Features

A new way of detecting TB inside cells has been developed by scientists from Oxford University and NIH in the US.

Methods for diagnosing TB haven’t changed much in a century, still relying on the staining of tissue sections and chest X-rays.

In a recent issue of Nature Chemical Biology Ben Davis, from Oxford University’s Department of Chemistry, and colleagues describe a new method which can, for the first time, detect TB inside cells using a small molecule.

‘We designed and created a fluorescent sugar that we discovered is a substrate for an enzyme, Ag85, found on the surface of TB bacteria,’ Ben told us.

‘The sugar is a variant of one that TB uses but is not used at all in mammalian biology. The Ag85 enzyme takes this and attaches a greasy lipid tail - this greasy product then becomes buried on the greasy surface of TB. The result is that the cell surface of the bug is fluorescently 'painted'.’

Ben explains that the net result is a selective labelling of TB even when the bugs are found inside mammalian macrophages, where it normally lies dormant in infected hosts. Other bugs are not labelled and other sugars do not work, so it's very selective.

He adds: ‘We've been able to use this here to map out aspects of TB cell biology but the implications for diagnosing and monitoring TB as a disease are clearly much broader.’

Professor Ben Davis is based at Oxford University's Department of Chemistry.

New radar imagery from the Alos satellite is helping researchers to map the devastating earthquake which hit Christchurch, New Zealand, on 22 February.

The Comet team, supported by the Natural Environment Research Council [NERC], are using Alos radar data to build up a picture of how the earth deformed during the quake in a synthetic aperture radar inteferogram.

'It's like a contour map but it's showing to the south-east of Christchurch that the ground motion is towards Alos. That's uplift,' Comet member John Elliott, from Oxford University's Department of Earth Sciences, told Jonathan Amos at BBC News Online.

'And then right under Christchurch, we see subsidence. That's partly due to liquefaction but it's mainly due to the way the Earth deforms when you snap it like an elastic band.'

During earth tremors the loose sediment on which Christchurch is built acts like a liquid and amplifies any shaking. Faults in the area are 'blind', that is invisible from the surface, meaning potential dangers are hard to spot or plan for.

John added: 'People knew they could get earthquakes further into the mountains; that's how they've been built in some ways, through earthquakes and all the faulting... But to get an earthquake right under their city will have been a surprise to nearly every single person.'

The team are hoping more data will help them to link the most recent shock with the larger quake which occurred in September last year.

Dr John Elliott is based at Oxford University's Department of Earth Sciences.

One of the key theories underpinning modern physics is being tested by the latest results from the LHC’s ATLAS experiment.

Supersymmetry theory says that every particle must have a Supersymmetric partner particle yet so far ATLAS hasn’t found a single one of these ‘sparticles’.

I asked Alan Barr, one of the Oxford University physicists behind ATLAS, about these new results and whether the theorists should be worried…

OxSciBlog: What is 'Supersymmetry' and why is it important?
Alan Barr: The subatomic world is described by a theory known as the ‘Standard Model’, which seeks to explain the basic building blocks of the universe, and the forces by which they interact.

The Standard Model has been very well tested over the last several decades, but it's known to have several nasty problems: for example it does not explain the origin of the gravitational force, nor does can it account for the invisible ‘dark matter’ that seems to make up the bulk of the universe. 

The theory of ‘Supersymmetry’ extends the Standard Model, and solves many of its problems. The clearest prediction of this grander theory is that for every known type of particle there should be a Supersymmetric partner particle, known as a ‘sparticle’.  

OSB: How is ATLAS helping in the search for ‘sparticles’?
AB: We can hunt for sparticles by studying the debris from the collisions at CERN's Large Hadron Collider. Einstein's famous formula E=mc² tells us that energy can be turned into mass, so provided that the collision energies are high enough - and that the new particles are light enough - then we expect that some fraction collisions will produce sparticles. The heavy sparticles will rapidly decay, but they should leave tell-tale signs in the ATLAS detector.
 
OSB: What do these latest results from ATLAS tell us?
AB: Our team has looked for the signs of particular sparticles - the so-called ‘squarks’ and ‘gluinos’ - from the data recorded by ATLAS last year. Our results show is that if these sparticles do exist, they must be heavier than previously thought. They must weigh more than about 800 protons - otherwise we would have seen them already. 

OSB: What more needs to be done to find out if Supersymmetry is real?
AB: There's certainly lots more work to do. We'll soon be firing up the accelerator again, and also increasing the rate of collisions. Then in 2013 we'll start running at even higher energies, which should give us sensitivity to even higher mass sparticles. 

OSB: What would it mean if we could prove/disprove Supersymmetry?
AB: If we can prove the theory to be correct then we can hope to learn about the 'missing' 96% of the universe - the part which is not made out of atoms. Quite apart from the cosmological implications this would be a most impressive experimental confirmation of a very elegant theory of nature.

