Scientists have long understood how oxygen deprivation can affect animals and even bacteria, but until recently very little was known about how plants react to hypoxia (low oxygen). A new research collaboration between Oxford University and the Leibniz Institute for Plant Biochemistry, published this week in Nature Communications, has answered some of these questions and shed light on how understanding these reactions could improve food security. Dr Emily Flashman, the lead author of the study and a research lecturer at Oxford’s Chemistry Department, breaks down the key findings:
Why is this study so important?
Most living things need oxygen to survive, including plants but flooding is a major threat to agriculture and vegetation. A plant's oxygen levels are jeopardised during a flood, and they basically can't breathe. To protect themselves from flooding and survive longer, plants have a built-in stress response survival strategy, which re-configures their metabolism and supports them to generate more energy.
Scientists knew about this stress response, but they didn’t know exactly how it was controlled. Our research underpins not only an understanding of how plants respond to loss of oxygen, but also how this response could be manipulated to protect them long term. With climate change of increased prevalence in today’s society, flooding is a constant source of concern, so it is even more important for us to understand how hypoxia affects plants and crops, so that we can find new ways to preserve and protect them from it. Manipulating the enzymes involved in the process may help us to cultivate new crops and even to weather-proof them.
How does this reaction affect them?
When oxygen is in short supply a plant’s stress response effectively shuts down its metabolism, and activates an alternative pathway that allows it to live for a short amount of time, with reduced oxygen. During this time the plant has much less energy, but is still able to survive and function on a basic level. Much like when someone holds their breath underwater, their oxygen reserves allow them to survive for a short amount of time, even though they cannot breathe in fresh oxygen.
Our research underpins not only an understanding of how plants respond to loss of oxygen, but also how this response could be manipulated to protect them long term. Manipulating the enzymes involved in the process may help us to cultivate new crops and even to weather-proof them against climate change.
What was the aim of your research?
We wanted to analyse this process, and understand how the enzymes that trigger it work. Once you know this information, you can then work out how to inhibit the enzymes and control the flood response pathway, and in doing so, keep the plant alive for longer. The overall aim being to genetically modify crops to make them flood tolerant. Understanding how these processes work is the first step in achieving this. Until now the molecular details of the plant stress response to hypoxia were not proven, but our research changes this.
Scientists understood that a plant’s response to hypoxia is controlled by ERF transcription factors, proteins which trigger changes in gene expression. In turn, the stability of the ERFs is controlled in an oxygen dependent manner by a set of enzymes, the Plant Cysteine Oxidases (PCOs). The PCOs speed up the break down (degradation) of these transcription factors, via one of the cell’s protein removal and recycling systems, called the proteasome.
Crucially, our research showed how PCOs use oxygen to work, and how this allows the ERFs to be recognised by the next step of the degradation pathway. Thus the whole pathway needs molecular oxygen to work. So in times of regular oxygen supply, the ERFs are degraded before they reach the cell nucleus and before they can activate the stress response genes. However, when oxygen is limited, as is the case during flooding, the PCOs cannot work, efficiently, so the ERFs will not be flagged for degradation and can activate the hypoxic stress response required for the plant to survive.
With climate change causing increasingly frequent flooding events worldwide, understanding how crops respond to flooding is important, in order to control or manipulate the process.
How can the findings be used to improve food security?
With climate change resulting in increasingly frequent flooding events worldwide, understanding how crops respond to flooding is important, in order to control or manipulate the process. Our research supports the understanding of this response on a molecular level – down to the role played by individual enzymes in the process. Stabilising the ERF transcription factors has been shown to enhance flood tolerance, so the targeted inactivation of the enzymes that regulate its stability may assist in cultivating crops that are able to withstand flooding longer and more efficiently.
How can the findings be built on in the future?
Now we understand what the enzymes do, we are looking further into the details of their structure and mechanism to understand precisely how they work. This will help us target the most effective way to manipulate them to artificially inhibit their activity and enhance ERF stability, first using the isolated components of the pathway before testing in plants.
Few might connect volcanic eruptions with the eighteenth century arts and weather change, but with its varied collection of artefacts, Volcanoes, the captivating exhibition currently running at Oxford’s Bodleian Weston Library hopes to change that. ScienceBlog met with Professor David Pyle, volcanologist and the exhibition’s curator, to find out more about how he is challenging people’s perceptions of volcanoes, and how they impact the world around us.
What was the inspiration behind the exhibit?
