Biotech for all – taking science back to it’s roots?

This morning I came across a very interesting TED talk by Ellen Jorgensen entitled “Biohacking — you can do it, too” (http://on.ted.com/gaqM). The basic premise is to make biotech accessible to all, by setting up community labs, where anyone can learn to genetically engineer an organism, or sequence a genome. This might seem like a very risky venture from an ethical point of view, but actually she makes a good argument for the project being at least as ethically sound than your average lab. With the worldwide community of ‘biohackers’ having agreed not only to abide by all local laws and regulations, but drawing up its own code of ethics.

So what potential does this movement have as a whole? One thing it’s unlikely to lead to is bioterrorism, an idea that the media like to infer when they report on the project. The biohacker labs don’t have access to pathogens, and it’s very difficult to make a harmless microbe into a malicious one without access to at least the protein coding DNA of a pathogen. Unfortunately, the example she gives of what biohacking *has* done is rather frivolous, with a story of how a German man identified the dog that had been fouling in his street by DNA testing. However, she does give other examples of how the labs could be used, from discovering your ancestry to creating a yeast biosensor. This rings of another biotech project called iGem (igem.org), where teams of undergraduate students work over the summer to create some sort of functional biotech (sensors are a popular option) from a list of ‘biological parts’.

image

The Cambridge 2010 iGem team made a range of colours of bioluminescent (glowing!) E.coli as part of their project.

My view is that Jorgensen’s biohacker project might actually have some potential to do great things. Professional scientists in the present day do important work, but are often limited by bureaucracy and funding issues – making it very difficult to do science for the sake of science. Every grant proposal has to have a clear benefit for humanity, or in the private sector for the company’s wallet, which isn’t really how science works. The scientists of times gone by were often rich and curious people, who made discoveries by tinkering and questioning the world around them, and even if they did have a particular aim in mind they weren’t constricted to that by the agendas of companies and funding bodies. Biohacking seems to bring the best of both worlds, a space with safety regulations and a moral code that allows anyone to do science for whatever off-the-wall or seemingly inconsequential project that takes their fancy – taking science back to the age of freedom and curiosity.

Neuroscientists Make Declaration On Animal Consciousness

Scientists have officially acknowledged that birds have consciousness, and can experience emotions.

On 7/7/2012 a group of prominent neuroscientists signed a declaration supporting the view that non-human animals experience consciousness. The statement claims to be a ‘re-evaluation of previously held preconceptions’. It states that:

Convergent evidence indicates that non-human animals have the neuroanatomical, neurochemical and neurophysiologial substrates of conscious states, along with the capacity to exhibit intentional behaviours‘.

Unfortunately the declaration doesn’t define clearly what exactly the ‘consciousness’ they are referring to is. Instead the text switches between referring to different elements of conscious experience, such as arousal (e.g. levels of sleep and attentiveness), conscious decision making, perceptual distortions (e.g. hallucinations) and the experience of emotional states. As the concept of consciousness is a notoriously difficult one to define, the lack of an operational definition makes the declaration somewhat difficult to interpret.

A further peculiarity of the declaration is that it states something which I suspect the vast majority of scientists working in the fields of neuroscience, psychology and animal behaviour have believed for some time. Indeed I suspect a significant proportion of the ‘general public’ would accept that most animals have some level of conscious understanding, especially mammals. The declaration isn’t therefore heralding a breakthrough in scientific understanding, even if it does contradict certain religious and philosophical standpoints that propose consciousness as a uniquely human characteristic.

Despite these reservations, the declaration may prove to be of importance. It focuses on the commonalities between different animals in the neural structures supporting various conscious experiences, and discusses the implications this may have for understanding the development of consciousness through evolution. It represents an official acknowledgement that a larger range of animals experience consciousness that many may have previously believed, based off the proposition that absence of a cerebral cortex does not preclude conscious thought. Those animals considered ‘conscious’ can therefore include non-mammalian creatures such as insects and cephalopods. The declaration may hopefully lead to greater discussion of both the nature of consciousness, and the relationship between humans and other animals.  More importantly it may facilitate political changes to ensure the more humane treatment of animals.

