Features

It's no secret that OxSciBlog likes elephants but how do they feel about us and each other?

BBC 1's The Secret Life of Elephants [starts 14 Jan, 9 pm] intends to answer this question by giving us the gamut of elephant emotion from love and lust, through jealousy, fear and anger to grief.

The show follows elephants at the Samburu reserve in Northern Kenya and one of the featured researchers is Iain Douglas-Hamilton, a Research Associate at Oxford's Department of Zoology, founder of the charity Save the Elephants (STE).

A scan of STE's helpful blurb reveals that the three-part series will highlight some of the most interesting findings from the Samburu researchers over the past couple of years, including pachyderm compassion and grief, and how human influence is relegating elephants to smaller and smaller safe areas they find it stressful to navigate between.

I enjoyed what I caught of BBC 2's Elephants of Samburu last year [presented by Iain's daughter Saba] so I'm looking forward to a return with more emphasis on the science and conservation of these magnificent beasts.

Professor Helen Mardon is codirector of the Oxford Stem Cell Institute, part of the James Martin 21st Century School at the University of Oxford. I asked her about the potential for stem cell research:

OxSciBlog: What are stem cells and how could they be used in medicine?
Helen Mardon: Stem cells are cells from embryos, umbilical cord blood, or various sites in the adult such as bone marrow that can multiply and also have the capacity to form a range of different cell types in the body – to ‘differentiate’.

The capacity for such differentiation depends on the origin of the stem cells. Stem cells from the embryo have the ability to differentiate into all the different cell types that make up tissues such as cardiac muscle, pancreatic tissue, brain tissue and so on. Stem cells from adult sources, such as the bone marrow, have a more limited capacity.

Stem cell technology thus offers remarkable scope for the development of new cell-based treatments for a diverse range of diseases by allowing tissues in the body to be repaired or regenerated. This could include therapies for heart disease, neurodegenerative diseases such as Alzheimer’s and Parkinson's disease, diabetes, and tissue damage caused by injury.

OSB: What are the main challenges in making stem cell therapies a reality?
HM: There are several major challenges in developing successful stem cell-based therapeutics. For example, stem cells derived from human embryos currently need compounds derived from animal sources to grow, and this needs to be avoided if the cells are to be transplanted into humans. We need to understand exactly how to get stem cells to differentiate or turn into the particular type of cell for a desired type of tissue in the body, whether skin, heart muscle, or pancreatic tissue. Once transplanted into a patient, we want the stem cells to stay where we want them, and not disperse.

Finally, the risk of rejection of the cells by the body's immune system has to be overcome, as is the case for any tissue transplants. This can be done either by generating huge numbers of different stem cell lines to have the best chance of finding a good tissue match, or by manipulating the cells so that the immune system is not triggered.

OSB: How will the work of the new Oxford Stem Cell Institute approach these challenges?
HM: The Oxford Stem Cell Institute has brought together scientists from across the University who are leading world experts in different aspects of stem cell research. Between us, we are addressing these challenges in bringing stem cell therapies to the clinic. The Institute has enabled Oxford scientists with their different backgrounds to collaborate and facilitate a combined effort to take stem cell technology forward.

OSB: How should scientists, governments, and the public respond to ethical dilemmas about the use of stem cells?
HM: There should be open debate and discussion between scientists, governments and the public. It is critical that scientists are transparent about their research and are provided with a forum for conveying their discoveries and the possible implications to the public. Widening of public understanding of stem cell science is essential: an informed public is better placed to make reasoned judgements about ethical dilemmas.

OSB: What landmarks should we expect for stem cell science and medicine in the 21st century?
HM: We should be cautiously optimistic. We should expect to see major advances in stem cell science and its application in medicine as the technology improves. The bringing together of stem cell scientists from different backgrounds, together with continued significant funding opportunities, should drive the science forward toward the use of stem cells in the clinic. We are already seeing adult stem cells being used therapeutically and now it should be possible to begin to exploit the potential of embryonic stem cells.

Highlights from Oxford science in the news over Christmas:

Could that Christmas chocolate and wine have done you some good?

As newspapers including the Telegraph, The Sun and The Daily Mail reported, Oxford research focusing on the elderly suggests it just might.

Oxford and Norwegian researchers found that small amounts of chocolate, wine and tea can significantly boost the cognitive performance of the over-70s.

Flavonoids, micronutrients found in all three foodstuffs, may be behind the effect (although the researchers say other factors specific to these foods can't yet be ruled out).

Let in the lynx
Would reintroducing the lynx to Britain be the best way to control deer populations?

