Model Organisms

For my research into RNA metabolism I work on yeast, S. Cerivisiae; when I tell people this  I’m often asked why I’m not using human cells for my experiments which, my inquisitor believes, would be much more medically useful.

I think this is a common misconception, which stems from non-biologists not realising the connectedness of different life forms. Indeed, Sarah Palin enraged and amused the global scientific community in equal measure a few years back when she used the tale of Parisian geneticists studying fruitflies as an example of how scientists waste the public’s money.

But of course it’s important – as I have said many times – that the public understand why we scientists do the things we do with their money.  So with that in mind I’ve come up with a clever little analogy that you can use next time you’re round at your Nan’s house to explain why we use simple model organisms like yeast to gain an insight which will be useful to medical science.

Imagine you want to learn how a car works and you have access to two cars: a shiny new Mini made by BMW and one of those lovely old reliable classic Minis. You may have guessed that the new Mini represents the advanced human cell and the much loved old Mini the humble yeast.

Now to find out how the car works you are allowed to open the bonnet and tinker away, this is like a molecular biologist who deletes genes or pulls proteins out of the cell to see what they do.  So you open the new Mini up and see some shiny chrome and a lot of black plastic, it all looks a bit boring and you really can’t see how it might work or even how you might start taking it apart to figure out what it does. Now you look in the old Mini, it’s dirty but you can see wires, tubes and things that move when you turn the engine on.

So it’s clear to see which one will be easiest to start mucking around with to find out what all those bits do. The refined Mini made by BMW doesn’t like being played with, its engine is too complicated and inaccessible and all the moving bits are hidden away. The old mini however can be bashed around and is simply built, meaning you can tell what each part does relatively easily. Equally, playing with the old Mini is cheaper and you have more tools at your disposal thanks to the scrap yard! 

Now you know how the old Mini works: what a carburettor looks like and what the transmission is for. Through tinkering with an easily manipulable model you not only know how an old Mini works but a lot of what you’ve learnt can be applied to any car.

What you’ve learnt about the old Mini now informs how you approach finding out how the new Mini works, you come across the carburettor, which you know it is because it looks like the carburettor in the old Mini, you don’t need to pull it out – which as we have said is very difficult in a modern car – to see what it does because you’re already done that in the old car.

So you can see how studying a simpler, more manipulable version of what you’re really interested in can be advantageous to the researcher. Of course this is all possible because the Mini’s are both cars and yeast and human cells are both eukaryotes (one of the three classes of life forms on earth) and therefore share huge similarities which allow us to make generalisations of function and mechanisms.

Vitamin D to treat respiratory diseases?

 

Kathryn Vaughan

Research from a team in Australia has made a new link between Vitamin D and lung disease.

A deficiency in vitamin D is associated with many diseases, including rickets, but it has also been implicated in the pathogenesis of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), whereby it has been suggested that vitamin D deficiency reduces lung function.

Vitamin D is mainly involved in calcium homeostasis (the concentration of calcium in the bloodstream). This is why deficiencies in vitamin D are commonly associated with bone disorders.

It has been suggested that a vitamin D deficiency can reduce lung function, thus associating the vitamin deficiency with respiratory diseases. Dr Graeme Zosky, a senior lecturer in Child Health Research, headed a research group from Western Australia, to determine what effect, if any, a deficiency of vitamin D has on the lung.

A vitamin D deficient mouse model, developed by modification of their diet, was used and compared with mice that were not deficient in vitamin D, i.e. wild-type control mice. Measurements in lung volume, lung structure and lung function were assessed to determine if there were any differences relating to vitamin D deficiency.

Differences were found in both the lung size and lung volume of the mice. Vitamin D deficient mice had substantially reduced lung size compared to controls, suggesting altered lung growth, and this correlated with reductions in the thoracic gas volume measurement. In relation to the reduction in lung volume the mechanics of the lung were also affected in vitamin D deficient mice.

The researchers conclude from this investigation that “vitamin D deficiency causes deficits in lung function which are primarily explained by differences in lung volume” and “may explain the association between obstructive lung disease and vitamin D status”.  The results therefore may have important implications for the prevention/treatment of respiratory diseases in those with vitamin D deficiencies.

 

Zosky et al (2011) Vitamin D deficiency causes deficits in lung function and alters lung structure. American Journal of Respiratory and Critical Care Medicine, ahead of print.

