Features

We probably all know someone who has dementia. By 2025, there will be 1 million people affected by it in the UK. Alzheimer’s disease is well known as the most common cause of dementia. But what about the third most common cause of dementia, Dementia with Lewy Bodies (DLB)?

Dementia with Lewy bodies

Frederic Henry Lewy, a prominent Jewish German-born American neurologist, first described the phenomenon that came to be known as 'Lewy bodies' in 1912. These 'bodies' are clumps of a sticky protein called alpha-synuclein that build up in nerve cells in the brain, causing damage and eventually death to these cells. Typically, they affect the cells that control thinking, memory and movement. In fact, Lewy bodies are the underlying cause of several progressive diseases affecting the brain and nervous system, including not only DLB but also Parkinson's disease.

We tend to get rid of this particular alpha-synuclein protein quite slowly, using a sophisticated 'clean-up crew' of enzymes. Studies of the brains of people who have died as a result of DLB have shown that one of these sets of enzymes is abnormally increased in the cells that contain the toxic protein clumps.

On the face of it, this may not seem to be a problem, but the system of waste-disposal enzymes is a complex one. They each have different roles and work together to regulate the level of alpha-synuclein. One set of enzymes is responsible for directly attacking the protein, whereas another – the one that is abnormally increased in DLB cases – counteracts this action. This set of enzymes works to either elongate or trim off a tag on alpha-synuclein. This tag is made up of molecules of a small protein called ubiquitin, and its regulation goes awry in patients with DLB.

Targeting the abnormally increased enzyme

Associate Professor George Tofaris, together with his research group in the Nuffield Department of Clinical Neurosciences, is working on the development of targeted biological therapies in neurodegenerative disorders. George explains that when it works, this tagging system is essentially 'a kiss of death for proteins, but a kiss of life for the cell because it gets rid of unwanted or toxic proteins'.

Alzheimer's Research UK has allocated £50,000 to George and his team to investigate how the enzymes in the ubiquitin system might be targeted, in order to improve the disposal of alpha-synuclein. So how will the team go about this ambitious project over the next two years?

The first step is to work with others on screening the hundreds of possible chemical compounds that may have an effect on such enzymes in the test tube. Researchers will identify the structures of the compounds and make computational improvements in order to refine the list of compounds that will be used in the next stage of the experiment.

Moving on the second stage, George and his team will test the compounds on human brain cells. Researchers can create cortical neurons and dopamine cells – the brain cells affected by Lewy bodies – from skin cells, by using genes that regulate gene expression. This stem-cell technique is invaluable in allowing scientists to go straight from the test tube to working directly on a real human brain cell. The team will treat these brain cells with compounds and see which one has the most success in destroying the clumps of alpha-synuclein that can be triggered in these cells.

Neurological research such as this is mirroring the work that has been going on in the field of cancer for some time: targeting specific enzymes that have been identified in the lab as having a critical role in disease.

Paving the way for a new drug

After identifying an effective compound, the next step would be to test it in animals to see how the drug might affect the whole system, and to find out whether it can get through the blood brain barrier, a semi-permeable membrane separating the blood from the cerebrospinal fluid.

The good news is that even if this work doesn’t eventually result in a drug in tablet form, scientists will at least be in possession of good tools that can be used to manipulate alpha-synuclein and better understand how it is targeted for destruction.

Two of Oxford's museums opened late on Friday 30 October for Halloween-themed events. The Pitt Rivers Museum held an event called 'Day of the Dead' as part of its AfterHours series.

The evening explored how different cultures respond to death, focusing on mourning, memorialisation and celebration. The Ashmolean Museum ran an event called 'DeadFriday', as part of its LiveFriday series. The museum opened from 7pm to 10.30pm for visitors to enjoy talks, music and performances related to ghosts and spirits.

There were bite-size talks by over 25 Oxford Humanities researchers organised by The Oxford Research Centre in the Humanities (TORCH) at both events, exploring different objects in the museum's collections, as well as music, workshops and other live performances.

Professor Elleke Boehmer, Acting Director of TORCH and Professor of World Literature, says: 'One of TORCH's core strategic aims is to encourage interdisciplinary collaboration through fostering creative research environments.

'Museums are fantastic places to communicate research, engage with a wide range of amazing objects and reach out to the wider public - we were delighted to be a part of the Ashmolean’s DEADFriday and the Pitt Rivers' Day of the Dead event.'

The LiveFriday and AfterHours series have been notable for bringing a younger audience to the museum, and for allowing academics in the University to engage directly with the public. Dr Alexandra Lumbers, Academic Director at Jesus College, has attended several LiveFriday events.

She says: 'Generally I am not a huge museum-goer as I often find them a bit static but with the Live Fridays, it really brings the museum to life and really helps a wide variety of visitors to appreciate its treasures and understand them better.

It's great to see all from young children right through to quite elderly guests mingling and enjoying the evening together

Dr Alexandra Lumbers

'I really like the diversity of those who attend – it's great to see all from young children right through to quite elderly guests mingling and enjoying the evening together.

'There’s a great buzz with all the music, dance, interactive activities and that brings out the best in the museum and those who attend – it brings all these wonderful artefacts and treasures back to life.'

The World Series is the biggest contest in baseball so a lot is at stake for the New York Mets and the Kansas City Royals as they face off this week.

The contest has also divided two leading American historians at Oxford and Cambridge, who have come up with an unusual bet on the outcome of the match.

Professor Jay Sexton, director of Oxford University's Rothermere American Institute (RAI), is a Kansas native and diehard support of the Kansas City Royals. Gary Gerstle, the Mellon Professor of US History at Cambridge University, loves the New York Mets.

