinic in around four years. One of the biggest benefits should be a reduction in the use of antibiotics, which are currently often administered as a precaution when infection is suspected.

DNA app store

The world’s first online app store for genetic information could be just around the corner, according to MIT Technology Review’s roundup of the ten breakthrough technologies in 2016 (www.technologyreview.com/s/600769/10-breakthrough-technologies). The development follows the creation of consumer genomics company Helix in 2015 by gene sequencing giant Illumina and investment firm Warburg Pincus.

Helix’s reported plan is to store thousands of gene sequences for every customer who sends in a sample of spit for analysis – say, for example, to find out whether or not they are at risk of a particular disease. By subsidising the cost of the initial genome analysis, the firm is said to be betting on the idea that others will want to tap into that information again later. A bit like the model for the Apple app store, media reports claim the goal is to make genetic analysis available to consumers for just a few dollars or so. MIT Technology Review notes that the powerhouse for the gene store is being built in San Diego, US, close to Illumina’s HQ, and should be capable of sequencing a million samples/year.

Hot solar cell

Solar energy is abundant, but current technologies to harness it for electricity generation are hugely inefficient. For a single-layer solar cell made of silicon – the type used in most modern panels – around 32% efficiency is the best that’s theoretically possible.

But researchers have now demonstrated technology that could surpass this so-called Shockley-Queisser Limit, and potentially double the amount of energy generated. In May, the team at Massachusetts Institute of Technology (MIT), US, published a paper in Nature Energy (doi:10.1038/NENERGY.2016.68) describing construction of a solar thermophotovoltaic device (STPV) with a higher solar-to-electrical conversion efficiency than the underlying PV cell.

The idea behind STPVs is to convert sunlight to heat before generating electrical power. To construct their device, the MIT team used carbon nanotubes capable of absorbing over the full solar spectrum, including wavelengths typically wasted as heat by PV cells. These were aligned with nanophotonic crystals, which can be made to emit precisely determined wavelengths of light when heated.

Heating the device to a temperature of 1000°C causes the crystals to continue to emit a narrow band of wavelengths of light that matches the band an adjacent PV cell can capture and convert to an electric current. In their demonstration, the team showed, for the first time, that their STPV system has a higher solar-to-electrical conversion efficiency – albeit a relatively modest 6.8% –compared with that of the underlying PV cell.

STPV technology could provide a way to use solar power around-the-clock as it should be relatively unaffected by brief changes in outdoor light levels such as a passing cloud.

See-through wood

Transparent wood could be the future window material of choice rather than glass, according to a report this autumn from scientists at the University of Maryland, US. The group’s wood composite window transmits around 92% of light, almost as much glass, while avoiding glare and so resulting in more uniform and consistent lighting, they reported in a paper in Advanced Materials (doi: 10.1002/adma.201600427).

Not only that, but wood is a better thermal insulator than glass – which should lead to saving on energy bills. The wood composite is made by first boiling wood in a solution of sodium hydroxide and Na2SO3 to remove lignin – as in paper production – and then soaking it in hydrogen peroxide, whereupon the colour changes from yellow to white.

Next, the de-lignified wood is filled with epoxy resin to reduce light scattering, leading to a transparent wood composite. Scientists in Sweden reported a transparent wood with 85% transmittance earlier in 2016 using a similar procedure (Biomacromolecules, doi: 10.1021/acs.biomac.6b00145).

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