The paper can be found at:

http://ajrccm.atsjournals.org/cgi/reprint/201010-1596OCv1?maxtoshow=&hits=10&RESULTFORMAT=&author1=zosky&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Spaghetti provides inspiration for a new treatment for spinal cord injury

Matt Farley

Researchers at the University of Milan-Biccoca in Italy have developed a new method to repair damaged spinal cords, after being inspired by spaghetti. Named the ‘bucatini project’ after the hollow pasta of the same name, the results suggest that the technique may be used in the future to treat people with paraplegia.

One of the major hindrances in the healing of damaged spinal cords is the formation of fluid-filled cysts, which impair the development of new nerve and blood cells at the site of the injury. Fabrizio Gelain is just one of many researchers around the world investigating ways to ‘bridge’ over these cysts.

Gelain’s team developed small hollow tubes made from biodegradable plastics which were around 3 millimetres long and could be implanted into areas of damage. The tubes were coated in small peptides, which anchored new cells around the tubes – effectively making them more ‘sticky’ and able to grab onto any new cells. “These tubes provide the reference points for the cells, and tissue starts to build up” says Gelain’s colleague, Angelo Vescovi.

Bundles of these tubes were implanted directly into the cysts of rats which had damaged spinal cords, paralysing their hind legs. A gel containing natural growth factors to stimulate nerve cell growth was also added.

After six months, new nerve cells and blood vessels were seen to have grown all the way across the treated areas, along with other types of ‘supporting cells’ which are vital for maintenance of the nerve fibres. The rats also regained some mobility in their hind legs, which was not seen in the untreated control rats.

What is unsure is whether the new nerve cells are successfully growing into the spinal column at the other end of the cyst, which is required for significant regeneration of the spinal column. Gelain intends to carry out further experiments to determine whether the new cells are making all the necessary connections.

The paper that accompanied this research is available online:

Gelain, F et al. 2011. Transplantation of Nanostructured Composite Scaffolds Results in the Regeneration of Chronically Injured Spinal Cords. ACS Nano 5, pp227-236

Fluorescent probes make nerves glow during surgery

 

Claire Tree-Booker

Scientists at the San Diego School of Medicine, University of California have developed fluorescent protein fragments, also known as peptides, which specifically label nerves. It is hoped this new technology will help surgeons avoid damaging nerves during surgery.

Accidental damage to nerves during surgery can cause many problems including pain, numbness and even paralysis.

The scientists report, in the 6 February 2011 edition of Nature Biotechnology, that when the fluorescent peptides were injected into mice, nerves were labelled within two hours; this created a ten-fold contrast compared to other body tissues, allowing the nerves to be easily seen.

The fluorescent labelling was found to have no effect on the activity of the nerves or the animals’ behaviour.

Whilst surgeons can identify nerves by their appearance or by electrical stimulation, they can sometimes be missed if they are buried or have a different appearance.  Dr Quyen T. Nguyen, carrying out the study, said “if surgery is required in the setting of trauma or infection, the affected nerves might not look as they normally would, or their location may be distorted”.

 “We have yet to test the peptide in patients, but we have shown that the fluorescent probe also labels nerves in human tissue samples”, says Nguyen.

Damaged nerves were also fluorescently labelled, suggesting that this technique could be useful in nerve repair surgery in the future.

The paper can be found at http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1764.html

Finding out what makes you, you.

Although Genetics is often seen as just another jigsaw piece making up the wide subject of Biology, it really underlies the whole study.

After all, is the most fundamental question of life not how does the set of chemicals inside us provide our every essence? How are those chemicals changed from simple molecules to everything that makes up a human being?

One thing which makes Genetics so interesting is that not even the best geneticists in the world can fully answer these questions. It is still a science very much in its infancy and early stages of understanding. After all, it was only around sixty years ago that James Watson and Francis Crick made the discovery of the structure of the DNA double helix. What is most fascinating about how these men made their discovery is that they came to their final theory of the double helix without any experiments of their own; they simply brought together other people’s evidence and used it to their advantage to gain their own final answer.

The less molecular side of Genetics which most people have heard something of is that of Gregor Mendel’s pea plant experiments: he performed genetic crosses with the plants, noting parent and offspring characteristics. As far back as 1856, he laid the foundations of what remain the basic principles of Genetics in these modern times. Mendel introduced the theory of recessive and dominant characteristics, without fully understanding what he was proposing.