A full text of the declaration can be found at http://fcmconference.org/img/CambridgeDeclarationOnConsciousness.pdf

Scientists discover bees that can reverse brain aging

By Maria Panagiotidi

Scientists at Arizona State University have discovered that older honey bees can reverse brain aging when they take on nest responsibilities typically handled by much younger bees.

This finding could provide alternative interventions for the treatment of age-related dementia. Current research focuses mainly on potential new drug treatments.

The study was published in the scientific journal Experimental Gerontology by a team of scientists from ASU and the Norwegian University of Life Sciences, led by Gro Amdam. The researchers found that tricking older, foraging bees into doing social tasks inside the nest causes changes in the molecular structure of their brains.

Previous research on honey bees has found that bees that stay in the nest and take care of larvae – the baby bees – remain mentally competent. However, after a period of nursing, bees fly out looking for food and begin aging very quickly. The effects of aging are visible after two weeks in the appearance of the foraging bees (worn wings, hairless bodies) and more importantly, in their brain function. Specifically, these bees lose the ability to learn new things.

Influenced by recent studies on brain plasticity, Amdam and colleagues wanted to see what would happen if the foraging bees returned to the nest and took care of the larval babies again.

The results of the experiment were fascinating. After 10 days, about 50 percent of the older bees caring for the nest and larvae had significantly improved their ability to learn new things.

The change observed in the older bees was not just behavioural but also physiological; Amdam and colleagues discovered a change in proteins in the bees’ brains. After comparing the brains of the bees that improved to those that did not, they found that two proteins had noticeably changed: Prx6 and “chaperone” protein. Both proteins have been previously found to protect the brain against diseases such as Alzheimer’s.

This finding could lead to the development of a drug that could help older people maintain brain function. However, many years of basic research and trials will be needed before such a drug becomes commercially available.

For now, Amdam and colleagues propose that social interventions might help our brains stay younger. Since the proteins being researched in people are the same as those found in bees, it is possible that these proteins may be able to respond to specific social experiences. Further research is needed on mammals in order to confirm that the same molecular changes occur on other species’ brains.

 

Reference

Nicholas Baker, Florian Wolschin, Gro V. Amdam. Age-related learning deficits can be reversible in honeybees Apis melliferaExperimental Gerontology, 2012; DOI: 10.1016/j.exger.2012.05.011

First Steps Toward Emergence of Life Theory

By Stephen Sadler

What turned a primordial mixture of amino acids and proteins into the first organized, self-replicating unit? What was it that breathed the vital breath into a collection of inanimate chemical building blocks, giving rise to an unbroken chain of evolution stretching three and a half billion years into the future and culminating in us?

For many years Kauffman has studied the mathematics behind groups of molecules known as ‘autocatalytic sets’. These sets of molecules and their associated chemical reactions are special because they form self-sustaining systems which, given a ‘food source’ of simple molecules, are able to form more complex molecules which themselves catalyse, or speed up, reactions which give rise to other molecules in the set. In this way, they form “functionally closed” structures (see Figure 1) that speed up the production of the members of the set, promoting the existence of the set as a whole.

Figure 1: an example of an autocatalytic set. Black dots represent molecules in the set, whilst white boxes represent reactions. Solid arrows stand for reaction inputs and outputs, and dashed arrows indicate catalysis. Because each arrow ends on a molecule in the group, the group is said to be “functionally closed”.

To see what all this has to do with life, we must define what we mean by “life”. Whilst definitions vary, most share some common themes, for example: self-organisation, self-replication, and the ability to evolve with successive generations. Kauffman himself has defined a living organism as “an autonomous agent or a multi-agent system capable of reproducing itself or themselves, and of completing at least one thermodynamic work cycle” [1].

