Watch a short video about Dr Jason Bruce’s research into Pancreatic Cancer.
Circadian clocks are found across all higher species, controlling daily rhythms of behaviour and physiology. The clocks are thought to tick by the continuous creation and degradation of clock proteins in a 24 hour cycle. The principle clock in humans is the suprachiasmatic nucleus (SCN) which is governed by Period genes (Per1, Per2).
Recent research by The University of Manchester and The University of Cambridge has dispelled the previous theory that in mammals Per 2 is let in to the cell nucleus by a ‘gate’ from the outer cytoplasm. Previous studies in fruit flies had shown that Per2 builds up in the cytoplasm until it reaches a critical level at which point the gate would open, allowing it to enter the nucleus.
It is this movement from cytoplasm to nucleus that dictates the tempo of the fly’s body clock.
According to Professor Andrew Loudon from The University of Manchester, this gated mechanism found in flies does not happen in mammals. Instead, the protein moves from the cytoplasm to the nucleus straight away.
Professor Loudon said:
“We have discovered that the level of the per2 builds up in the nucleus and it is this build-up of protein that gives the clock its rhythm.
This is an important advancement in our understanding of the body clock at the cellular level.
As new insights into how our body clocks function are discovered, drugs are being developed which will effectively target the mechanism responsible for circadian imbalances.
We think that this non-gated system is likely to be susceptible to drug intervention – but clearly more work is needed on that front.”
Disorders of the circadian clock, ranging from jet-lag, through shift-work to sleep disorders associated with ageing, dementia and psychiatric illness have a major impact on our health. This work went on to show how particular drugs affect the behaviour of the clock proteins and could provide a first approach to developing suitable therapeutics to treat sleep disorders.
The work was funded by the MRC and BBSRC.
The University of Manchester was recently a finalist at the Biotechnology and Biological Sciences Research Council (BBSRC) Excellent with Impact awards and was awarded two special commendations for demonstrating outstanding practice in particular areas. The University of Manchester was awarded the two special commendations for our outreach in collaboration with the Manchester Museum and effectively embedding impact across our staff development programmes.
The awards looked to “recognise institutions that can develop and successfully deliver a vision for maximising impact, alongside a relevant institution-wide culture change” and so The University is extremely proud to be commended in such a way.
The BBSRC is the largest biology funding body in the UK and they support over 3,500 scientists in the UK. The University has a large number of BBSRC-funded lab groups performing cutting edge research across all its Faculties. Our commendations and presence in the finals recognise the importance our groups place on research that has a real impact and is setting a culture of excellence.
The BBSRC judges were particularly impressed with our Museum outreach, highlighting the ‘Learning with Lucy’ frog conservation and education programme. Working with the Manchester Museum, the Faculty teamed up with Lucy, a nine year old girl on a mission to save the Lemur Leaf frog. The project was a huge success, reaching international coverage and having an impact in helping to save one of the world’s rarest frogs.
Professor Amanda Bamford says
” I am really pleased the judges were impressed with the education and outreach work we do with Manchester Museum. We have a very long standing, successful and unique collaboration with the Museum staff delivering outstanding impact”
In addition, two University scientists, Dr Sheena Cruickshank and Dr Andrew Almond, were finalist for BBSRC Innovator of the Year this year. Innovator of the Year “celebrates individuals and small teams who have harnessed the potential of their excellent research to help address real world challenges”.
Professor Simon Hubbard, one of the leaders of the University competition bid, says
During the course of this three year competition the University has made great strides in embedding an impact culture into its staff and students, in all areas from business development through to social responsibility. I am thrilled that the BBSRC recognised this and chose us as one of the 10 finalists. We were the only institution to have two nominees for Innovator of the Year and were rightly recognised with two commendations for our impact success.
The first detailed study of a Stegosaurus skull shows that it had a stronger bite than its small peg-shaped teeth suggested. The Natural History Museum’sStegosaurus specimen, ‘Sophie’, has been compared with two plant-eating dinosaurs with similar skulls:Plateosaurus and Erlikosaurus.
All three had a large low snout and a scissor-like jaw action that moved up and down. Using computer modelling a team of scientists from Bristol, London, Manchester and Birmingham, including Charlotte Brassey from The University of Manchester, has shown these dinosaurs had different biting abilities.