A gene, in simplified terms, is a stretch of DNA coding for a characteristic in an organism. Allele is the word used when there are two or more different forms of a gene, so there can be different alleles for a particular gene. These different alleles can be classed as recessive or dominant, which basically do as their names suggest i.e. genes come in stronger or weaker forms; dominant being stronger and recessive being weaker. This means that one allele can dominate over the other and if both alleles occur, the so-called dominant allele will be shown. Since we have two copies of every gene, one from our mother and one from our father, any allele combination can occur. Therefore for a gene with two alleles, A (dominant) and a (recessive), there are three different allele couplets which could occur: AA, Aa or aa. This is called the organism’s genotype, the genes contained within its cells. The organism’s genotype produces a particular phenotype, which is the characteristic shown by an organism due to its genotype. For instance, in Mendel’s pea plant experiment, he found that yellow colour is dominant to green colour in the peas – yellow colour could be shown by the allele Y and green colour can be shown by the allele y. This means that in this case, the pea plant can have the genotypes of YY or Yy which will show a yellow phenotype, or yy which will show a green phenotype.

New ancestor to modern humans found in Siberia

Jamie Kendrick

Scientists have discovered that the exceptionally preserved finger bone found in Denisova Cave in the Altai Mountains of southern Siberia belongs to a distinct group of ancient human-like individuals that roamed the Asian continent alongside modern humans and the Neanderthals.

The study also showed that the Denisovans – the ancient group’s assigned name – probably interbred with an ‘Out of Africa’ migrating population of our own species and are responsible for an estimated 4-6% of the genome (entire DNA) of modern day Melanesians.

The revelations, published in articles in Nature, have transformed common knowledge of the relationships of our own species Homo sapiens and have yet again updated the continually growing tree of human evolution.

Dr Ian Tattersall, curator at the American Museum of Natural History, New York said, “the evidence is accumulating that the human evolutionary tree is quite luxuriantly branching. There were multiple species that competed in the evolutionary arena.”

Only 7 months after it was confirmed that Neanderthal DNA survives in present day Europeans, this outstanding new research has come to light to provide more evidence of our human ancestor’s involvement in interbreeding.

The finger bone, initially discovered in 2008 alongside body ornaments such as a bracelet and modern tools including microblades, was used to extract DNA for analytical tests by Professor Svente Pääbo’s team at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Results show that the individual to whom the bone pertains was female and possessed DNA and an evolutionary history significantly distinct from ourselves and the Neanderthals. The Denisovan group to which the female ‘X-woman’ belongs shared a common ancestor with the Neanderthals and modern humans H. sapiens around 1 million years ago (MYA).

The Denisovan DNA diverged first from the H. sapiens lineage about 800 thousand years ago (KYA) and again 640 KYA from their Neanderthal sister group to create the family tree shown below.

Comparing the DNA from modern humans of diverse ethnicities with samples from Neanderthals and Denisovans reveals the connection between modern day Melanesians and X-woman’s group that is interpreted as a classic signature of interbreeding.

Professor Chris Stringer from the Natural History Museum in London hailed the discovery as “nothing short of sensational” and described the Denisovans as a “new lineage of humans in Asia which we can relate to a particular group of people alive today.”

A tooth uncovered in the same cave back in 2000 was also found to contain DNA remarkably similar to that from the finger bone indicating that it derives from a shared population now dubbed the ‘Denisovans’ who inhabited Asia to an unknown range.

Dr David Reich from Harvard Medical School suggested that “these populations must have been spread across thousands and thousands of miles.”

The tooth possesses distinguishable features outside the variation and unlike anything seen in either our own species or the Neanderthals, prompting claims of a new species.

However, the authors chose against speculating on the exciting subject of whether the Denisovans constitute a new archaic human species, although Johannes Krause a member of Pääbo’s team commented that “the evidence is already very strong that we are looking at a previously unknown hominin, and possibly a new species.”

 

The research and information presented in this article can be found in -
Reich, D et al. 2010. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, pp 105

The Nuclear Debate

We can see from the last article that Nuclear power has proven to be an attractive path to take in order to counteract the issues presented by the depletion of non-renewables. I was intending to present the cons of Nuclear power in this article, however I recently attended a three day conference in Buxton during which a debate was held discussing the positives and negatives of nuclear power and I felt this would be a perfect article to place to tie between the pros and cons, therefore the cons article would shortly follow this. The debate was lead by two very knowledgable, highly trained individuals holding very high positions in the nuclear industry.  This was Mr.P.Wilkinson and Prof.G.Butler, below is an overview of both their contributions to the nuclear and environmental industry:


Supporting Nuclear Power:
 

Gregg Butler

Deputy Chief Executive, BNFL

Leader of a change management programme at the UK nuclear fuel manufacture Springfields site

Negotiated a complex £4Bn fixed price deal with Scottish Nuclear, now part of British Energy

Developed and patented, on behalf of BNFL, a method of density control for uranium oxide nuclear fuel, still in worldwide use. 