About three years ago, Richard Ovendon, who is now the Bodleian’s Librarian, and Madeline Slaven, Head of Exhibitions floated the idea of doing something on the theme of volcanos. This sounded like an exciting opportunity and we took it from there.
On a personal level, my work tends to focus on the geology of volcanoes, but recent projects in Santorini, Greece and St Vincent in the Caribbean, have looked at other records of volcanic activity. People’s stories and official accounts of the effects of volcanic eruptions tend not to be included in formal science evaluations, but they can tell us a lot about their human impact. The exhibition was as a great opportunity to share this perspective and surprise people.
What kind of insights can these records offer?
The colonial records of the St Vincent eruption of 1902 are extraordinary. One thing the colonial government was good at was keeping records, and this includes correspondence between the Governor, Chief of Police and other high level officials in London. The detail you can extract from official first-hand accounts, in terms of what actually happened, and how the eruption impacted communities, opened my eyes to the wealth of information available on how people have coped with and responded to volcanic activity in the past.
Instead of just focusing on explorers’ experiences we have included elements that shed light on tourists’, travellers’ and everyday people’s encounters with volcanoes – even those who came across them by accident.
How did you decide what to include?
I looked through around 400 objects in total, and the final exhibition features 80. Everyone had a role to play, and I spent three years burrowing through the Bodleian archives.
As a volcanologist, I was in my element and found the volume of material incredible. Handling old books and manuscripts evokes a tangible connection between you, now and then, it’s an immense privilege to hold an object with such tremendous history.
I’m not sure what other people expect when they come to an exhibition called volcanoes, but I imagine people would envision vivid colours and descriptions of violent eruptions. The vivid colours are carried through the exhibition in its design, but the arts’ pieces selected show that volcanoes have had an entirely different impact socially. Instead of just focusing on explorers’ experiences – which are well documented, we have included elements that shed light on tourists’, travellers’ and everyday people’s encounters with volcanoes – even those who came across them by accident.
Can you tell us about the structure of the exhibition?
There are 10 differently sized cases in the exhibition - small, large, long, 3D etc. Of course we have the Bodleian’s printed materials (books and manuscripts etc.) and physical rock samples from the Museum of Natural History, but it also features things that you might not expect; Victorian poetry, art, film posters, match box lids and even tourist trinkets.
Which display are you most pleased with?
The volcano weather exhibit surprises people. An eruption takes place thousands of miles away, but its impact is often felt across the globe, through climate change. From fiery sunsets, to torrential storms, they have had great impact on the weather of the natural world. On the one hand there is the devastating immediate impact on the people living around the eruption, and then millions of miles away, the effect socially was entirely different, and often quite sublime.
An after effect of the eruption of Mount Krakatoa in 1883 were spectacular sunsets across Europe. These sunsets were the inspiration for some of the most celebrated poetry of the time, such as Tennyson and Gerard Manley Hopkins, and stunning watercolour paintings.
People might not connect art and volcanic experience, but the sheer volume of material inspired by them, tells us a lot about international communication in the 18th century. The international telegraph network meant telegrams could be sent quickly across continents. Whether people experienced eruptions first hand, or heard about them on the social grapevine, they clearly developed their own feelings about them and expressed them in memorable ways.
The weather diaries are fascinating, and show the impact of climate change physically and socially, at a time when no one really understood what it was.
Do any of the pieces tell us anything particularly interesting about how perceptions of volcanoes have changed?
The weather diaries are fascinating, and show the impact of climate change physically and socially, at a time when no one really understood what it was.
One from 1783 details the aftereffects of an eruption in Iceland, which triggered a hazy smog, so thick it could almost chock you. The diaries build a picture of an unbearably hot climate, complete with violent thunderstorms and an unusually red sun. Fast forward a few hundred years and we recognise these unusual weather conditions as air pollution induced climate change. But, at that time no one really knew about it, or had an explanation for the unusual weather, the explanations came later.
Another focuses on the impact of an eruption in 1816, which became known as the year without a summer in Northern Europe. In the Northern US conditions were so bad, it was dubbed: “Eighteen hundred and froze to death.” From the same period we have two pages of Mary Shelley’s diary, who of course wrote Frankenstein. She’s writing from Switzerland, in July 1816 - one of the worst affected places. Making these connections goes some way to explaining the morose tone and scenery depicted in the book, and the literary impact of eruptions.
Favourite piece from the exhibit?
