Features

The elements of a new pathway likely to be involved in most body functions – from blood flow to metabolism and fertilisation of egg cells – have been identified by an international team in which researchers in the Department of Pharmacology took a leading role.

The discovery, reported in Nature, could provide new targets for drug development for diabetes, heart abnormalities, and many other conditions.

‘Calcium plays a vital role in the body,’ says Dr John Parrington. ‘And it’s not all about building healthy bones and teeth. Calcium is used to coordinate and control many different events, responses and reactions in the body.’

Bodily processes as diverse as heart contraction, nerve growth, control of appetite, regulation of the immune system, and insulin secretion by the pancreas are mediated by calcium. Each of these processes requires cells to have a coordinated, measured, and timed response. And cells use calcium to achieve this.

Calcium ions are released from stores within cells in response to signals from hormones or other chemicals in the blood, and the sudden increase in the amount of calcium present triggers the right physiological response – whether that’s contraction of a heart muscle cell or release of insulin by a cell in the pancreas. Of course, when this process gets disrupted, it can lead to a range of different conditions.

It’s in our basic understanding of how these chemical messages mediate important physiological events in the body at the molecular level, that Professor Antony Galione and John Parrington, along with researchers at the University of Edinburgh and colleagues in the US, have made a breakthrough.

The release of calcium from stores in the cell can be triggered by three different chemical signals or messengers. They are called IP3, cADPR and NAADP. The IP3 system is well known, and that involving cADPR is partially understood. What the Oxford team has done is reveal exactly how the chemical messenger NAADP has an effect. Previously this was entirely unknown.

The team identified a set of protein channels that sit in a compartment of the cell called the lysosome. (This is interesting in itself, as the lysosome was previously thought of pretty much as a dustbin in which unwanted substances were broken down.) They have shown that NAADP triggers the protein channels to release calcium held within the lysosome.

‘It's been a bit of a detective story. We knew that there was this chemical NAADP and we had proposed from our earlier studies that it released calcium from lysosomes. However, our discovery of a new class of calcium release channel opened by NAADP on the lysosome really has been the acid test,’ says Antony Galione, who is head of the Department of Pharmacology. ‘This opens an entirely new chapter in calcium signalling, which is important since most cellular activities are either directly or indirectly controlled by calcium.’

‘Now with the identity of the NAADP receptor uncovered, the possibility of designing new drugs to combat conditions such as diabetes, obesity and abnormalities of the heart and immune system, have been greatly advanced,’ adds John Parrington. They are already beginning to reveal the potential for human health, showing that the newly identified channel is critical.

‘”Knockout” mice, from which the gene for the protein channel has been deleted, show abnormal NAADP-induced calcium signals in the pancreatic cells that secrete insulin in response to blood sugar levels,’ explains John Parrington. ‘This finding could have great relevance for understanding conditions such as diabetes.’

The hope now is that drugs can be designed to target the protein channel in the appropriate way and restore its function where it is impaired.

How did you celebrate April 22 and its heroic alter ego Earth Day?

Our friends at the Said Business School organised a conference, Beyond Kyoto, focusing on green innovation and technology and how we can support entrepreneurship that solves the problems of the 21st Century.

Topics covered included climate change adaptation, clean energy, learning for sustainability and entrepreneurship in the Oxford area.

Amongst the speakers was Malcolm McCulloch from Oxford's Department of Engineering Science. Malcolm and his team are behind a range of exciting green innovations including a smart meter to help people manage their electricity use, research into novel refrigeration technology, not to mention working on the electrics for the stunning zero emission Lifecar.

If engineers can keep inventions like these coming then the future could be exciting as well as green. 

Today Oxford's Isobel Hook will be telling attendees at the JENAM astronomy meeting all about the European Extremely Large Telescope [E-ELT].

Sometimes scientists are guilty of hyperbole in the naming of instruments but in this case 'extremely' is entirely justified as, with a mirror 42m in diameter, the E-ELT would be four times bigger than the biggest optical telescopes in use today [the Southern African Large Telescope, for instance, has a 10m mirror].

Why is mirror size important? Because for optical astronomers the size of your mirror determines the sharpness of your image - roughly speaking a mirror four times the size gives four times the sharpness - making it possible to see much smaller objects.

This is especially important in the search for exoplanets, planetary bodies orbiting other stars. Massive instruments such as E-ELT would offer the first realistic chance of directly imaging 'normal' [ie non-massive, non-luminous] planets like the Earth.

The E-ELT would also enable us to do some very cool galactic navel-gazing, staring into the heart of our own Milky Way to see whether it harbours a supermassive black hole as part of an Active Galactic Nucleus [AGN].

Isobel Hook, of Oxford's Department of Physics, is leading the science case for E-ELT and tells me that the aim is to create a flexible instrument that could perform a wide variety of experiments.

The wide range of science such a telescope could do is a powerful incentive to overcome the many technical and logistical challenges in building a telescope quite this big.

In fact the E-ELT is only possible because of advances in the field of adaptive optics, making it possible to combine the light from hundreds of smaller mirrors into a single image (rather like an insect's compound eye).

Let's hope E-ELT is successful so we can see what we can see...

A six-year history of the diet and behaviour of four elephants in Kenya has been compiled by scientists analysing their tail hair.

As BBC Online report the team, which includes Iain Douglas-Hamilton, a Research Associate at Oxford's Department of Zoology and founder of the charity Save the Elephants, has shown that ratios of carbon isotopes found in tail hair correlate strongly with satellite measurements of the kind of vegetation available for elephants to eat at different times of year.

Coupled with GPS observations of elephant movements, this technique gives scientists the chance to see how they, and other animals, might be changing their foraging habits in response to changing climatic and environmental conditions.

In the future it could make it possible to reconstruct past climate events - such as droughts or flooding - through the eyes of a wandering pack of pachyderms. 

A report of the research is published in PNAS. 

Maybe it’s simple mammalian prejudice but most of us don’t stop to consider flies having sex, let alone having sperm.

But of course they do, and Oxford’s Stuart Wigby has found that a study of the chemicals male flies release along with their sperm could be important in tackling insect pests as well as giving us a fresh insight into sexual competition in many species, including our own.

A team led by Stuart report in Current Biology that when faced with sexual competitors male fruit flies transfer more chemicals to females in an attempt to change their sexual behaviour and physiology.

This sexual ‘chemical warfare’ between males revolves around seminal fluid proteins that are transferred in the fly’s seminal fluid alongside sperm. In insects these proteins can cause females to store sperm, lay eggs faster, and can act as anti-aphrodisiacs, making females less sexually receptive.

The team showed that male fruit flies [Drosophila melanogaster] use these proteins strategically; increasing the amount transferred when other males are present. They also found that males that are able to transfer more of these proteins have more offspring – making it likely that the amounts delivered determine the reproductive success of males.

Stuart told us: ‘As similar proteins are known in other species including arthropods and mammals – including humans – our results give a tantalising insight into how the different sexual strategies of males and females have evolved.’

‘Our findings could prove important for controlling the insect pests that damage crops or carry diseases. At the moment the sterile males used to control populations of pest insects are often not very successful at out-competing male rivals in the mating game; this research suggests how future control programs might selectively breed sexually competitive males.’

Dr Stuart Wigby is based at Oxford’s Department of Zoology