Scientists Engineer E.Coli to Produce Key Precursor of Spandex

The Future: Bacteria Produced Hot Pants?

Scientists from the company Genomica have genetically engineered E.Coli to produce 1,4-Butanediol (BDO), a key chemical in the production of Spandex, clothing of choice for superheroes, glam rockers and 80’s disco enthusiasts.

The work, published in the journal Nature Chemical Biology, has the potential to drastically change the way BDO is produced. Currently one million metric tons are produced per year and all of this is derived from oil and natural gas. Almost half of the BDO produced globally is dehydrated to produce Tetrahydrofuran. This can then be polymerised to polytetramethylene oxide, the primary use of which is in fibres such as spandex.

The researchers faced several challenges whilst trying to produce their engineered bacteria. The first of which being identifying a synthesis mechanism, as there is no known naturally occurring biological synthesis pathway for BDO. Instead they had to compute all potential pathways from the typical E. coli metabolites to BDO. The computer algorithm they used  identified over 10,000 four-six step pathways that could result in synthesis of BDO from common metabolites, including acetyl-CoA, succinyl-CoA and glutamate.

These methods were then narrowed down based on theoretical yield, pathway length and thermodynamic feasibility. After this they picked out the following pathway as the best way for E.Coli to produce BDO:

The BDO synthesis pathway. Each number indicates an enzyme: (1) 2-oxoglutarate decarboxylase; (2) succinyl-CoA synthetase; (3) CoA-dependent succinate semialdehyde dehydrogenase; (4) 4-hydroxybutyrate dehydrogenase; (5) 4-hydroxybutyryl-CoA transferase; (6) 4-hydroxybutyryl-CoA reductase; (7) alcohol dehydrogenase. Steps 2 and 7 occur naturally in E. coli, whereas the others are encoded by heterologous genes introduced in this work.

With an elucidated pathway, then came the challenge of how to get a bacterium to carry it out. Not all the enzymes required for the pathway are present in the wildtype E.Coli. As a result of this, the group identified several different mechanisms for generating the intermediate 4-Hydroxybulymate (4HB) settling on; the addition of three genes sucCD (E. coli), sucD and 4hbd (P. gingivalis).

The final stage in the process, 4HB to BDO, also required some manipulation. The change requires two reduction steps, catalyzed by dehydrogenases. This can occur by the addition of exogenous 4HB to wild-type Clostridium acetobutylicum. However, for efficient production they needed to have the process contained within E.Coli. So instead  they expressed the 4-hydroxybutyryl-CoA transferase (cat2) gene from P. gingivalis for the conversion of 4HB to 4HB-CoA. The final stages then involved the action of  4-hydroxybutyryl-CoA reductase and the native alcohol dehydrogenase, finally resulting in a viable BDO product.

Whilst this discovery does not directly result in the production of spandex or other useful fibres by bacteria. This could prove to be an efficient and environmentally friendly way to produce crime-fighting and disco outfits at some point in the future!

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Viral Science: New Caledonian Crow – Not So Bird Brained

Behavioural Ecology Research Group © Simon Walker

The New Caledonian Crow is a remarkably smart species of bird. They are the “only non-human species with a record of inventing new tools by modifying existing ones, then passing these innovations to other individuals in the cultural group”

This weeks viral science video part of research carried out by the Behavioural Ecology Research group in Oxford . This video below is the first time these birds were presented with this challenge:

p.s. apologies for the lack of posts recently, I shall return to regular blogging shortly.

The Sound of Science: Results & Explanation

First of all a big thank you to everyone who took part in this little experiment. Secondly, sorry this post is a little later than I originally said it would be.

I was inspired to try this after listening to the sound and reading about what its effects should be. I was surprised to find that it’s effects worked on me, but I was curious as to whether that was the placebo effect because I knew what was supposed to happen. So that was the motivation for the experiment. The results were very interesting, 21 votes were recorded and were as follows:

What Effect Did the Sound Have On You?

None – 6 – 29%

Made me feel energised – 8 – 38%

Made me feel strange – 6 – 29%

Made me feel sleepy – 1 – 5%

But, what was the sound? Well, this experiment looked at the effects of binaural beats. An EEG detects different frequency waves in the brain during different mental states. The theory of binaural beats is that by listening to a particular frequency the brain enters the state of mind corresponding tp the EEG , as below:

> 40 Hz	Gamma waves	Higher mental activity, including perception, problem solving, fear, and consciousness
13–39 Hz	Beta waves	Active, busy or anxious thinking and active concentration, arousal, cognition, and or paranoia
7–13 Hz	Alpha waves	Relaxation (while awake), pre-sleep and pre-wake drowsiness, REM sleep, Dreams
4–7 Hz	Theta waves	deep meditation/relaxation, NREM sleep
< 4 Hz	Delta waves	Deep dreamless sleep, loss of body awareness

The sound in the experiment was a Theta wave. Therefore, should have created feelings of being tired  and sleepiness. The poll on my original post found very different results with feeling “energised” the most popular feeling due to the sound and feeling “sleepy” the least popular.