In the run up to the publication of the State of Britain's Mammals report David Macdonald of Oxford's WildCRU told The Independent lynx would provide a natural way of controlling deer numbers.

David comments that we shouldn't worry about sharing our landscape with these wild cats: 'There is enough food – there are all these roe deer that people are having to control and the lynx could help out... As far as I'm aware, there is no recorded case of lynx being any danger to people.'

Txt ur mood 
A system that enables clinicians to monitor a patient's moods by text message can help in the treatment of mental illness.

Developed by Oxford's Department of Psychiatry, with Oxfordshire and Buckinghamshire Mental Health, the system contacts patients every day and asks them to text back a letter code that corresponds to their mood.

As BBC Online report this simple approach enables clinicians to plot a patient's mood swings, monitor the effect of medication and identify when a face-to-face appointment or further assessment is needed.

Oxford's John Geddes said: 'When I see the patient in clinic I pretty much know how they have been... Basically, with this system we would hit the ground running and we can focus on trying to help them and their treatment.'

Nano-walker 
A new kind of 'walking' molecular machine might one day shift cargo around 'nano-factories' according to New Scientist.

They report on work by Oxford's Andrew Turberfield and colleagues into a 'nanobot' with DNA feet which 'walks' along a DNA track. Clever design ensures the Oxford nanobot doesn't detach itself from or destroy the track as it moves - there's no backtracking either as it can only move forward.

Andrew comments: 'At the moment, the nanobot has taken a single step but our ambition is to make it move 100 nanometres or more... We can already stop and start our motor by controlling the amount of fuel we add, but we could add other control signals to make walkers interact with each other, and could easily attach a cargo to the region that links the two legs.'

Species showdown
Finally, what animal could humans not live without?

During a debate at the Earthwatch Institute broadcast on BBC Radio 4 five scientists slugged it out to decide which species was irreplaceable.

After being put to an audience vote George McGavin of the Oxford University Museum of Natural History won the day with his persuasive argument in favour of bees.

A helping of seasonal science in which Oxford's Joseph Tobias exposes the scandalous life of the robin:

OxSciBlog: What, in evolutionary terms, explains the robin's aggressive territorial behaviour?
Joseph Tobias: Robins are a classic example of a species which survives by defending resources. They feed largely on ground-dwelling invertebrates, a food supply that can quickly be exhausted if too many individuals forage over the same patch of ground.

To maintain their food supply, they defend it aggressively against all-comers, much as we might get a little stroppy if someone was pilfering our fridge. Only in robins the stakes are higher because a cold snap and an impoverished food supply means death, and you can't get more non-adaptive than that.

OSB: What benefit/use is its distinctive red breast?
JT: The red breast appears to be an honest signal of competitive ability. It is fluffed out in displays between rival males, and between courting pairs. It contains information about the genetic quality of the individual, and so functions as a signal mediating conflict and courtship.

As with many such signals in the natural world, the display of honest signals can settle contests one way or the other without the need for direct aggression. This can save a lot of time, energy and injury. When resource value is high and robins equally matched, neither individual backs down and they will famously fight to the death.

OSB: Do we know what impact global warming is having on robin populations?
JT: No. The picture is highly complex. British robins will probably be in favour of global warming as many of them die during harsh winter weather. Spanish robins will probably be a little less enthusiastic as their summers may get too hot and dry.

In most winters a fair proportion of British robins migrate to France or even Spain, while a good number of Scandinavian immigrants swell the ranks of British residents. Warming may therefore lead to shifting patterns of migration, and a contraction of the southern boundary of the species' range.

OSB: How does food availability affect relations between male and female robins?
JT: Pairs of robins form very early, in January, if the food supply is sufficient for two individuals to share a territory. From January onward the female is silent and the male takes charge of territory defence; in April she builds the nest alone, and the pair collaborates to incubate the clutch and feed the offspring; in August the adults moult, the pair bond breaks down and the male and female go their separate ways. So far, the species is typical of many birds, except for the early pairing date.

However, from September onwards, the female experiences a large influx of testosterone, and she changes character. She breaks into song, and she competes aggressively with males for a winter territory. In effect, for a few short months, females become males and both sexes compete on an equal footing for space and resources. This period of the year perhaps explains why both sexes show the red breast. It also makes the robin a remarkable creature, with a highly unusual approach to territoriality. In no other British passerine do females sing, or defend their own territories. And very few British birds are so strongly territorial during the winter.