So could autocatalytic sets fulfil these criteria? Almost by definition their existence promotes the proliferation of their constituents, which sounds remarkably like self-replication. Their closed structure and well-defined flow of reactants and catalysts through reactions also sounds like it might fulfil the self-organisation criterion. But can they evolve? It is this question that Kauffman’s latest work addresses.

The group studied the mathematical properties of autocatalytic sets and made the remarkable discovery that any given set can be decomposed into so-called ‘irreducible autocatalytic sets’. What’s more, the number of irreducible autocatalytic sets that any larger autocatalytic set can be decomposed into rises exponentially with the size of the larger set. Since these sets overlap to some degree, they can be said to be mutually dependent, and it is not too much of a leap of faith to imagine them beginning to behave as the elements of a ‘meta autocatalytic set’.

“In other words, self-sustaining, functionally closed structures can arise at a higher level (an autocatalytic set of autocatalytic sets), i.e., true emergence,” the group say.

The combining and splitting of these functionally-closed, self-replicating entities can, according to the group’s paper, give rise to inheritance, mutation and competition. In other words: evolvability.

However, the authors don’t stop there. Is it too far fetched, they ask, to “consider a complete cell as an (emergent) autocatalytic set?” And if not, then why not think “of the collection of bacterial species in your gut (several hundreds of them) as one big autocatalytic set”? Going one step further, could the theory not be applied to ecology to describe any mutually dependent set of organisms, they ask? Could the economy not be viewed as an autocatalytic set, with its processes (reactions) assembling complex structures out of more simple ones (reactants), facilitated by tools, factory production lines and humans (catalysts)?

These are big ideas and, by the authors’ own admission, rather speculative, but with the tantalising possibility of a single theory to explain the phenomena of emergence, functional organisation and the origin of life, it seems difficult to disagree with them when they conclude: “we believe that these ideas are worth pursuing and developing further”.

A preprint version of the group’s paper can be found at http://arxiv.org/abs/1205.0584

[1] 2004, “Autonomous Agents”, in John D. Barrow, P.C.W. Davies, and C.L. Harper Jr., eds., Science and Ultimate Reality: Quantum Theory, Cosmology, and Complexity, Cambridge University Press.

 

Scientists Implant Biofuel Cell in Living Snail

By Maria Panagiotidi

Researchers led by Evgeny Katz, the Milton Kerker Chaired Professor of Colloid Science at Clarkson University, have implanted a biofuel cell in a living snail. Their findings were published in the Journal of The American Chemical Society.

Researchers led by Evgeny Katz, the Milton Kerker Chaired Professor of Colloid Science at Clarkson University, have implanted a biofuel cell in a living snail. This is the first incidence of an implanted biofuel cell continuously operating in a snail and producing electrical power over a long period of time using the snail’s physiologically produced glucose as a fuel. (Credit: Image courtesy of Clarkson University)

The “implanted battery” can generate electrical power for several months driven by glucose, which is produced by the snail.

This is the first reported incident of an implanted biofuel cell operating in a snail and producing electrical power over a long period of time using as fuel the glucose that is physiologically generated by its host.

Implantable biofuel cells have been suggested as sustainable micropower sources operating in living organisms, but such systems are still very challenging to design. In the future, implanted fuel cells that are driven by glucose generated by their host could power medical devices in humans or environmental sensors in animals.

Evgeny Katz and his colleagues made the electrodes of their fuel cell out of densely packed carbon nanotubes, and attached glucose-oxidizing and oxygen-reducing enzymes to them. The authors then implanted the electrodes into a snail (Neohelix albolabris). After decreasing the rate of current extraction to match the snail’s slow glucose transport and metabolism, they got continuous electrical output for an hour. The amount of electricity produced was far below that of just one AAA battery, but the group of scientists aim to increase it in future experiments. The fuel cell remained functional in the snail for several months during which the animal was allowed to roam freely and live an almost normal life.