They have agreed that if Kansas City Royals win, Professor Gerstle will wear a Royals hat when he speaks at the RAI this January for the launch of his new book. If the Mets win, Professor Sexton will reluctantly wear a Mets cap.

'I am certain that all subjects of the British Royal family are siding with Oxford's Rothermere American Institute in this bet. Go Royals!', says Professor Sexton.

'People outside of North America often balk at the name "World Series". The hope is that this bet increases interest in Britain in one of the world’s most storied sporting events.'

Things are looking good for Professor Sexton so far, with the Royals 2-0 up in the best-of-seven series. The third game takes place tonight.

Oxford University's Wytham Woods were visited by a "National Living Treasure" last weekend.

No, Dame Judy Dench did not visit (as far as we know, anyway) but the University welcome famous Japanese potter Isezaki Jun, who has the title of the fifth National Living Treasure of Bizen, a place in Japan famous for its pottery.

Mr Jun launched the Oxford Anagama Project in the Woods on Saturday (24 October), when he began the loading of the Brick Anagama - one of two kilns that have been built over the past few months.

The first firing of the kiln will take place towards the end of November. But pots have already been produced from the first firing of the Willow Anagama.

Mr Jun also visited Keble College and gave a lecture at the University of Oxford Museum of Natural History.

At the lecture he said: 'I hope Oxford Anagama will give birth to a new conception of pottery and ceramics.

'The National Living Treasure is the preserver of important intangible crafts, in this case pottery. It preserves an ancient tradition.'

He said the Oxford Anagama project represents “another stage in Anglo-Japanese collaboration” and gives artists from both countries the chance to “learn from each other in a major international collaboration”.

'Where better to do it than Oxford?', he added.

The Oxford Anagama Project is co-directed by Dr Robin Wilson of the Wytham Studio at Wytham Woods and the School of Anthropology, and Jim Keeling of Whichford Pottery.

'It's certainly one of the more unusual interviews I've given,' said Professor Nicole Grobert, fresh from stepping out of a 1981 DeLorean being driven around a Surrey airfield by legendary broadcaster Peter Snow.

It sounds bizarre, but there was a point to it: October 21, 2015 was the date to which Marty McFly and Doc Brown travelled in Back to the Future II, and the BBC's Newsnight programme was keen to find out if the film's vision of the future had become a reality.

Nicole, a nanoscientist in the Department of Materials at the University of Oxford, talked to Peter (who, thankfully, didn't reach anywhere near the 88mph required to activate the flux capacitor…) about her work in a segment broadcast on Tuesday evening's Newsnight.

Speaking to Science Blog, Nicole said: 'Being interviewed in a DeLorean was surreal, scary and exciting. Almost crashing into a barrier added another boost of adrenalin. It was a lot of fun, but for now I'll continue working on the future of materials.'

Those materials are nanomaterials, which exist in a range of different shapes – including nanoparticles, nanotubes and nanosheets (for example graphene) – and are so tiny that we need modern techniques such as electron microscopy in order to see them. By definition, all nanomaterials are no bigger than 100 nanometres (100 billionths of a metre) in at least one direction.

Nicole said: 'The fact that nanomaterials are so small makes them special, because the properties of materials strongly depend on how individual atoms are arranged. In nanomaterials, with at least one dimension being below 100 nanometres, the ratio of the number of atoms that make up the surface to those that constitute the body of that material changes, in that there are more surface atoms that behave differently to those atoms in the bulk. As a result, nanomaterials become more reactive.

'Take gold, for example. Precious gold as we know it in the form of jewellery is heavy, shiny and does not change appearance with time. In contrast, gold in the form of nanoparticles can exhibit different colours depending on the nanoparticle size, and it can be used as efficient catalyst material in the chemical industry. The change in properties and behaviour of materials at the nanometre scale is purely owing to the change in size and the ratio of surface atoms to atoms located in the centre of the particles.'

She added: 'By manipulating the structure and composition of nanomaterials, their properties can be tuned further, and if we can find ways to produce these tailored nanomaterials in a controlled fashion, it will allow us to exploit their extraordinary properties.

'In theory, nanomaterials can outperform traditional materials. They can be highly conductive, lightweight and ultra strong. If we tackle current practical challenges related to manufacturing, characterisation, processing and handling, nanomaterials could be the answer to many of modern society's problems – not just in the areas of energy or health care.'

Nicole has already received some positive feedback from a mother whose daughter watched the Newsnight piece and has now decided she wants to become a nanoscientist.

Nicole said: 'I never saw myself as a role model until the day I gave a talk to school children at the Department of Materials open day, when a girl came up to me to ask me what she had to do to become like me. That was a bit of an eye opener. Since then, I've been actively trying to encourage both young women and men to get into or stay in the STEM subjects.

'As a supervisor, it is my personal goal to inspire students to think independently and take control over their projects from day one. Where possible, I also let students and post-docs shape their own projects, while providing them with a safety net in case things don't work out as planned. That's because I very strongly believe that developing independent research ideas and achieving personal success based on those ideas is key to building up the confidence necessary to follow one's dreams.

'Personally, I just followed my interests and was not put off by the fact there were so few female scientists around. I never even thought about it until I saw girls and young women react very differently to this fact.

'Needless to say, science and research are crucially important for society to survive, and, from my point of view, jobs in the STEM subjects are among the most versatile, inspiring, flexible and fun jobs around.'

Watch Nicole’s Newsnight appearance.