Features

Kwame Dawes, a leading voice in African and Caribbean poetry, has been appointed Visiting Professor at TORCH (The Oxford Research Centre in the Humanities).

Dawes is Chancellor’s Professor of English at the University of Nebraska-Lincoln, the Glenna Luschei Editor of the literary magazine Prairie Schooner, and a chancellor of the Academy of American Poets.

His many honours include the Forward Poetry Prize for Best First Collection, a Guggenheim Fellowship for Poetry, the Musgrave Silver Medal for contribution to the Arts in Jamaica, the Poets & Writers Barnes and Noble Writers for Writers Award, and a Pushcart Prize. In 2009 he won an Emmy Award for Live, Love, Hope, a multimedia performance poetry and music piece that explores the lives of people living with HIV AIDS in Jamaica.

His works of poetry, fiction, plays, and criticism include City of Bones: A Testament (2017), Duppy Conqueror: New and Selected Poems (2013); Bivouac (2010); She’s Gone (2007); A Far Cry from Plymouth Rock: A Personal Narrative (2006); and Bob Marley: Lyrical Genius (2003). He is co-founder and programming director of the biannual  Calabash International Literary  Festival in Jamaica, and founding director of the African Poetry Book Fund, which advances the development and publication of the poetic arts of Africa.

During his residency in Oxford in November 2018, Professor Dawes will launch an interactive exhibition that tells the story of the first five years of the African Poetry Book Fund, showing all that the fund has accomplished in its promotion and advancement of African poetry worldwide. The exhibit has been curated by Professor Lorna Dawes of the University of Nebraska-Lincoln and features the work of award-winning artist Walter Kitundi.

Professor Dawes will meet with students, scholars, teachers, and members of the local community in Oxford to talk about African and Caribbean poetry and literary criticism, university and school curricula, and ways to encourage, support, and promote marginalised voices in poetry. He said: ‘I look forward to the chance to have fruitful conversations about what I believe are exciting times for poetry, especially poetry from Africa. Technology, advanced communication and the challenges of a global worldview present us with challenges and great opportunities. My hope is to bring a holistic view to the discussion of the poetry of Africa.’

Elleke Boehmer, Professor of World Literature in English at the University of Oxford, who is hosting Professor Dawes, said: ‘TORCH is delighted to host Kwame Dawes on our Humanities and Identities programme. Professor Dawes is a true global intellectual with wide-ranging interests in the world literatures of the Caribbean, African America, and sub-Saharan Africa. He is currently involved in a history-making project to digitise African poetry past and present and bring this rich archive to global attention in ways that will traverse linguistic and cultural borders and draw in transnational communities of readers.’

Dr Katherine Collins, Leverhulme Early Career Fellow at the Department of Education at Oxford, who is co-hosting the residency with Professor Boehmer, said: ‘Professor Dawes is often called “the busiest man in literature” and we are thrilled he is going to be with us this month. His creativity across a range of different forms, and his ability to communicate his messages to an astonishing breadth of audiences, will make a significant contribution to ongoing discussions between scholars, teachers, and community activists on important issues of representation.’

TORCH Director Professor Philip Bullock said: ‘Kwame Dawes brings a unique perspective to bear on TORCH's Humanities and Identities programme, and reminds us of the crucial role played by art and creativity in the cultivation of a responsive moral imagination.’

The TORCH Humanities and Identities Programme is funded by the Andrew W. Mellon Foundation.

A new team of tour guides welcomed their first visitors at the Museum of the History of Science on Oxford’s Broad Street last week.

The volunteers, who have recently arrived in the city as forced migrants from countries including Syria and Iraq, will be running guided tours in Arabic of the museum’s famous collection of Islamic astronomical instruments.

The tours are part of Multaka-Oxford, a project at the Museum of the History of Science and the Pitt Rivers Museum, which creates volunteer opportunities in the museums and uses the collections as a meeting point to bring people together.

Multaka – which means meeting point in Arabic – aims to bring different perspectives to the presentation and interpretation of objects in two collections: Islamic Astronomical Instruments, and Textiles from the Arab World – recently donated by Jenny Balfour-Paul. It also offers people who have recently arrived in the UK the opportunity to practise their English, learn new skills and gain work experience.

Funded by the Esmée Fairbairn Collections Fund, and working in partnership with local community organisations including Asylum Welcome, Connection Support and Refugee Resource, the two-year project currently has a team of 26 volunteers, who have recently arrived from Syria, Iraq, Egypt, Zimbabwe, Sudan and Oman.