If none of these sparticles can be found, even in the highest-energy collisions, then it's back to the drawing board for the theorists...

Dr Alan Barr is based at Oxford University’s Department of Physics.

In Alzheimer's disease, two proteins are known to accumulate and build up in the brain. One protein called amyloid β aggregates into large disruptive ‘plaques’, while tau protein forms tangled fibres within nerve cells.

Research has tended to focus on amyloid β, since small numbers of these proteins bound together are known to be toxic to the neurons in the brain.

But there is some evidence to suggest tau protein may also be involved in the processes which eventually lead to the memory problems and cognitive decline seen in Alzheimer’s.

Researchers at Oxford University have used a sensitive laboratory model of learning and memory to investigate any connection between amyloid β and tau. They found that tau is absolutely required for amyloid β to disrupt the function of the mouse nerve cells in the lab model. The results were published last month in the Journal of Neuroscience.

‘This is one of the first investigations of the mechanisms linking amyloid β and tau that is relevant to the early stages of Alzheimer’s disease,’ says Dr Mariana Vargas-Caballero of the Department of Physiology, Anatomy and Genetics, who led the work.

Mariana and colleagues looked at the strengthening of connections between mouse neurons in a dish, since the strengthening of connections in the brain’s neural circuits is thought to be how memories are formed and consolidated.

They found that amyloid β impairs the strengthening of the neural connections, or ‘synaptic plasticity’, although the nerve cells remained healthy in all other aspects that they could measure. But crucially, in neurons from mice engineered to have no tau protein, the amyloid β had no effect on this cellular model of memory.

‘This came as a complete surprise. It is a strong and reproducible effect,’ says Olivia Shipton of the Department of Physiology, Anatomy and Genetics, who is first author on the paper.

The team then went on to show that blocking the activity of tau using a specific chemical inhibitor also prevented the detrimental effects of amyloid β on the mouse neurons.

While it might be tempting to leap to the conclusion that this inhibitor could offer a promising avenue for the development of drugs to slow or halt Alzheimer’s onset, Mariana is more cautious. She says the stage the research is at is more about understanding the disease processes of early Alzheimer’s.

‘We want to know how amyloid β can lead to impaired synaptic plasticity as we can assume that this is like what happens in early Alzheimer’s disease. The findings should help us unravel the mechanism involved,’ she explains.

‘There is a huge gap in understanding what is relevant to the situation in humans. But we do now have a sensitive system to study what links amyloid β and tau, and tau and dysfunction in neural connections.

‘It is possible that pinpointing where in the chain of events tau is located could allow people in time to develop drug candidates to slow or stop the disruption of neural connections,’ she adds, but believes that more research is required to first understand the molecular pathways involving tau.

Mariana Vargas-Caballero is a Postdoctoral Training Fellow and Olivia Shipton is a DPhil student, both funded by the Wellcome Trust OXION initiative.

A novel way of finding people to take part in a new study of dementia is being employed by researchers from the universities of Oxford and London.

The Oxford Project to Investigate Memory and Ageing (OPTIMA) and the Centre for Stroke and Dementia Research at St Georges, University of London, will host stands at the Who Do You Think You Are? LIVE show, which starts 25 February at Olympia, London, where people interested in their ancestry will be enjoying ‘a weekend of discovery.’

The scientists are studying links between written language and dementia and looking for collections of text written by people with and without dementia.

They hope to make copies from diaries, letters, articles and books, written by the same person and ideally spanning three decades, to assess changes in the use of language by an individual and any links with the development of dementia. Changes detected could help diagnose Alzheimer’s disease earlier.

‘The types of people at the event are likely to be those who would keep records of their family history, family letters or journals,’ says Dr Celeste de Jager, Senior Research Associate in Neuropsychology at OPTIMA which is based at Oxford University’s Nuffield Department of Clinical Medicine

‘We want to interest people in the study because we need another 75 participants, each with a series of texts, to reach our target of 100.’ Dr Peter Garrard from St Georges is seeking a further 100 people for the same exercise. All copied text will be kept confidential and anonymous.

‘It isn’t the handwriting as such that’s important but the complexity of the text and use of language,’ Dr de Jager says. Deterioration in language is a common feature of Alzheimer’s disease and other forms of dementia. Loss of vocabulary and problems finding the right word are typical symptoms.

Writing samples for the study can be written or typed and must be from people of sixty years or older.

‘We will be looking for linguistic changes over time so need the same type of text from each person to have consistency,’ Dr de Jager says.

One person in five shows signs of dementia by the age of 80. Subtle problems may become apparent in spoken and written language before other symptoms such as memory loss are detected.