As Prof Paul Barrett, dinosaur researcher at the Natural History Museum explains: “Far from being feeble, as usually thought, Stegosaurus actually had a bite force within the range of living herbivorous mammals, such as sheep and cows.”
The finding means that scientists need to reconsider how Stegosaurus fitted into its ecological niche. For example it may have had a role in spreading the seeds of woody evergreen cycads.
Stegosaurus lived around 150 million years ago and needed to eat a lot of plants to sustain its large size. As grasses did not exist then, it would have fed on plants such as ferns and horsetails.
As Barrett, leader of the research team, comments: “Our key finding really surprised us: we expected that many of these dinosaur herbivores would have skulls that worked in broadly similar ways. Instead we found that even though the skulls were fairly similar to each other in overall shape, the way they worked during biting was substantially different in each case.”
Lead author Dr Stephan Lautenschlager, a post-doctoral researcher at the University of Bristol’s School of Earth Sciences, employed digital models and computer simulations to analyse the dinosaurs’ bites, using data from 3D scans of the skulls and lower jaws. He used engineering software to give the skulls the material properties that would match as closely as possible to the real thing, for example, using data on crocodile teeth to model those of the dinosaurs.
By attaching muscles to the models, he was able to examine the forces that the jaws could produce and the subsequent stresses on the skulls.
As computer power increases and software becomes more available, Lautenschlager thinks that we will see more modelling used in dinosaur research: “Using computer modelling techniques, we were able to reconstruct muscle and bite forces very accurately for the different dinosaurs in our study. As a result, these methods give us new and detailed insights into dinosaur biology – something that would not have been possible several years ago.”
Further images are available at https://nhm.box.com/s/fnaf66vdo8bbrekfilwu3b7di8q327zf Please note: images are for single use only to illustrate this press release and are not to be archived.All images © Stephan Lautenschlager
Original PublicationLautenschlager, S., Brassey, C. A., Button, D. J., Barrett, P. M. Decoupled form and function in disparate herbivorous dinosaur clades. Sci. Rep. 6, 26495; doi:10.1038/srep26495 (2016)
“We can send a man to the moon, so why can’t we beat cancer?”
Just a few years ago, we at last reached the point where half of all people diagnosed with cancer could expect to survive it. Within 20 years, scientists hope that figure will rise even further to 3 in 4 people.
Reaching these milestones does not happen easily. It is the culmination of years of research by thousands of scientists around the world, working in fields as diverse as genetics, pharmacology and biochemistry – as well as medicine.
Much of this research takes place here in Manchester. In fact, cancer is one of The University of Manchester’s five main ‘research beacons’ – priority research areas in which we are world leaders – the others being industrial biotechnology, advanced materials, energy and addressing global inequalities.
Beyond the main university campus, we also have the Cancer Research UK Manchester Institute, situated over the road from the Christie Hospital in Withington, south Manchester. Their brand new £28.5 million building opened its doors last year, and is jointly funded by The University of Manchester, The Christie NHS Foundation Trust and Cancer Research UK.
Cancer Research UK is the world’s largest independent cancer research charity, and funds and conducts research into the prevention, diagnosis and treatment of the disease. Its work is almost entirely funded by donations from the public.
The Christie Hospital is one of Europe’s leading centres for cancer treatment and research, treating over 40,000 patients a year, and around 400 early phase clinical trials are taking place here at any one time. This makes The Christie an ideal next-door-neighbour for the new Cancer Research UK Institute.
Research in places like Manchester has vastly improved our knowledge of cancer and how we can treat it over the past decades. The discovery of epigenetics has shone a new light on the different ways this disease can arise, while genome sequencing has given us new and highly effective methods of diagnosis, allowing us to accurately tailor treatments to each individual’s needs.
There’s still such a long way to go however.
Cancer is not one disease nor one hundred diseases but many thousands, each unique and requiring a different response. Such a diverse assortment of diseases is only possible because the body itself is so diverse.
37 trillion cells, and 10,000,000 components per cell make the body 125 billion times more complicated than the Saturn Rockets that allowed humans to go to the Moon. It is only when we consider this staggering complexity that we can begin to appreciate the immense challenge we face in trying to treat the numerous different types of cancer.
A ground-breaking study by scientists from the Faculty of Life Sciences and The University of Liverpool scientists has been published in the journal eLife and has identified a new link between inflammation and cell division.
Two of the most important processes in the human body, their accurate control is a holy grail for scientists researching the prevention of infection, inflammatory disease and cancer.