One of the most significant elements is the oldest, a carbonised scroll from Herculaneum, located in the shadow of Mount Vesuvius. It is a piece of papyrus that contains a book that would have been rolled up and stored in a library in Herculaneum. It was buried by and preserved by the eruption of Vesuvius in 79AD. When the library was excavated in the late 1750s, the King of Naples gave away some of these scrolls to passing dignitaries, one of whom was Prince George of England, who then gifted the scroll to the Bodleian Library.
There is something quite special about holding a volcano exhibition in a library, where the oldest item in the show is also from a library, and was preserved because of a volcanic eruption.
Storytelling is a powerful way of communicating how volcanoes behave, and starting conversations about how society can prepare for an unexpected eruption.
How did you come to be a volcanologist?
I saw my first volcano aged seven, when my family lived in Chile for a year, and I have been obsessed ever since. It’s a place where you can’t escape mountains and there are volcanoes everywhere, including my favourite, Villarrica. I’ve been back as adult, and fulfilled my childhood dream of climbing the summit and peering into the crater.
What is your proudest achievement to date?
An academic’s career is long and potentially lonely, so you have to celebrate everything along the way. I don’t look back on anything that I have done with rose tinted spectacles because there are so many things that I want to do next.
I have been very close to the exhibition for a long time, and now we have finally opened, it is delightful to see other people enjoying and responding to it.
What is next for you?
My next project focuses on better telling and sharing people’s stories and experiences of volcanoes. Storytelling is a powerful way of engaging with people, communicating how volcanoes behave, and starting conversations about how society can prepare for an unexpected eruption. The official records of the St. Vincent eruption are a great testament to events, but they are not easily accessible to people actually living on the island, so impossible for them to learn from.
Storytelling is a powerful way of engaging with people, communicating how volcanoes behave, and starting conversations about how society can prepare for an unexpected eruption.
In collaboration with researchers from the University of East Anglia, who are leading a project on strengthening resilience in volcanic areas, we have been running workshops on the island, speaking to residents about their own experiences, and sharing our research.
Like many other Caribbean islands there are much more pressing needs - annual hurricane season being one of them. The volcano hasn’t actually erupted for forty years, so we were expecting it to be low on their list of priorities, but actually people have been really engaged and eager to think about it. Particularly the difference between dealing with an eruption today and forty years ago.
What is your favourite thing about your job?
It is a huge privilege to be able to work in places that are so captivating, visiting them with a purpose other than just travelling there for the sake of it. There are 60 or 80 volcanoes that erupt in any year, and often they are totally unexpected, so there is always something new to learn and look at.
• Volcanoes is running at the Bodleian Weston Library, Oxford until 21 May 2017
‘I would not be a teenager again if you paid me.’ If this statement perhaps sounds familiar, it is with good reason.
When people reflect on their teenage years it is not always in the fondest context. Along the journey from childhood to teenager, and then finally, onto adulthood, the brain changes in a lot of ways. Known as the control centre of the human body, the brain is responsible for our thoughts, actions and how we function in general.
Researchers at the University of Oxford have been working to understand this pivotal developmental period and a new animation from Oxford Sparks, the University’s popular digital science portal, has shone a light on this project. The animation offers a glimpse inside the teenage mind, and highlights the team's efforts to understand these developmental changes, and how much they influence peoples' behaviours during this time.
During this time three key changes take place, that combined, go some way to explaining the rollercoaster of emotions experienced during adolescence:
- Development slows down in the parts of the brain that control our attention span, impulsive behaviours and the ability to both resist distraction and make decisions;
- Increased development and functional ability in the areas of the brain that control people's 'gut reactions', such as emotions, appetite and mood;
- The communication ('cross-talk') between these parts of the brain becomes increasingly efficient.
In terms of brain development, adolescence represents a ‘perfect storm’ for teenagers, which explains some of the highs and lows associated with the period. These include, the pitfalls of taking more risks and increased social anxiety or, on a more positive note, the desire to try new things and have more experiences.
View the video within the context of your own teenage years here:
As Associate Professor of Organic Chemistry, a mother of two and one of Oxford University’s most successful entrepreneurs, developing both the spinout companies MuOx and OxStem, Professor Angela Russell wears many hats. She met with ScienceBlog to discuss the progress of women in science in the 21st century, her journey from academia to a successful business woman and her advice to anyone following in her footsteps.
What does your work in Organic Chemistry involve?