At the Museum of the History of Science, volunteer guides will deliver tours in Arabic, starting on 16 November at Oxford’s Christmas Light Festival. At the Pitt Rivers, volunteers will deliver tours from 2019 and will help select and label objects for a new exhibition, Textiles from the Arab World, which is due to open next April. Volunteers at both museums are also actively involved in collections research and documentation, organising events, writing a project blog and managing social media.

Multaka-Oxford builds on a long-standing partnership between the museums and local community organisations and groups. “Over the past seven years we’ve developed a good understanding of the role museums can play in supporting social inclusion and how we can collaborate with local organisations to support communities across Oxford,” says Nicola Bird, Project Manager for Multaka-Oxford.

Inspired by an award-winning project which has been running across four Berlin museums since 2015, Multaka: Museum as Meeting Point, the Oxford team have been working closely with their Berlin counterparts to create places where people can meet, share their experiences, knowledge and skills with each other.

Key to the success of the project has been a focus on what skills and experience the volunteers can bring and what they want to gain: an opportunity to learn and practise English, understand a new working culture, build self-confidence, meet new people and integrate into the local community.

'The project not only offers practical support such as on-the-job training, but also personal support such as providing a sense of inclusion,' says Nicola.

'We were delighted and happy when we found our heritage in Oxford,' says Abdullah Mohamad Alkhalaf, one of the volunteers. 'You gave us confidence in the practice of language and we are not just refugees but people working in their second homeland.'

Insulin is only half the story in what goes awry in diabetes...

More than 400 million people worldwide suffer from type 2 diabetes, a disease characterised by increased blood glucose levels, because the body’s normal way of controlling insulin release breaks down.

But insulin is only one half of the story about what goes wrong in type 2 diabetes: the release of another hormone called glucagon, which has an opposite effect to insulin, is also disrupted in type 2 diabetes.

Now a study led by Professor Patrik Rorsman from the Radcliffe Department of Medicine has found that exposure to high glucose levels for as little as 48 hours changes glucagon secretion from the pancreas – but there may be a way to reverse these effects to restore normalcy.

The study, published in the journal Cell Metabolism, used mice that had been genetically altered to mimic the symptoms of type 2 diabetes, as well as cells from the pancreas’ ‘islets’, donated by patients with type 2 diabetes.

‘Unique cells’

Endocrine cells, such as the alpha cells in the pancreatic islets, are excitable cells that can generate electrical pulses (known as action potentials), much like cells in the brain. Alpha cells and other pancreatic islet cells use these electrical signals to control the release of islet hormones (which include both insulin and glucagon). By studying the electrical behaviour of the alpha cells, Professor Rorsman’s research group (based at the Oxford Centre for Diabetes, Endocrinology and Medicine) hopes to understand how glucagon secretion is regulated.

“We actually use electrophysiology methods similar to those used by neuroscientists to record from these cells” said Dr Quan Zhang, one of the study co-authors.

‘There are only about 1g of pancreatic islets in the body and only 10% of these are alpha cells, so it’s quite a painstaking process to find and study them,” said Professor Rorsman. “Our group has really specialised in studying these cells, and we’ve probably studied more of these cells than any other group in the world!”

These alpha cells release a hormone called glucagon, which helps the liver to convert its store of glycogen into glucose, which then gets released into the bloodstream. The result is more glucose in the blood.

Insulin, which is also released by the pancreas, has the opposite effect: it signals the body to absorb glucose from the bloodstream, resulting in less glucose in the blood.

Normally, high levels of glucose result in pancreatic beta cells releasing insulin, so that glucose levels go down, and low levels of glucose result in the pancreatic alpha cells releasing glucagon, so that glucose levels go up.

“But this fine balance gets entirely disrupted in type 2 diabetes,” said Dr Jakob Knudsen, the first author of the study . “In type 2 diabetes, high glucose levels instead spur pancreatic alpha cells to release even more glucagon, which just makes glucose levels spike even higher.”

Blocking the cascade

But what is actually going wrong in alpha cells to produce this strange response? The research team studied this by tracking what happens to alpha cells exposed to high levels of glucose, using mice that had been bred to have changes similar to those experienced by patients with type 2 diabetes.

The team compared what happened in diabetic versus normal alpha cells, and found that exposure to high glucose levels for as little as 24 hours set off a complex cascade of cellular processes that led to more sodium being ‘pushed’ into the alpha cells.

This lowered the cells’ pH, which results in lower energy being available to the cell. The lower energy levels change the activity of an energy sensitive channel in the cell membrane, and ultimately result in the glucagon release going awry.

But crucially, the researchers were able to reverse too much glucagon secretion in both the cells and the mice by using a drug that stopped too much sodium from getting into alpha cells, thus blocking the chain of events that led to glucagon dysregulation right at the start.