The aim of this research is creating insect cyborgs, an idea that has been funded by the U.S. Department of Defense.

 

Reference

Lenka Halámková, Jan Halámek, Vera Bocharova, Alon Szczupak, Lital Alfonta, Evgeny Katz. Implanted Biofuel Cell Operating in a Living SnailJournal of the American Chemical Society, 2012; : 120308155036002 DOI:10.1021/ja211714w

You can find the article here:  http://pubs.acs.org/doi/abs/10.1021/ja211714w 

 

 

Cholesterol treatment used in treatment of hepatitis C?

By Kathryn Higgins

A molecule that is known to take up cholesterol into a cell has recently been identified to allow entry of the hepatitis C virus (HCV) into liver cells. This may lead the way for new therapies to be developed.

Hepatitis C is a disease that primarily affects the liver. It is caused by HCV, which is spread by blood-to-blood contact. Once infected, HCV can persist in the liver causing scarring and ultimately leading to liver failure or cancer. The World Health Organisation (WHO) estimates that three per cent of the world’s population (about 170 million) have hepatitis C, and although treatment is available, more effective therapies are needed. Liver transplantation is one such treatment, but infected patients find the virus attacks the new liver.

Previous studies have shown the involvement of cholesterol in HCV infection, thus it was hypothesised by researchers at the University of Illinois at Chicago that a cell surface molecule (a receptor) called Niemann-Pick C1-like 1 (NPC1L1), which is known to facilitate the uptake of cholesterol into the cell, may also be involved in trafficking the virus into the cell.

The research team headed by Susan Uprichard, assistant professor of Medicine, Microbiology and Immunology, conducted experiments to determine the role of NPC1L1 on viral uptake. Experiments involved blocking the receptor and reducing expression by using knock-out models. The results demonstrated that blockade or knock-out of NPC1L1 impaired liver cell infection with HCV.

To confirm these studies further, an inhibitor of NPC1L1 called ezetimibe, which is clinically used to lower cholesterol levels, was also tested. Results validate previous findings showing blockade of HCV uptake into the cells and preventing infection.

Current drugs used to treat hepatitis C are known to be toxic, and cannot be used by transplant patients, therefore ezetimibe may provide a solution as a new anti-hepatitis agent. Therapy with ezetimibe alone or in combination with current drugs may improve patient treatment by targeting the receptor NPC1L1 and preventing HCV entry into liver cells.

Reference:
Sainz et al, (2012) Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nature Medicine. Ahead of print.

The paper can be found at: http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm.2581.pdf

Transparent tissues offer a window into the brain

By Kathryn Higgins

 

A revolutionary reagent has been developed that can literally turn biological tissues transparent. Researchers from the RIKEN Brain Science Institute in Japan have developed a reagent which allows 3D imaging of the neuronal network deep inside a mouse brain.

Imaging and labelling of cell populations deep within tissue has been a challenge for scientists for many years. Although advances have been made in cell imaging there are still many obstacles to overcome. Tissues often have to be sliced 1mm thick for viewing under a microscope to dissect networks since imaging within deep tissues leads to many problems due to the lack of transparency of the tissue. Several clearing solutions have been developed but these have disadvantages such as expense and quenching of fluorescently labelled proteins that are often used in cell research to visualise the structures.

A research team led by Atsushi Miyawaki, however, have recently developed a reagent, after a chance observation, which may revolutionise deep tissue imaging by obtaining 3D images that are valuable for improving our understanding of biological organisms and how they function.

The reagent, called ScaleA2, is a highly effective clearing reagent, greatly improving the transparency of tissues, and stabilising fluorescently labelled proteins. This allows imaging to be done at a much greater depth than currently possible, providing detailed 3D visualisation of neuronal networks within the brain than has ever been managed before.

