Features

Whether you turn out to be a good or bad mother is partly down to how you were treated by your own mother: at least if you are a rat.

Rats need their mothers to lick and groom them in the first week after they are born. If that doesn’t happen, it leads to poor outcomes in terms of how long the newborn rat can expect to live, its ability to cope with stressed conditions such as scarce food, and its ability to be a good mother themselves.

This is an example of a type of inheritance from one generation to the next that doesn’t lie simply in the genes and DNA sequences we receive from our parents. Instead, biological outcomes are decided by factors that affect which of our genes are active, rather than changes in the DNA itself.

This is called epigenetics: a research area that seeks to explain how genes are switched on and off, and how these controls are inherited, determined during development of the embryo, or affected by environmental factors.

‘Cancer is largely an epigenetic disease,’ says Professor Jane Mellor of the Department of Biochemistry. ‘The pattern of genes that are active in cancer cells can tell us a lot about how the cancer will progress. We find that tumour suppressor genes are often switched off and that tends to mean a poor prognosis for the patient.’

‘In agouti mice, the diet of the females can influence the coat colour of their pups through epigenetic changes,’ she adds. Agouti mice are named after their brown coats, which can vary from a pale yellow to a dark brown according to the level of one protein. ‘The diet of the mothers can also affect the birth weight, obesity, and disease susceptibility of the pups through changes acquired in the womb.’

There are two clear mechanisms that change which of our genes are active. One involves RNA. For example, women have two X chromosomes and one has to be switched off to avoid two copies of every gene on the X chromosome being used. This is done using an RNA molecule.

The other mechanism involves modifications to the chromosome itself. Chromosomes consist of a DNA molecule wrapped up around globular proteins called histones. The position of the histones on the DNA can change which genes are expressed, and there is a whole raft of chemical modifications that can be made to the histones that also determines which genes are active.‘

These different modifications are like little flags that show which genes are active and which are switched off,’ says Professor Mellor. ‘It’s a histone code that determines which gene products are made and when.’

‘This has led to the idea of an “epigenome” – much like the human genome – where we endeavour to map out all the modifications, where they are, in what tissues of the body, and at what time in development.’

‘The pattern differs over time and according to the environment we experience,’ she explains. ‘While there are potentially limitless modification patterns, we are learning some of the rules. We can predict from certain modifications as to whether that gene is active.’

Professor Mellor’s group works on yeast. ‘Yeast’s simplicity makes it a great system for understanding the basis of epigenetics,’ she says. ‘We’re able to look at the environmental signals that influence epigenetics and determine what it is that leads to chromosome modifications.’

For example, in everything from yeast to mammals, a starvation diet often allows you to live longer. Professor Mellor’s work has gained a handle on how this occurs. Under starvation conditions, or at least ‘calorific restriction’, she explains, ‘a different set of genes are brought into play to maintain metabolism and give enough energy to survive. This different set of active genes seems to allow yeast to live longer.’ 

Some galaxies, like some humans, can enter a period of graceful decline rather than suffer violent transformation, according to two new studies.

The findings, from the STAGES project and Galaxy Zoo, suggest that red spiral galaxies make up one fifth of all galaxies and represent a 'missing link' [see BBC Online] between 'young and vigorous' star-forming blue spiral galaxies and mostly 'old, dead and red' elliptical galaxies where star formation has shut down.

The studies were led by researchers from Oxford University and the University of Nottingham and are published online by the Royal Astronomical Society [read the results here and here].

Galaxy Zoo team leader Chris Lintott of Oxford's Department of Physics said: 'Everyone thought they knew that spiral galaxies were blue - but the public's results collected by Galaxy Zoo have shown that what every astronomer knew wasn't quite true;' [more in Universe Today]. 

Whilst Galaxy Zoo enlisted volunteers to help classify and detect the red spirals across a huge chunk of the sky, STAGES used the Hubble Space Telescope to take a detailed look at red galaxies in the A901/902 supercluster.

Oxford's Dr Christian Wolf, who helped lead the STAGES study, said: 'For the STAGES galaxies, the Spitzer Space Telescope provided us with additional images at infrared wavelengths. With them, we were able to go further and peer through the dust to find the missing piece of the puzzle.'

What the team found was that the red spirals in the supercluster were hiding low levels of star formation behind a veil of dust - activity that was only detectable in the infrared spectrum.

It suggests that if a galaxy is large enough and the local environment is relatively benign then a 'lively' blue spiral won't necessarily suffer a violent transformation into a 'dead' red elliptical: instead star formation is more gradually shut down leaving the delicate spiral arms of a galaxy intact - creating a red spiral.