High levels of glucose leave a mark

However, high levels of glucose still left their mark: overweight diabetic rats who had bariatric weight reduction surgery (similar to humans) or successful diabetes drug treatment still had protein changes in alpha cells caused by high levels of glucose - even after their glucose levels returned to normal.  What’s more, these protein changes weren’t restricted to the pancreas: the researchers found similar changes in heart and kidney cells in diabetic mice, even when their glucose levels had returned to normal.

“We’re still understanding the complex interplay that leads to diabetes, but we’re hoping that drugs that inhibit these protein changes might be one way of treating the disease,” said Professor Rorsman. “Indeed, we already know that some drugs with inhibit the ‘transporter’ through which sodium gets into alpha cells have had a positive effect in diabetes in animals – we think we now know why.”

“It is fascinating that something with such a small mass as the alpha cells, can have such a large impact on human health” said Dr Knudsen “We think that understanding the regulation of these cells both in healthy and diabetic individuals will improve our understanding of diabetes and provide new avenues of treatment for this growing patient population”.

• The paper is available to view here. 

By Professor Katrin Kohl, Professor of German Literature in Oxford's Faculty of Medieval and Modern Languages, and Director of the Creative Multilingualism project.

The report on the results of the Language Provision in UK MFL Departments 2018 Survey deserves to be read by everyone interested in the future of our discipline. It is the outcome of a collaboration between the AHRC-funded research programme Language Acts and Worldmaking, the Association of University Language Centres and the University Council of Modern Languages, and this in itself indicates welcome movement towards greater dialogue within the higher education system. The report is important not least because it highlights a conundrum that currently faces Modern Languages departments across the country (those which remain after years of attrition): what should our discipline be called?

The tradition of designating it ‘Modern Languages’ is rooted in the need to distinguish the young upstart from the ‘Classical Languages’ that provided the model for studying languages until well into the 20th century. Meanwhile schools prefer the name ‘Modern Foreign Languages’ – a designation appropriated in the title of this report. Is this what is being suggested as the solution? The focus on ‘foreignness’ buys into an agenda of ‘them’ and ‘us’ that is arguably unhelpful in a climate obsessed with borders designed to keep foreigners out.

Across the secondary and tertiary sectors, it is implicit that ‘ML’ or ‘MFL’ includes the cultures relevant to the languages taught, much as has always been the case with Classics. In universities, this distinguishes ML departments from Language Centres, which tend to focus especially on teaching practical language skills to students across disciplines. The difference in academic purpose often goes hand in hand with differences in perceived status and types of employment contract, and the picture is rendered more multi-faceted still by the fact that some Language Centres provide language teaching for ML departments. In schools, the tradition of teaching literature as part of MFL has weakened, and unlike university departments, which teach much of the cultural ‘content’ through the medium of English, school syllabuses focus on teaching in the target language.

And the complexity doesn’t stop there. Departmental names reflect not only academic traditions but also traditional hegemonies and colonial histories. To take Oxford as an example: the Faculty of Medieval and Modern Languages teaches only European languages and cultures, but it also embraces those countries in South America and Africa where the lingua franca is Spanish, Portuguese or French. Meanwhile a wide range of Asian languages is taught by the Faculty of Oriental Studies – a name that is justifiable only with reference to tradition and pragmatism. An African Studies Centre was established in 2005, but it does not offer undergraduate courses. And the Language Centre contributes significantly to the more than 50 ancient, medieval and modern languages taught across the University. 

In schools, too, ‘Modern (Foreign) Languages’ is traditionally associated only with European languages, although qualifications are available in a wide variety of ‘other’, ‘less-taught’ languages (fortunately, these qualifications were recently rescued from abolition). But the picture is beginning to change as schools become more obviously multilingual, and it is growing palpably illogical to distinguish between ‘Modern Foreign Languages’ as mainstream, and ‘community languages’ or ‘home languages’ as peripheral. Playgrounds are now audibly multilingual spaces where children are speaking languages from right across the world. This is not just the case in large cities – a local Oxford school has pupils speaking over 100 languages. Moreover, Mandarin is now supported by a prestigious government-funded Excellence Programme, and the report highlights that the ‘other’ languages, when combined, now show the highest numbers for A-level ahead of French, Spanish and German. This is not because they are ‘foreign’ languages but because they are rooted right here, in the UK.

So what’s in a name? Ultimately the identity, health and destiny of our discipline.