This is obviously not a 100% accurate study. I have no idea how long the people who voted listened for, what they listened with (supposedly headphones makes the effect much more pronounced) or what environment they were in. As a result, with a small sample size and these big unknowns the inverse of the expected results is, ironically, not unexpected!

There have been lots of suggested (and unproven) uses and effects of binaural beats including improving memory, sporting performance, stopping smoking, dieting help and tackling erectile dysfunction. Some have even referred to it as an “auditory alternative medicine”! Even more bizarrely some people are claiming that this technology can be used to create drug like effects known as “i-dosing”. The effects of these sounds are still being studied and their actual effects is hotly debated with some maintaining that it is all placebo.

To me, without being able to find sufficient research on the effects of the sounds, I find it hard to draw a conclusion about the effects. I am willing to accept that binaural sounds may have a real effect on alertness. However, the more outlandish claims are really just ridiculous, and should be ignored.

To see an alarmist US news report on “i-doping” watch this video (sorry about the poor syncing of the audio):

Giant Penguin Discovered in Peru

A more unusual example of penguin plumage

This was originally posted on the I,Science Blog

The dulcet tones of Morgan Freeman and the journey of the Emperor penguins warmed the hearts of millions following the release of March of the Penguins. However, the evolutionary trail of the species is equally as interesting.

A new study, published in the journal Science, tells of the discovery of a ‘Giant Penguin’ fossil discovery with implications for our knowledge of the ancestry of the penguin. Found in Peru, the 5ft specimen shows several plumage features present in modern day penguins.

Known as Inkayacu paracasensis, or Water King, it lived in the late Eocene period, approximately 36 million years ago.  The study was led by Julian Clarke of the University of Texas who said, “Before this fossil, we had no evidence about the feathers, colours and flipper shapes of ancient penguins.”

Despite several differences between the fossil, affectionately named “Pedro”, and its modern descendents the shapes of the flippers and feathers have helped to identify the passage of the common penguin from being bird with flight to being able to travel in a medium 800 times more dense and 70 times more viscous than air.

However, this isnt the only time that a ‘Giant penguin’ discovery has been reported. In 1948 several people reported observing a 15ft penguin first on Clearwater Beach, Florida then further affleild. Sightings reported included  zoologist Ivan T. Sanderson who theorised that it had been somehow driven away from its natural habitat. It was later revealed that ‘Giant Penguin Hoax’ was a prank with the original sightings faked and the following sightings either observer error or more faked reports. For more faked penguin discoveries this video by the BBC is well worth a watch.

Teen Rebellion Mapped in the Brain

A new study carried out at the University of Pittsburgh has indicated what might be the cause of teenagers risky behaviour.

The research, published in the Journal of Neuroscience, involved observing the brains of adolescent and mature rats during a reward activity. The team led by Bita Moghaddam used electrodes to show brain cell activity. They found that the brains of the adolescent mice reacted with a great deal more excitement that the mature adult brains (as seen below in Figure 1). This increased stimulation was observed along with a loss of organisation of brain cell function.

 

Figure 1: A graph showing the increase or decrease of neuronal firing during the reward activity (each line represents a neuron)

It is believed that this could be the reason why teenagers show an increased level of  rash behavior, addiction, and mental diseases. This was enforced y the results seen when the researchers investigated the orbitofrontal cortex, a region thought to weigh up payoffs and punishments in decision making.

“The disorganized and excess excitatory activity we saw in this part of the brain means that reward and other stimuli are processed differently by adolescents,” Moghaddam said. “This could intensify the effect of reward on decision-making and answer several questions regarding adolescent behaviour, from their greater susceptibility to substance abuse to their more extreme reactions to pleasurable and upsetting experiences.”

Whilst this study may give potential a chemical reason why teenagers are prone to poor judgement, it is unlikely that blaming the orbitofrontal cortex is likely to work as an excuse!

Source:

Moghaddam et al (2011). Reduced Neuronal Inhibition and Coordination of Adolescent Prefrontal Cortex during Motivated Behavior. J Neuro. 31(4):1471-1478

Top 5 Science Fails – 5: David Lyall, Tibbles and the Stephens Island Wren

Science has done a lot for us as a society, without it we would be still be in the middle ages, I would not be sat here able to write this and could possibly be considered to be a wise old man approaching the end of his life! However, despite the advances, there have been a few faux pas and amusing accidents along the way and I am gong to write a top 5 and post up one each day. I should first of all say that I am only considering science that was originally intended to be beneficial and failed and am not intending to demean or trivialise any of the serious mistakes science has made ( e.g. biological warfare, the nuclear bomb etc.).  So here we go……

5: David Lyall, Tibbles and the Stephens Island Wren

Now this story is disputed, some claim it to be hearsay and legend, whilst others stick to it faithfully. However, evidence seems to indicate that it is true to a certain extent. So I am going to tell the story as, if it is true, it definately deserves a place on this list.

