9th March 2020 4:16 pm

Science News – Issue 2

Genetic engineering revolutionizes the treatment of macular degeneration in the eye. Fig. 3 of the eye

Macular degeneration is the most common cause of blindness in developed countries. Some 300,000 cases are diagnoses every year in the UK. The condition is caused when a key protein at the back of the eye that protects the retina goes wrong Researches in Oxford, led by Professor ?, have developed an extraordinary way of treating this condition. They have engineered a healthy protein into a safe virus, injected this DNA into the back of the eye, so that the virus infects cells there, which make the corrected protein. Brilliant.

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Great Barrier Reef under attack

File:COTS_held_out_of_water.jpg

The Great Barrier Reef off the coast of Queensland, Australia is one of the wonders of the world. But it is under attack! Not only by humans this time, but also by the crown-of-thorns starfish, Acanthaster planci. The Australian Institute of Marine Science has carried out surveys, and found that there has been a 50% loss of coral between 1985 and 2012. Half caused by the starfish. Yes warmer water, human development and pollution have also caused damage. But these starfish actually eat the polyps of the coral, killing it. Amazingly the Australian government are investing £35 million to protect the reef from all of this attack. £5.7 million of this will be used to cull the starfish where divers will inject bile into hundreds of thousands of them. Quite a challenge.

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see this fantastic video – https://www.youtube.com/watch?v=-ardrFZuFkU

‘W’ to the rescue in bacterial attack

Colitis is a painful debilitating condition where the bowel becomes inflamed. One of the reasons for this is the overgrowth of some bacteria like E. Coli, which live in the gut without causing problems, until there are too many of them. Using antibiotics to kill them off sometimes works, but is a blunt weapon. The antibiotics kill many types of bacteria, some of which are the good guys, leaving the nasty ones to grow unopposed, and the delicate ecosystem of the colon is upset.

Scientists in Texas and California have used a property of the bad guys that is they respire in the very low oxygen environment using a Molybdenum dependent cofactor. To kill them off, the Molybdenum has been swopped with Tungsten, or ‘W’, and then the bugs can’t respire. This is very elegant. There is a possibility of an oral medicine which will reduce inflammation in the colon, by selectively and precisely hitting the bad bacteria. Furthermore it doesn’t affect the rest of the gut flora when there is no inflammation, leaving the good bacteria alone. Although the work has been done in mice, there is evidence it will work in humans. This is very important and exciting work but don’t try it as tungsten is very toxic so much more research is required before it is safe for humans.

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Precision editing of the gut microbiota ameliorates colitis. Zhu W., et al. Nature  553 (11th Jan) 2018 pp208-211

Bubbles: An exciting new way to look inside the gut.

The deep ocean, Saturn’s surface: inhospitable places very difficult to study. But what about closer to home? The core of our own large bowel is a very inhospitable, anaerobic place and difficult to study, especially in real time. There are many more microbial cells in the bowel than all the cells in the rest of the body. They are not randomly scattered but act as an ecosystem with constant battles for supremacy within their realm. Scientists at the California Institute of Technology have used ultrasound to detect microbes deep with in gut. The cells have been genetically engineered to express ‘acoustic reporter genes’. The bacteria make gas filled vesicles, bubbles, which can be detected by ultrasound. This is an exciting potential new way to study gut diseases and also to target tumours. A clever idea indeed.

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Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts. Bourdeau R W,  Lee-Gosselin A et al. Nature 553, 86–90 (04 January 2018) doi:10.1038/nature25021

Genetic engineering of firefly gene enables single cancer cells to be seen in a live animal. Fig. 4

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 – Fig.5

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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Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer     Cell Volume 172, Issue 4, p881–887.e7, 8 February 2018 Z Liu, Y Cai, et al. DOI: https://doi.org/10.1016/j.cell.2018.01.020

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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Dietary trehalose enhances virulence of epidemic Clostridium difficile. Collins C. Robinson et al   Nature volume 553, pages 291–294

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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Energy Utopia – Fusion Power

Is it possible to have pollution free, sustainable energy in unlimited quantities? There may be interesting geo-ethical consequences to this hypothetical situation but surely it is a goal worth pursuing. The potential answer is ‘Fusion Power’. Copying the sun, fusion between hydrogen elements to make helium releases massive amounts of energy. A key advance toward this goal was the invention of a new superconducting material; steel tape coated with a compound called yttrium-barium-copper oxide (YBCO). The energy is produced at extremely hot temperatures and magnetic fields will be used to contain the hot plasma. The technology builds on research at MIT but with large international collaboration, in particular ITER, a group currently building a facility in southern France.

Fusion energy is now potentially in reach. This could mean an unlimited carbon –free energy future. A big step forward is a collaboration between MIT in Cambridge MA and a new private company, Commonwealth Fusion Systems. The researchers predict the new magnets will be available within 3 years and production will happen within 15 years. ITER plan to begin producing fusion energy around 2035.

If MIT are involved, then it will probably happen.

Lassa fever in Nigeria, Good and bad news

The bad news is that Nigeria is suffering its worst outbreak of Lassa fever. Tragically, since the beginning of the year, the disease has killed over a hundred people, including brave healthcare workers. Lassa fever is caused by a virus of the Arenaviridae family. Many infected people get no symptoms but at the other end of the spectrum, like Ebola, symptoms include fever and bleeding from the mouth and GI tract. The death rate is about 25% of those detected.

But there is some good news. The public health reforms put in place since the 2014 Ebola outbreak in West Africa are working at full steam. Without them, the crisis would have been significantly worse.

The Nigeria Centre for Disease Control (NCDC) has become stronger, faster, and is better equipped. There are many more well trained staff who have access to sophisticated data-management tools which runs on smartphones, a great improvement on the previous pen and paper method. There are now four labs in Nigeria that can test for Lassa virus, cutting the diagnostic wait from four days to 24 hours.

There is human to human transfer of the virus but the reservoir of infection is in the rat. It is not known for certain yet why this outbreak is moving so fast. Researchers believe it is not the virus that is changing but the transmission from the rats. This view is supported as other rat borne diseases, e.g. monkey pox, are also increasing. It is also possible that the detection rate is dramatically improving due to education and the activities of the NCDC.

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Nigeria hit by unprecedented Lassa fever outbreak   Leslie Roberts et al. Science 16 Mar 2018: Vol. 359, Issue 6381, pp. 1201-1202 DOI: 10.1126/science.359.6381.1201