More than any other academic subject, Modern Languages suffers from a fragmented identity, unhelpful hierarchies and an inability to garner a true spirit of cohesion across sectors and language groups. If the discipline is to survive and make a vibrant contribution to schools, universities and society as a whole, the sectors and languages need to identify not just some common ground but a joint foundation. The discipline needs to address its identity crisis, reinvent itself, and find a unity that is strong enough to embrace diversity without falling apart.

Unpalatable as Brexit may be to many of us, it does provide incentives for promoting the value of all those languages that are spoken both beyond western Europe and within the UK. This need not mean sidelining the teaching of European languages for which we have the teaching expertise, and which underpin many of our closest intercultural relationships. Evidence suggests that fostering competence in one language will bring benefits for learning others, and indeed for one’s native language as well. But to enable our young people to enjoy those benefits, we need to promote language learning as such, and create a context in which every language matters, and can be a means of enriching one’s life, one’s career, and one’s potential to understand others. Languages are relevant to young people not because they are needed for booking a hotel, but because they are all around us, and fundamental to human relationships.

What, then, should be the name of our discipline? The Executive Summary of the report on Language Provision in UK MFL Departments concludes with a tentative preference for  ‘Languages’, and eloquently spells out the arguments for that choice:

“In an increasingly multilingual landscape, the survey responses present us with an invitation to reconceptualise our discipline, possibly under a unitary ‘languages’ label, dropping ‘modern’ and ‘foreign’ from its title to strengthen an agenda of inclusion and diversity, integrating all languages, ancient and modern, foreign and local, for those with and without disabilities, as well as a single voice for MFL and IWLP.” (p.7)

Settling on ‘Languages’ as the joint name and common denominator for the reconceptualised discipline would establish the foundation for a strong profile and vigorous public presence. The name would lend itself to embodiment in a website dedicated to promoting the interests of the discipline, providing essential information about ‘Languages’ across sectors, and establishing a hub for initiatives such as ambassador schemes and competitions.

Our model should be STEM – a unified concept coalescing around the promotion of the relevant disciplines in the education system, and formed from extreme diversity. It was invented in the 1990s, became established only in the 2000s and is now so successful that it is sweeping through schools and government policy-making as the only subject area worth studying. There is much that Modern (Foreign) Languages can learn from www.stem.org.uk. The first lesson is to rebrand itself with a simple name. ‘Languages’ even comes with the benefit of stating what’s in the tin.

By Melissa Bedard, MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine

October is a special time of year. The autumn leaves and crisp air mark the beginning of a new academic term. It also marks the annual announcements of the year’s Nobel Laureates, starting with the recipients of the Nobel Prize in Medicine and Physiology.

As scientists, we dream that our work today might revolutionise tomorrow – the kind of achievements that are recognised by a Nobel Prize. My research, like that of many immunologists, is primarily basic in nature. This year’s Nobel Prize in Medicine and Physiology is an exciting reminder that basic immunology discoveries can serve not only as key building blocks to better understanding fundamental immune cell function, but also as therapeutic targets in the fight against immune-mediated diseases.

From the lab bench to the clinic

This year’s recipients are Tasuku Honjo and James Allison for their discovery of PD-1 and CTLA-4 respectively. These two important molecules are expressed on the surface of T cells. Stemming from a branch of immune cells called lymphocytes, T cells have the ability recognise and kill unhealthy cells, such as virally infected cells, with a high degree of specificity. With a better understanding of how certain molecules, such as PD-1 and CTLA-4, control T cell function, scientists have discovered ways of manipulating T cell responses.

These findings laid the foundations for cancer immunotherapy, a revolutionary approach to treat cancer by enabling your own T cells to recognise and kill tumour cells. This strategy has dramatically changed cancer treatment, and has already benefited millions of individuals living with cancer. For example, before the implementation of cancer immunotherapy around 2010, the three-year survival rate for metastatic melanoma patients was just 10%. As of 2017, it was above 50%. Former American president Jimmy Carter received cancer immunotherapy for advanced melanoma that metastasised to the brain and is today cancer-free – just one example illustrating the power of cancer immunotherapy. Not only are patients’ lives extended, but they also have a better quality of life during treatment than with alternative therapies.

Tracing the immunology of cancer

To fully understand why cancer immunotherapy can be so effective, we must go back to fundamental immunology concepts. Immune cells can discriminate between the body’s own cells, termed ‘self’, and foreign pathogens, such as viruses and bacteria, termed ‘non-self’. Based on this discrimination,one’s immune cells will eradicate foreign pathogens while leaving the body’s own cells unharmed. However, the immune cells’ recognition of and response to tumours is a dynamic and complex matter. This is where the Nobel Prize-winning discoveries fit in.