In 1894 a light house was constructed on Stephens Island (part of New Zealand). The story goes that a cat named ‘Tibbles’ travelled to the Island along with the construction crew and David Lyall who was to be the lighthouse keeper and was also a keen biologist.

After some time on the Island Lyall noticed that Tibbles was bringing back small birds to the light house. He sent off a few samples to a friend in London to find out what the bird was as he did not recognise it. It was discovered to be a new species, and the only flightless perching bird in the world. They began to prepare for publication in a popular journal and Lyall sent off more of Tibbles’ hunt to eminent scientists.

However, one day there were no more birds being deposited at the lighthouse. Tibbles had wiped out the entire species. It is the only recorded case in history of a single organism causing the extinction of a whole species.

Of the 15 recorded specimens of the bird, 3 currently reside in the Natural History Museum in London, whilst the whereabouts of 5 are currently unknown.

An artists impression of the Stephens Island Wren

Tomorrow I will post up number 4……

Source:

QI Series 2 Episode 2

Father Christmas’ Amazing Journey

I originally wrote this article for Biomed Central’s ‘The Word’:

Millions of children all across the world wait up on Christmas Eve hoping to hear the patter of hoof prints, a distant deep and rich laugh. However, what are the ‘scientific’ practicalities of Father Christmas’ annual road trip?

If he visits all 700,000,000 Christian children in the world it is estimated he would have to travel 212 million miles. Now whilst this might cause a pretty hefty devaluation of your car if it appeared on your milometer, it presents a different set of problems for ‘Jolly Ol’ St Nick’.

One such problem is the weight of his present stash. If every child was given a Transformers toy weighing 659g his total load would be about 460,000 metric tonnes. A typical reindeer is able to pull approximately 150kg. This means that he would require around 3 million friends for Rudolf! Given the typical reindeer will eat 2.1% of its body weight a day in the winter St Nick will need to produce almost 230 million carrots in his allotment to feed them for just the Christmas Eve journey.

Now the question that it is prudent to pose when considering this is the amount of energy these Reindeer will need to produce. The total weight of Santa’s entourage requires a lot of force to reach the 1,800 miles per second needed to deliver all his presents within the Christmas Eve window, 700 quintillion joules of energy to be precise. However, the problem with this is that it assumes that he is travelling outside of the earth’s atmosphere with zero air resistance or drag. The process of reentering the earth’s atmosphere is the most difficult stage in his long journey, as the most likely occurrence is that the reindeer, presents, sleigh and all would rapidly disintegrate due to the heat.

But then again maybe it’s just magic!

Some of the data in this article was from this article in the Telegraph: http://bit.ly/i8Tc89

For more Christmassy fun here is a Science Christmas poem some coursemates and I created: http://bit.ly/fSyr39

Flightless Females Brings Hope For Future

A new technique which renders female mosquitoes flightless has been put forward at a novel control mechanism for Dengue Fever.

Dengue fever, or ‘Bone Crusher disease’ as it has been named, is a tropical disease with 50-100 million reported cases each year. The World Health Organisation claims 40% of the world’s population are now at risk from the disease. It is carried by yellow fever mosquitoes and transmitted through the anti-blood clotting saliva injected during a females bite.

It causes headaches, severe muscle and joint pains as well as shock and haematological effects. There is no treatment currently in use and the disease is managed through treating the symptoms, although there have been some promising developments in recent years.

Along with the problem of treatment there are few effective environmentally friendly control methods for Dengue fever. There is a reliance on pesticides, which can be very harmful to the natural environment.

This new technique works by genetically altering male mosquitoes to possess a gene that will result in any female offspring having disrupted wing muscle development. By doing this, it is hoped that the yellow fever mosquito population will be under control within 6-9 months of implementation.

The discovery was made when it was observed that a region of DNA coding for ‘Mosquito Actin 4’ was found highly concentrated in the indirect flight muscles of the female larvae and of low abundance in males. Gametes were then constructed to have lethal genes fused to the Actin 4 gene, which in adults results in the death of cells where Actin 4 is programmed to be present. The fusion gene was also made to be dominant to the natural form of the gene so that it is successfully inherited by future generations.

In the above image a red fluorescent tag has been attached to the lethal fusion gene and it can be seen in high density in the wing muscle area of females

In the wild, this technology could be implemented by placing the genetically mutated males in fresh water lake. Once hatched the males will fly off and seek a mate. As they will only seek to mate with a female yellow fever it is a very specific treatment. Once mating has occurred and the eggs have matured the female will lay her eggs. They will hatch and the males will fly away. Due to the genetic mutation, the females will be unable to do so and will die resulting in them being unable to transmit Dengue fever.

Whilst this is a promising technique, it remains to be seen whether it will be successfully employed. If it is implemented then the theory could be adapted for other species of mosquito, to target other conditions such as malaria.

Reference:

Female-specific flightless phenotype for mosquito control; Anthony A. James et al; PNAS; 22/02/2010