Further work is needed to find out what exactly shuts down star formation in such a gentle fashion.

Road-building in Africa's Congo basin could spell catastrophe for the forest elephant.

New research by WCS and Save the Elephants published today in PLoS One shows that encroaching roads create a 'siege mentality' in forest elephants as they avoid roads, associating them with the threat of poaching.

A spurt of road-building in the area driven by increased logging and mining is dramatically decreasing the areas of roadless wilderness in which forest elephants feel safe to roam. Forest elephants have responded to the threat by dramatically shrinking their home ranges into ever-smaller 'virtual prisons' bounded by roads.

'There is a colossal threat to elephants from encroaching roads into the forest and to the entire diversity of life in that habitat' said co-author Iain Douglas-Hamilton, a Research Associate at Oxford's Department of Zoology. He questioned a recent decision by the IUCN to downlist the conservation status of the African elephant from vulnerable to near-threatened.

The researchers, led by Steve Blake of WCS, tracked 28 elephants fitted with GPS collars to discover how roads were affecting their movements. They found that all roads restricted elephant movements with just one collared elephant crossing a road outside a protected area, only doing so at 14 times normal speed.

The worry is that, with areas of roadless wilderness shrinking by up to 89 per cent, the 'imprisoned' elephants will miss out on access to vital food sources and could see them both become more aggressive and give birth to fewer offspring.

The underlying message from the research seems clear: save the wilderness or lose the forest elephant. 

Is it better to sterilise males with a dose of radiation or by inserting a gene?

That's part of the thrust of an article by Clive Cookson in the FT on the work of Oxford spinout Oxitec.

Of course what we are talking about are males of insect species that bring untold suffering to human populations around the globe.

The basic idea is simple: release large numbers of sterile males into infected areas so that they mate with all the available females who then produce no offspring.

But there's a problem: up until now the sterilisation has been achieved using radiation, but this doesn't work with the mosquitoes carrying dengue fever: unfortunately a dose high enough to render males sterile will kill or incapacitate them.

Now, in collaboration with Oxford scientists, Oxitec have found a more targeted way to sterilise male mosquitoes by inserting a 'dominant lethal' gene. 'The males produce viable sperm which will fertilise the egg, but the embryo [larva] dies in development,' said Oxitec's Luke Alphey, who left the University this year to work for the company full time.

So you get sterility AND virility.

It's an elegant solution which uses the antibiotic tetracycline to suppress the gene so that 'sterile' mosquitoes can be bred (remove tetracycline and any larva die). 

Of course many will baulk at the idea of unleashing a 'genetically modified flying army' into the wild. But, according to Luke, the gene can't 'escape' because the sterile males can't pass it on. 

The reaction of those in dengue-affected areas will be interesting. So far alternative approaches including insecticide fogging and improved sanitation haven't had much impact on the 100 million or so people afflicted by dengue every year.

If you lived under the threat of this disease would you be squeamish about releasing GM insects to destroy an insect species that is, in any case, alien to the region?

In a fascinating article in Scientific American Oxford's Gero Miesenbock explores the history of optogenetics - combining optics and genetic engineering to study specific types of cells.

Gero's particular interest is in combining genes that encode for cells that either emit or respond to light with neurons: in order to study brain circuitry.

He recently found a brain circuit in the olfactory system of fruit flies that produces noise - a discovery that has wider implications, as the basic architecture of a fruit fly's olfactory system is the same as a human's. Before that he had shown how stimulating the brains of fruit flies using a laser can cause female flies to perform a male courtship dance.

The Scientific American piece is well worth reading in full, but one particular point caught my eye when he goes on to discuss how the benefits of such research might one day impact on medicine:

'it would seem arbitrary and hypocritical to draw a sharp boundary between physical means for influencing brain function and chemical manipulations... In fact, physical interventions can arguably be targeted and dosed more precisely than drugs, thus reducing side effects.'

It's easy to fall prey to the understandable fear that physical interventions in our brains risk turning us into zombies or will-sapped cyborgs but are we all too easily overlooking the same risks associated with the drug cocktails patients routinely swallow?

I think we might look on such physical 'mind control' approaches differently if, in the future, they could offer relief from movement disorders such as Parkinson's, from debilitating behavioural disorders, and maybe eventually restore our lost senses.

As Gero comments, such direct approaches are still some way off. But right now optogenetics offers the promise of revealing new targets for drugs that could tackle anything from obesity to insomnia and anxiety.

Thanks to the work of Gero and others the 21st Century may genuinely turn out to be the 'Century of the Brain'.