I run an academic research group aiming to develop new drugs to treat devastating degenerative diseases like Alzheimer’s and heart failure. The technologies we develop are helping us to answer fundamental clinical questions and understand how different substances affect regeneration processes in the human body. Our work is incredibly rewarding and has the potential to positively impact millions of peoples’ lives.
Has becoming an entrepreneur always been a goal for you?
I always thought I would be a pure academic scientist, so the business side of things was totally unexpected. Often when you make a scientific discovery the most exciting part of the project is seeing it applied, but it easy to become removed from the development process in academia, and, it got me thinking why not just do it myself?
How did your journey into science commercialisation evolve?
I have co-founded two successful Biotech companies and both evolved quite organically. Mentorship has been key. Professor Steve Davies in particular has been a huge influence on my career and a co-founder of both MuOx and OxStem. As an entrepreneur himself, he has always encouraged me down the road of the commercialisation of science.
How did you go about commercialising your research and developing a spinout company?
MuOx (Muscle Oxford) built on a longstanding collaboration with Professor Dame Kay Davies, looking for a new treatment for Duchenne Muscular Dystrophy. Our original findings had led to the formation of VASTOx (now Summit Therapeutics plc) who developed the drug ezutromid into clinical trials. We wanted to discover new drugs that could improve on ezutromid’s effectiveness and went back to designing new substances that took the original research to the next level; MuOx.
Often with spinout development selling your product can be a real challenge, but our ongoing relationship with Summit meant they bought us very quickly. The company was spun out in 2012 and bought for five million pounds, by Summit in 2013. We continue to run an extremely important collaborative research programme with Summit developing these new drugs for Duchenne Muscular Dystrophy.
The technologies we develop are helping us to understand how different substances affect regeneration processes in the human body. Our work is incredibly rewarding and has the potential to positively impact millions of peoples’ lives.
What was the biggest learning curve from the development?
Building a strong case for product development that can be easily communicated to anyone - scientists, investors and general public alike is not easy. But if you don’t get it right, you won’t get the investment. As scientists, we get used to talking to each other in scientific code, but it’s just jargon to anyone else. People can’t support or engage with something they don’t understand, so I had to learn quickly how to communicate to people with varying science knowledge, like patients and the general public. You have to build an exciting case and believe in it yourself: ‘not only is this exciting science, but we can deliver on it and change people’s lives.’ If you don’t believe in your product why should anyone else?
How did OxStem evolve?
MuOx proved that we could translate science effectively, and it gave me the confidence to go for it on a big scale with Oxstem, which was effectively MuOx 2.0. It is exactly the same premise, a company developing drugs to treat diseases. But where MuOx focused specifically on muscle degenerative disease, OxStem aims to develop a platform to treat any degenerative or age-related disease.
Was building the company very different the second time around?
Oxstem isn’t a single company, it is an umbrella company, and we spinout successful daughter subsidiaries, each with a different disease focus – four so far. As an academic research development, it has been hard and time consuming to communicate the value of this structure to university stakeholders. We had to outline the structural benefits and challenges, such as how the model could work within existing financial structures, management of intellectual property and so on. It took a long time, but we achieved our goal, and in May 2016 we hit our £17 million target needed to get the company off the ground.
What was the biggest challenge you faced setting up a spinout?
Getting people to believe in your idea in the early stages is really difficult, particularly with funders. Investment is essential to progressing opportunities from lab experiments, to something that will be of benefit to patients in the long run. It takes a lot of time and patience and you have to be up front with people, making sure that they understand what they are getting into. Yes it is a lucrative investment opportunity, but there are risks.
What advice would you give to someone looking to commercialise their research?
Identify a clear market need for your product, make a clear development plan and a list of reasons why you are the only one that can deliver on it. That is the way to be successful. Being actively involved in progressing your research is so rewarding. If you truly believe in your idea, this is the route for you.
Generally getting government or charity funding for discovery science is straight forward, but doing so for an idea that you want to translate into a research led, spin-out is not so easy; dubbed the “valley of death”. You have to have proof of concept, and show that your idea is going to work.
What projects are you currently working on?
The bulk of my work focuses on the development of new drugs to tackle degenerative and age-related diseases. For instance in collaboration with Professor Francis Szele we are looking at treating diseases like Alzheimer’s and other neurodegenerative conditions and how symptoms can be reversed. A disease like Alzheimer’s is characterised by the progressive loss of neurones in the brain, and we are working to develop a regenerative treatment that will replenish these neurones, reversing the symptoms of the condition in the process. It will make a tremendous difference to people’s lives. If all goes to plan, we will be ready to run a clinical trial in the next three to five years.