Director, UK Nirex

Member of the Radioactive Waste Management Advisory Committee (RWMAC)

Managing Director, Pangea Resources Australia Pty Ltd

Chairman, Westlakes Scientific Consulting



Opposing Nuclear Power:


Peter Wilkinson

Co-founder of Friends of the Earth and Greenpeace UK

Campaigns Director Greenpeace UK

Member of the original Board of Greenpeace International

Antarctic expedition leader over six years

Member of the Sizewell Site Stakeholder Group, reviewing and providing informed challenges to the operations on and plans for the Sizewell site.

 Member of the HSE Transition Advisory Group

We were able to ask several questions, however I have condensed the main issues covered and summarised the answers, the discussion was highly informative and very entertaining at times, especially when certain people got a bit carried away and were practically told to ‘shut up’.

The first issue addressed was the suitability of nuclear energy as an actual solution for the UK’s looming energy crisis. According to Peter, this was not a very cost effective approach, he stressed that there are other solutions out there,  however they are being ignored. He also went on to explain that aside from the problems introduced when building new plants, the older nuclear power plants are still causing waste issues, for example the Sellafield plants are currently polluting the local air with plutonium. To counteract this Gregg explained that it is a relatively new technology, and with all early stages in technologies there is going to be problems, the important thing is to develop a learning curve. This is where the UK are having issues, because there is no consistency and data logging of the nuclear industry progress, there are no learning curves and therefore problems tend to reoccur rather than get resolved. He also went on to reinforce the point I mentioned in the last article, that nuclear power can also be used to produce energy indirectly in producing biofuels. However Peter thinks biofuels are inefficient.  

We then went on to look at the issues faced within geological disposal of nuclear waste and whether it is wise to put into practice stakeholder engagement. Geological disposal simply means that the nuclear waste will be buried hundreds of meters below the ground in a stable geologic environment.  Stakeholder engagement allows any individual, community or organisation that may be affected by the waste disposal to have meaningful opportunities to express their views, which will be then be taken into consideration in the decision making process. Gregg fully supports this idea and believes that it promotes democracy, stating that consultation of the locals is very important. However Peter counteracted this stating that firstly people are presented with insufficient information in order to make their decisions, and somethings are being held back from them. He also explained that nuclear waste outlasts humans and therefore the people of today will be making a decision for future generations who will have to accept the decisions by default. Furthermore he also went to explain that science isn’t always right and therefore there could be some serious consequences for the locals’ health,and he finally added that the UK has proven to be geologically unsuitable for nuclear waste disposal. Gregg replied to this by stating that the stakeholders would regulate the scientific inaccuracies, and that rather than using the UK negotiations could be struck with other countries.

We discussed the impact government has on the nuclear industry. Greg explained that the government were in favour of nuclear power simply because it cuts CO2  emissions significantly. However Peter stated that this is because they are not educated properly on the technology and are blindly following it. He then went on to explain that allowing people holding bachelors of arts and business degrees to read, analyse and understand scientific reports in order to make decisions regarding nuclear energy isn’t exactly the most confidence inspiring method. This results in the government ignoring the uncertainties and doubt regarding low dose radiation  with regards to how dangerousit actually is. The government also fully support the reprocessing of nuclear waste streams to produce one spent fuel, which Peter explains only cuts 20% of the fuel and increases operating costs by 20% stressing that economically it is a very bad option. Gregg explains that reprocessing waste streams allows us to deal with one spent fuel rather than several different waste streams.

Finally we concluded on the topic of public perception and how information and science reports are tailored to favour nuclear energy introduction,  Peter explained. He states that there is no transparency in information and that the public should be able to access all information available in order to have faith and trust nuclear research. However Gregg responded to this by explaining that some information needs to be keep confidential for the safety of the country to avoid terrorist threats etc…

It can be seen from this brief summary of the debate that it is difficult to conclude whether or not to adapt nuclear energy within the UK. The positives of this technology have been looked into and the debate was inconclusive, so all that remains is to ask ‘What are the serious disadvantages to this technology that are pushing people such as Mr.Wilkinson to take such a strong stance against it?’