Current research using ScaleA2 was done using dead embryo tissue for imaging neurones and blood vessels deep inside the mouse brain. Miyawaki and his research team, however, believe that the scope for using ScaleA2 in other tissues and organisms is not limited, and are currently trying to optimise the reagent for use in live tissue. This would open the door to experiments that have never before been possible.

 

Image shows two murine embryos. The left embryo was placed in PBS, whilst the embryo on the right was incubated for 2 weeks in ScaleA2 solution.

 

 

Reference:

Hama et al, (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nature Neuroscience. Ahead of print.

The paper can be found at:

http://www.nature.com/neuro/journal/vaop/ncurrent/pdf/nn.2928.pdf

Credit card diagnoses HIV & Syphilis

Written by Iain Stewart

An article published in Nature Medicine, 4th August 2011, has shown scientists from Columbia University, New York, have created a new tool for efficient and reliable diagnosis of both HIV and syphilis.

Samuel Sia and his team of researchers have adapted the ‘ELISA’ technique into a portable and cheap procedure that can be used in remote parts of the world, giving results in under twenty minutes. ELISA (or enzyme-linked immunosorbent assay) is a well-known method, routinely used in laboratories, to detect the presence of antigens using antibodies.

Antigens are molecules, which when present in the blood, trigger an immune response from the body. Every cell in our body carries its own antigens, which are recognized as ‘self’, but foreign antigens from bacteria, viruses, and cells that are not our own, stimulate new antibody production.

Sia and colleagues scaled down the recognition of antigens into a plastic tool they term ‘mChip’ (microfluidic chip). All that is required is a microlitre of blood, taken directly from a pinprick, which is then passed through extremely narrow channels in a credit card sized device. The disease antigens are present where the channels form tight loops. When blood from an individual who has the virus flows through these loops, specific antibodies from the blood bind. Next, antibodies attached to silver particles are washed through and bind to the antibodies present, with the result of solid silver loop indicating the patient is positive for the specific disease.

This new tool displays many advantages over the current diagnostic strategies. It is low cost, as the mChip and reagents cost pennies to make. It can diagnose both HIV and syphilis in the same test, taking under twenty minutes compared to previous hours, days and even weeks. Its portable design allows it to be operated at the point-of-care, making it accessible anywhere in the developing world. A microlitre of whole blood is all that is necessary from the patient, while its ease of use requires minimal training for the operator. The result can be read without hi-tech optical equipment, is not open to interpretation, and has been shown to be as reliable as current techniques.

Exposing unborn children to the sexually transmitted disease, syphilis, leads to miscarriages, stillbirths and death of newborns. Fast diagnosis of pregnant mothers, and therefore treatment of syphilis with a single dose of penicillin, can significantly increase the survival of the unborn infant by preventing disease transmission through the placenta. Sia and colleagues’ data suggest 5000 syphilis-related deaths could be avoided in Rwanda alone, whilst the World Health Organisation estimates that the disease is responsible for 500,000 perinatal deaths in sub-Saharan Africa every year. 

As well as the obvious impact this technique could have on diagnosing HIV and syphilis at the point-of-care, this test can be used for pre-screening blood donations, and could eventually be used to diagnose a range of infectious diseases in poorly equipped areas all over the world.

Chin, C. et al. Microfluidics-based diagnostics of infectious diseases in the developing world. Nature Medicine. 4th Aug 2011, doi:10.1038/nm.2408

http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm.2408.html

http://www.who.int/reproductivehealth/topics/rtis/syphilis/en/index.html


credit card sized device.

doi:10.1038/nm.2408

channel loops, scale bar 1mm.

doi:10.1038/nm.2408  

A woman bathes an infant in rural Manara, Tanzania. Taken from www.who.int.

Blood Groups Could Become a Thing of the Past

 

Written by Matt Farley

 

New research from McGill University in Canada could do away with the need to classify blood by ‘type’, following a new technique to prevent mismatched blood from being rejected after a transfusion.

