Science News February 2018
Genetic engineering of firefly gene enables single cancer cells to be seen in a live animal.
Bioluminescence is the emission of light from living organisms1,2. The genes that code from their light emitting proteins have revolutionised clinical diagnosis and biomedical research, and amazingly have created several billion dollar markets. The firefly luciferase gene can be used to light up cancer cells in live animals. A drug that kills the cancer cells then causes the light to go out. A famous Japanese group have used genetic engineering to markedly improve the use of cancer cells expressing firefly luciferase in whole animals for drug discovery. They used an ingenious combination of a chemically modified luciferin and a genetically selected luciferase, which clearly results in a large increase in light emission, when used in live animals. They claim they can now detect single cells in a live mouse. The apparent higher expression of genetically engineered bioluminescent proteins may be caused by an increase in half life of the protein, rather than higher synthesis3-5. This half-life can be as short as 20 minutes in cells. Luciferases and jellyfish photoproteins, such as those from the marine species Gaussia, Aequorea and Obelia, use coelenterazine as the luciferin1,2,6. This produces blue light, and is more sensitively detected by an intensified CCD camera, than the yellow or red emission from firefly luciferase1,2. The EM- CCD camera used by these authors is likely to be red sensitive. This is an important point. A further issue is the quantum yield, the fraction of luciferin molecules producing a photon. Natural firefly luciferase has a very high quantum yield, typically 80-100%1. The combination of a genetically engineered luciferase and modified luciferin may have reduced this. In coelenterazine systems this is typically <20%. The high quality work reported here will lead to further application of bioluminescence in whole animals, where it is superior to fluorescence.
- Campbell,AK. (1988). Chemiluminescence: principles and applications in biology and medicine, pp608. Horwood/VCH, Chichester and Weinheim.
- Campbell AK (2017). Fundamentals of intracellular calcium, pp 428, Wiley, Chichester.
- Badminton, M, Kendall, JM, Sala-Newby, G and Campbell AK (1995). Differences in stability of recombinant apoaequorin within subcellular compartments. Biochem. Biophys. Res. Commun. 217:950-957.
- Jeffery, J. Kendall, J.M. and Campbell, A.K. (2000). Apoaequorin monitors degradation of endoplasmic reticulum (ER) proteins initiated by loss of ER Ca2+. Biochem. Biophys. Res. Commun. 268,711-715.
- Baubet,V, Le Mouellic, H, Campbell, AK, Lucas-Meunier, E, Fossier, P and Brulet, P (2000). Chimeric GFP-aequorin as bioluminescent Ca2+ reporters at the single cell level. Proc.Natl.Acad.Sci.97:7260-7265.
- Campbell,AK and Herring,PJ. (1990) Marine Biology 104:219-225. Imidazolopyrazine bioluminescence in copepods and other marine animals.
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Iwano et al, Science 359, 935-939 (2018). Single –cell bioluminescence imaging of deep tissue in freely moving animals.
Space Travel – time to dream again
A cherry red Tesla Roadster with a dummy at the wheel, and the sound system playing Bowie’s ‘Space Oddity’, went into space this month. It was launched by the Falcon Heavy rocket, the brainchild of Elon Musk, a visionary genius. Musk set up SpaceX a private company, in 2002 to open up space travel. He had many doubters. But it’s not just the technical wizardry that is so important here. He has given a new generation inspiration, excitement and a chance to dream again about Space travel. Pity about the car though. The dummy hopefully enjoyed the ride.
Stop press: Monkeys cloned
Two baby macaque monkeys, Zhong Zhong and Hua Hua, have been born in Shanghai, China. The crazy thing is that they are truly identical, made from cloning using SCNT, Somatic Cell Nuclear Transfer. Dolly the sheep was the first mammal cloned and this has now been achieved in 23 mammalian species. But this is the first time in a primate. The researchers argue that monkeys are needed to study human disease mechanisms, genetic defects and potential therapeutic treatments. The technology used to achieve these live births is very clever but the regulation of use of the technology and the ethics will no doubt be debated long and hard.
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Clever Clostridium, naïve nutritionists: Another sorry sugar tale
In 2000/2001 a sugar, trehalose was granted safe status in the USA and Europe, and because technological advances made it cheap to make, was added to many foods. Shortly after this, epidemics of serious severe diarrhoea started, caused by the pathogen, Clostridium difficile. Trehalose is a disaccharide that is made of two sugar units, in this case, two glucoses. Surely this cannot cause problems?
Take a clue from nature. The human body evolved coping well with mainly sucrose (glucose and fructose) maltose (glucose and glucose) and babies are very good at metabolising lactose (galactose and glucose). The way the two sugar units link together and the sterioisomerism of the molecules is vital. In the right place, trehalose is an amazing disaccharide that is used by bees for rapid energy and by plants to withstand dehydration, but the human gut has not been exposed to much of it. Two strains of Clostridium difficle have evolved to flourish in very low levels of trehalose. The arguments made by the researchers from the USA, Netherlands and UK are compelling. The moral? Why change the sugars we eat. They are not benign molecules to be messed with.
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Reversal of the Earth’s magnetic field
Is this a doomsday scenario?
Everyone who uses a compass knows that the Earth has a magnetic field around it produced by the molten metal at the core of our planet. The compact needle points towards magnetic North, which is different from geographic North. Scientists have discovered that, every hundred thousand years or so, the filed turns upside down. In other words, it reverses. Recent data from satellites obtained by the European Space Agency (ESA) has shown that the next reversal has already started. Some have argued that a complete reversal could be catastrophic, and allow a lethal stream of particles from the sun, and cosmic rays. But NASA says we do not need to worry as the fossil record from times when this occurred before shows that life carried on as normal.
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