From January onward, female robins join forces with a male, and it is the timing of this switch-over that is governed by food supply. In high quality territories with plenty of food this can happen shortly after Christmas, but where food is scarce it is not possible for two birds to forage over the same space until February or March. Every year, 20% of male robins advertise their territories in vain, and fail to find a mate. Consequently, this places a high premium on defending the best possible patch to maximize chances of attracting a female early in the New Year.

OSB: Any other tidbits about how robins survive the British winter?
JT: For a species so intimately linked in our minds with cockiness and aggression, one of their most surprising habits is communal winter roosting. Up to twenty individuals, who have fought fiercely all day over the boundaries of their territories, will gather at dusk in a dense shrub to sleep. This behaviour is very rarely observed, as robins gather at their winter roosting sites at dusk. While it is not fully understood why they do this, they presumably gain some anti-predator or thermoregulatory benefit by abandoning their daytime disputes and roosting communally.

OSB: Where do your current research interests take you?
JT: My early forays into robin biology, involving bracing winter fieldwork in Cambridge Botanic Gardens, led to a fascination with the tropics, where things just seemed a whole lot warmer. I've been working there ever since, tackling a range of questions in evolutionary biology and conservation biology. Perhaps the biggest and most challenging of these is Darwin's "mystery of mysteries" - what processes cause species to multiply and to assemble into communities.

This puzzle takes me to the richest rainforests of Peru, where up to 500 bird species sometimes occur in a square km. Here, with studies of song, behavioural interactions and phylogenetics, I am finding out some fascinating things about how signals mediate their co-existence, and in turn how co-existence has influenced the evolution of signals. With a bit of luck and a lot of comparative genetics, I also hope to discover the key to that old chestnut: how they all got there in the first place. 

Dr Joseph Tobias is a postdoctoral researcher at Oxford's Department of Zoology.

‘Epigenetics is a blossoming area of science,’ says Dr Chas Bountra, chief scientist at the Structural Genomics Consortium (SGC) in Oxford. ‘We believe it will deliver new drugs for many common diseases, such as diabetes, cancer, and inflammatory diseases.’

The study of epigenetics tries to understand changes in the action of genes that are inherited but occur without any changes in the DNA sequences.

By understanding these mechanisms of genetic control at a level above the DNA code, researchers believe they can identify factors that lead to many diseases where this control goes awry.

Dr Bountra and the SGC are heavily involved in a new public-private partnership to systematically set about investigating the most important proteins involved in epigenetic control and kick-start the drug-discovery process. They, along with the Departments of Chemistry and Biochemistry, a government laboratory in the USA and pharmaceutical giant GlaxoSmithKline plc (GSK), have just received a £4.1 million investment from the Wellcome Trust over four years.

The funding will allow the partnership to generate chemical compounds or ‘probes’ that bind to 25 different epigenetic control proteins and stop them working. This allows the role of each protein to be understood and whether blocking the target could have a benefit in treating disease. Some of the chemical probes could turn out to be starting points for drug development.

‘To dissect the disease processes in the body, we need good tools, and chemical probes are some of the best,’ explains Dr Bountra.

The chemical probes will be made freely available to anyone in academia, biotech, or pharma. ‘We will provide a complete set of information along with samples of the probes – the three-dimensional structure of the protein target and the probe bound to the target, how to make the probe, and the pharmacological/biochemical activity of the probe – so that everyone has everything they might need to take this work forwards.’

This is a highly unusual step, says Dr Bountra. ‘Intellectual property in pharma has always been closely guarded and knowledge is not shared with other people. Here, GSK is contributing their compounds knowing the results will be made public. This is a major shift in the way pharma works with academia.’

The grant from the Wellcome Trust will be used to recruit 16.5 new employees in Oxford: 10.5 in the Structural Genomics Consortium, five in Chemistry and one in Biochemistry. The SGC will generate the target proteins, determine the structure of the proteins and the bound chemical probes, and all three Oxford groups will be involved in measuring the pharmacological activities of the probes.

The National Institutes of Health Chemical Genomics Center (NCGC) in Bethesda, USA, will screen their set of 270,000 compounds to see if any bind to each of the protein targets, absorbing all the cost themselves (which can be around £0.5 million for each screen: the agreement covers 20 high throughput screens), while GSK will be committing eight chemists at their sites in producing the chemical probes.

‘This will make a big impact in this area of science and drug discovery,’ says Dr Bountra. ‘I feel we will have been successful if we facilitate drug discovery in the area of epigenetics – if biotech and pharma take up these probes and start moving them into the clinic. On the way we will no doubt produce some first rate publications in collaboration with world leaders in epigenetics and drug discovery.’