Along with the well-known A, B and O blood groups, there are a further 26 different blood types which have to be matched carefully when carrying out a blood transfusion – a mismatch can lead to the donated blood being rejected by the body which can be fatal. The ideal situation is for a ‘universal’ blood type which would be compatible with any recipient blood type.

Rejection occurs when the antigens on the surface of the donor red blood cells are of a different type to those on the recipient’s cells – previous attempts at avoiding this have focused on either removing the surface antigens from the donated blood using enzymes, or producing the blood outside the body from stem cells. These techniques have shown some success, but are hindered by their expense and complexity. The latest method, presented by Dr. Maryam Tabrizian and colleagues, instead aims to cover up the antigens and hide them from the host immune system – known as ‘immunocamouflage’.

Red blood cells from a selection of volunteers were coated in a layer of polyelectrolytes – small repeating units which self-assemble on the cell surface. Previous attempts at coating cells in this way using yeast and E.coli had shown promise, but it remained to be seen whether the delicate red blood cells would be able to withstand the process.

After coating, the cells were exposed to their opposite antibody and observed for any agglutination, or clumping of cells, that occurred. The coated cells were shown to remain free after addition of the antibody, suggesting that the antibodies had failed to recognise and bind the cell surface antigens. This was in contrast to the uncoated cells, which clumped together in the manner normally seen when mismatched blood samples are mixed.

Perhaps most importantly, the red blood cells showed no significant reduction in their ability to take up oxygen, implying that they would still be able to carry out their function within the body. The cells were also seen to produce ATP, an energy carrier – a good sign that metabolism was also functioning as normal.

It remains to be seen whether the technique will be as effective when tested in a living organism, but the results obtained so far appear promising. If effective, future blood transfusions could become a lot easier, and a lot less dangerous.

The paper accompanying this article is available online:

http://pubs.acs.org/stoken/presspac/presspac/full/10.1021/bm101200c

Red blood cells

Losing DNA made us human

 

Written by Olivia O’Sullivan

 

A study has shown that it may be DNA we have lost which sets humans apart from our nearest primate relatives. 

The majority of mutations in DNA are harmful, and a loss of genetic information might be assumed to be catastrophic. In a paper published last week in Nature, a team of researchers from Stanford University in California have challenged this by identifying the loss of particular regions of non-coding DNA to be a key factor in shaping our unique minds and bodies, thus setting us apart from chimpanzees and the rest of the animal kingdom.

By conducting a genetic comparison of the human genome with that of a chimp and a macaque the team found 510 DNA sequences missing in humans that were present in chimps, almost all of these sequences were from the non-coding region of DNA, i.e. chunks of DNA responsible for turning genes on or off . Two regions of particular interest were the androgen receptor (AR) gene and ‘GADD45G’ – a tumour suppressor gene involved in brain development.

The AR gene is implicated in the production of hard, keratinized penile spines which are found in many mammals and play different roles in different species. It is thought that penile spines may have been used as a way of competing with other males for mating partners by removing the sperm of competitors. It is believed that the molecular changes resulting in a loss of human penile spines has allowed us as a species to form more complex social structures by adopting monogamous reproductive relationships.

Another ‘lost section of DNA’ in humans was found to code for a tumour suppressor gene that normally acts to suppress brain growth, putting an evolutionary brake on the growth of specific brain structures zones in our primate relatives. This ultimately paved the way for the evolution of a larger human brain, giving us an intellectual edge over our fellow animals.

The results of this study certainly underlines the fact that genetic information is both gained and lost during evolution and that despite sharing approximately 96% of our DNA with chimpanzees, it is thought that this genetic divergence may have occurred more than 800,000 years ago when our ancestors split from the Neanderthal lineage. This is an exciting finding, opening up new areas for discovery through the analysis of the remaining 508 DNA sequences which promise to reveal further secrets about the molecular basis of human individuality.

 

References:

McLean, C. Y. et al. Nature 471, 216-219 (2011)