You have to build an exciting case for your product, and believe in it yourself. If you don’t believe in it why should anyone else?
Has being a woman in science posed any specific challenges for you?
I have never been discouraged or made to feel that I can’t achieve things because I am a woman. Nor have I ever felt it was an advantage either. I think that is really important. We can’t solve gender bias against women, by deflecting it to men. We have to create an environment where it is better for everybody. I am heavily involved in the Athena SWAN Charter, self-assessment process, and it’s not about creating more opportunities for women, but for everybody, and achieving equality across the board.
How do you think these opportunities can be created?
I think we have to change the working culture, and focus more on valuing people for what they contribute, not how long a day they work. In the past there was a more blinkered view that a brutally long working day was the only way to succeed, which made managing a family and a career almost impossible, but that is changing.
We can’t solve gender bias by deflecting it to men. We have to build an environment that is better for everybody. Not just creating more opportunities for women, but achieving equality across the board.
What motivated you to become a scientist?
My dad was always supportive of my ambitions. When I was 14 he told me ‘you’ll never be happy with a desk job.’ He was right. I’ve always been driven by a desire to carry out research for the betterment of human health. Chemistry was a subject I absolutely loved at school and saw as fundamental to all science because it underpins and impacts so many other disciplines, including medicine.
What advice would you give to someone embarking on a career in STEM?
The decisions that you make at the beginning of your career are important, and can impact your whole future, so try and think long term wherever possible. Everyone makes mistakes, but recognising when you aren’t on the right track and correcting it quickly makes it easier to stay on course. I came to Oxford to study Biochemistry, but realised quickly that it wasn’t for me. Two weeks before my first year exams I told my tutor I wanted to change to Chemistry. I flipped straight into the second year of a Chemistry degree, and almost gave my tutor a heart attack, but it was exactly the right decision for me.
If you hadn’t been a scientist what was your plan B?
I would have been a chef. I actually think chemists and chefs have a lot in common. They experiment with flavour combinations and we scientists cook up drugs that we want to use for clinical use. There is nothing more rewarding than cooking a nice dinner and watching your children tuck in.
In a guest blog, Dr Oliver van Hecke, DPhil student in Oxford University’s Nuffield Department of Primary Care Health Sciences and Oxfordshire GP, explains why genetics may determine whether someone experiences multiple chronic diseases.
Chronic pain, depression and heart disease are three of the commonest causes of disability, and are becoming more prevalent in the population. Increasingly, some people will suffer from one or several of these long-term health problems in their lifetime, which is known as multimorbidity, but why? Is this simply down to bad luck or could there be an underlying cause, perhaps due to a shared familial risk, and/or genetic factors?
While we know that age, gender, social circumstances and lifestyle increase someone’s vulnerability to multiple causes of disability, research has now revealed that genetics can indeed play a role in determining whether someone experiences multiple chronic illnesses.
The new study, which we were involved with along with colleagues at the University of Dundee and Kings College, London, examined two major existing population cohorts (Generation Scotland and TwinsUK), for the likelihood of chronic pain, depression and heart disease co-occurring in both individuals and in their siblings. We found that people who had one of these illnesses were much more likely to have one or both of the other illnesses.
Interestingly, we identified a sibling link – the brothers or sisters of people with one of these illnesses were much more likely to have one of the other illnesses too, even after allowing for known social and demographic factors. For example, siblings of people with heart disease were twice as likely to have chronic pain, while siblings of those with depression were twice as likely to suffer from heart disease.
Using the twins data, we were able to show that genetics contributed to the co-occurrence of chronic widespread pain and heart disease in twins, in addition to important environmental contributions.
The finding that genes likely play a key role in determining whether someone experiences multiple chronic illnesses provides researchers new avenues to explore the underlying biological mechanisms between different conditions. Of course, as both a researcher and a clinician I realise it will always be important to address the social and demographic factors that cause disability and comorbidity, such as deprivation for example. However this new insight into the shared genetics of comorbidities may enable us to recognise these conditions earlier in the community. This would, in turn, allow us to focus on preventative therapies for these patients by targeting the underlying causes (such as stress or health inequalities) rather than the visible symptoms of the condition itself.
The full study, ‘Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study,’ can be read in the journal PLOS ONE.
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