Professor Mike White, who led the BBSRC-funded research and investigates how cells adapt to signals in the body, hit upon the discovery using advanced microscopy and mathematical modelling at the University of Manchester’s world-leading systems microscopy centre and the University of Liverpool’s Centre for Cell Imaging.
“This is an exciting discovery: for the first time we find a link between the system which regulates how cells divide and the basis of some of medicine’s most intractable diseases,” he said.
Inflammatory signals produced by a wound or during an infection can activate a protein called Nuclear Factor-kappaB (NF-κB), which controls the activity of genes that allow cells to adapt to the situation.
Incorrect control of NF-κB is associated with inflammatory diseases, such as Crohn’s disease, psoriasis and rheumatoid arthritis; it has also been linked with ageing and some cancers.
A key way in which human cells adapt to signals in their environment is by dividing to produce new cells through a repeating pattern of events, called the cell cycle. A cell first makes copies of its DNA, in a stage known as the DNA synthesis phase, and then divides into two daughter cells.
The cell cycle is controlled by a family of proteins called E2 factors, which control the start of the new cell’s DNA synthesis phase.
In the eLife study, the team showed that the NF-κB and E2 factors bind to each other in the cell. This controls the level of the NF–κB signal, which is enhanced just before DNA synthesis, but reduced during the DNA synthesis phase.
They also show that signals which activate NF-κB can change the timing of cell division.
The work used a set of mathematical equations to make predictions about cell responses, which were then tested by experiments and shown to be correct.
Professor White added:
“We are particularly proud of our combination of maths and experimentation. This is due to the strong support from BBSRC for the area of systems biology and the work of a dedicated team of scientists from different disciplines.”
The paper, Dynamic NF-κB and E2 interactions control the priority and timing of inflammatory signalling and cell proliferation is available. It is available on the eLife website
A major part of the Semester 2 Biology tutorials involves a group project where our first year students work together on a project that brings biological science to the local community. This allows the students to engage actively in science-based activities within the local community while developing team-working, project-management and problem-solving skills. On May 9, 2016, a symposium was held where each first year biology tutorial group presented their projects to each other and to an elite panel of Faculty of Life Sciences judges – Professor Matthew Cobb (Professor of Zoology), Professor Cathy McCrohan (Professor of Comparative Neurobiology), Professor Liz Sheffield (Associate Dean for Teaching and Learning) and Mr Rory Beresford (Final year Biology Student Representative on the Student-Staff Liaison Committee).
More than 75 students took part in the 2 hour event which highlighted the scope, diligence and imagination involved in bringing biology to the local community. Students worked as tutorial groups to raise funds and awareness through cake sales, informative leaflets, and by setting up information stands in the Stopford, the Student Union and at events like Just Fest 2016. Through these activities they supported diverse topics such as Manchester’s bees, Food Waste, Blood Donation, and the Christie’s hospital. Others laboured to improve the environment by clearing allotments, planting pumpkin patches and building composters with local/University organizations like Hulme Garden Centre. Others work on upland restoration by planting sphagnum moss. Groups also worked to raise awareness about the benefits or organic farming and the lack of composting on the University campus.
The overall winner of the day was a group of students from our Associate Dean for Social Responsibility, Prof Amanda Bamford’s tutorial group who raised awareness of the thermoregulatory issues neonates face (see photo). Their campaign, ‘knit for neonates’ reached out to the wider community and encouraged people to knit hats to cover the heads of these tiny babies to prevent heat loss. By engaging retired members of the public (who arguably had the best knitting skills) , they also helped reduce the social isolation felt by many seniors. Together, with the help of Stopford Reception staff and other knitters, they collected 917 knitted caps for St Mary’s hospital! They plan to continue the initiative and encourage their world-wide team of knitters to make blankets as well as little hats. Members of this winning team were each presented with an award (High Street Gift Certificates worth £20) by Professor Liz Sheffield.
An honourable mention went to Dr Ron Burke’s tutorial group who decided to tackle the disengagement many youngsters have for science. They researched schools and curriculums and then developed an engaging and informative series of activities to enthuse students in Science. They spent a day during National Science Week in a local school with students in the final year of primary. Their aim was to make pupils consider science as a subject and also as a career when they moved schools next year. Upon presenting the awards Professor Liz Sheffield remarked that “it was fantastic to see the resourceful and imaginative ways our students brought science to the community. Many of the projects will have a lasting legacy”. The event was rounded off with a pizza party for the students, Advisors and Judges who deserved both praise and pizza for their hard work!