There are several questions to consider when evaluating the immune response to cancer. Firstly, do immune cells infiltrate tumours? Immune cells extensively infiltrate so-called ‘hot’ tumours, whereas ‘cold’ tumours have few to no immune cells within the tumour tissue. Understanding why certain tumours are ‘hot’ while others are ‘cold’ is an intensive area of research, since immunotherapy, including that stemming from Honjo and Allison’s findings, would be most effective for treating ‘hot’ tumours.

Secondly, if present, are immune cells able to kill the tumour tissue? Even in ‘hot’ tumours, immune cells can be dysfunctional and therefore ineffective – an observation termed the ‘Hellstrom paradox’. Since immune cells are heavily influenced by their surroundings, the environment around the tumour might contribute to impaired anti-tumour immune responses. Certain signalling molecules, called cytokines, can shift the type of response mounted by immune cells. These cytokines act as messengers between cells and can be released from multiple cell types (immune and non-immune), including cancer cells themselves. One class of cytokines called interferons often promote tumour killing, while another cytokine, TGF-b, suppresses tumour killing. The relative abundance of such cytokines in the tumour surroundings can tip the balance between a pro- or anti-tumour immune response.  

Binding of specific receptors to PD-1 and CTLA-4 on the surface of T cells (the molecules discovered by the newest Nobel Laureates) inhibits T cell function. Under normal circumstances, PD-1 and CTLA-4 help turn off T cell responses to prevent over-zealous and damaging inflammatory responses (which can contribute to autoimmune diseases like certain types of diabetes). However, in cancer, where T cells must retain prolonged killing abilities, the use of antibodies to block the PD-1 or CTLA-4 interaction with their specific receptors on tumour cells boosts T cell activity so that they remain ‘tumouricidal’. This clinical approach is termed ‘checkpoint therapy,’ the most successful form of cancer immunotherapy to date.

Finally, if infiltrating T cells are effective, can they recognise specific markers on the tumour to kill it? Tumours arise for many reasons, but mutations in the genetic code of individual cells – mutations that cause the cell to multiply unchecked, often contribute to tumour formation. However, these mutations can lead to the production of mutated ‘self’ proteins that no longer resemble normal proteins, and as such immune cells recognise them as ‘non-self’. These mutated proteins are termed ‘neoantigens’ and can be recognised by specific T cells that kill the neoantigen-expressing tumour cells. Identifying and harnessing the power of neoantigen-specific anti-tumour responses is at the forefront of cancer immunotherapy research, especially after Steve Rosenberg’s research group used a cocktail therapy including neoantigen-specific T cells and checkpoint therapy to cure a woman with late stage metastatic breast cancer.

Future directions

Immunologists throughout Oxford, including those at the MRC Human Immunology Unit (MRC HIU) at the MRC Weatherall Institute of Molecular Medicine (MRC WIMM), are playing their part in advancing cancer immunotherapy research, particularly in addressing the three questions previously mentioned. Student-led research has centred on a molecule expressed by tumours that binds a receptor on T cells, similar to PD-1, which prevents T cells from infiltrating tumours. This interaction impairs T cells’ physical mobility by altering the cells’ actin cytoskeletons; collaborations between multiple labs in Oxford guided this research component. Other research also ongoing here in Oxford focuses on: (a) the affect of engineered antibodies against another inhibitory molecule, BTLA; (b) analysing tumour-specific T cell populations in melanoma patients over the course of their checkpoint therapy; and (c) fine-tuning the production of PD-1 on T cells to elicit effective anti-tumour responses while limiting a damaging inflammatory response.

Work at the MRC HIU also assesses how the tumour microenvironment contributes to anti-tumour immune responses. We investigate how immune cells are affected by stressful conditions, such as a lack of amino acids or oxygen. Based on these studies, we are assessing the therapeutic potential of manipulating metabolic enzymes differentially expressed in tumours versus immune cells.

Finally, there is ongoing and promising work on neoantigen discovery through understanding the mechanisms of neoantigen expression in ovarian cancer, melanoma, and glioblastoma multiforme, a type of brain cancer.

Final thoughts

All of this exciting immunology research, from basic mechanisms of immune cell function to translation studies, will contribute to a growing pool of knowledge that can guide therapeutic interventions for cancer. This year’s Nobel Prize in Medicine illustrates that basic discoveries in fundamental immunology paired with creative and aspirational thinking can have far-reaching implications for the future of medicine. Scientists at the MRC WIMM, including myself, had the pleasure of hearing Dr Honjo speak about his work last year. As compelling as his research was (and is), it was equally inspiring to see that Nobel Prize winners are fellow, hard-working scientists with the curiosity and appetite to see how far their ideas will go.