Photo of the judges and the winning group ‘Knit for Neonate’. From Left to Right: Cathy McCrohan, Rory Beresford, Matthew Cobb, back row: Cam Brough, Rowena Seaton Kelly, Kira Pattinson, Kath Bailey; front row: Jenny Capel, Lucy Helas, Amanda Bamford, Ffion Hall, Rachel Sparrow, Ben Williams and Liz Sheffield.
Article by Biology Programme Director Holly Shiels
The academic year 2015-16 is drawing closer to an end, and it’s been another great year for the Faculty. We thought it would be nice to have a reminder of some the research that has come out of the Faculty this year so far. After all, what better year is there to do it than 2016? – When Manchester is named European City of Science. From all the positive research outcomes of the Faculty this year, it’s certain that this has helped Manchester live up to this name!
2016 started off with a paper published by FLS scientists which showed that there are genetic variants in offspring that can affect the quality of maternal behaviour. The trials for this study consisted of mice families with genetically variable mothers and genetically uniform offspring, and vice versa.
Dr Reinmar Hager, the senior author on the paper, told us how this research is…
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This week we are featuring Dr Andrew Almond who was recently nominated for the BBSRC innovator of the year award. Find out why by reading this Tuesday Feature.
Please explain your research to the general public in about ten sentences or less.
Our research is focussed on understanding the biological function of sugars. Sugars are a major calorific component of food but can also be fibrous structural materials that hold cells together. In plants the major structural material is cellulose, which binds cells and gives physical strength. In humans more complex proteoglycans, which are present between every cell throughout the body, are the basis of a similarly-functioning glue-like material. This glue, or extracellular matrix, can have many forms and functions, such as rigid bone, shock absorbing cartilage, elastic heart valves and the complex structure of the brain. Proteoglycans are rich in large sugar polymers, which absorb water and salts, allowing our bodies to maintain their physical condition and hydration.
We have pioneered research aimed at resolving the microscopic configuration of the sugar polymers from proteoglycans, in order to understand their function and to aid development of synthetic biocompatible materials. This has involved detailed computational modelling and state-of-the-art experimental techniques to test the computer models. Due to the complexity of the sugars polymers and their close interaction with water, we have had to employ very fast computers and novel algorithms to study them; we pioneered the application of ultra-parallel graphics processing units (GPUs) to this problem (initially invented to meet the very intensive processing required for realistic action in video games).
How does your research benefit the general public?
Our basic scientific research is aiding development of novel biocompatible materials that can be used in transplants, prostheses and medical devices. The new discoveries that we are making could also pave the way for new treatments for Alzheimer’s disease, cardiovascular disease and cancer. Another aspect of our research is the technology that we develop. One piece of technology, directed toward accurately measuring the microscopic shape of drugs, was spun out of The University of Manchester into the start up company C4XDiscovery.
C4XDiscovery is focused on optimising the design and development of medicines and partnering with the pharmaceutical sector to generate better, safer products. C4XDiscovery was listed on the London Stock Exchange in 2014, valuing the Company at £31m. The Company is located in central Manchester and has over 20 highly-qualified employees. It is applying its technology to discover new drugs to treat addiction, diabetes and chronic inflammation and taking them through to clinical trials in partnership with the pharmaceutical sector. The Company is a significant new addition to the UK bio-economy, particularly within the North of England, and will ultimately benefit patients.
How did you first become interested in your research?
Although my undergraduate degree was in physics I had the ‘mis’-fortune of living with medical students. This led to many interesting discussions and an appreciation that biology is perhaps more poorly understood than other sciences at a reductive level. Furthermore, while mathematics and physics has already had a major impact on biology, for example, x-ray crystallography of DNA and proteins, it appears clear that they will have an increasingly important role to play. Multidisciplinary science is in my opinion the only way that we will really get to grips with biology, which appears to be vastly more complex than atoms and galaxies.
Did you have any science heroes growing up? Who inspired you?
When I was younger, probably like most people, I was mainly inspired by TV presenters. I was fascinated by nature and astronomy and used to watch and marvel at documentaries by David Attenborough and Patrick Moore. As I got older, and had access to science books and magazines, I became interested in the work of Linus Pauling and Richard Feynman.
How has working in Manchester helped you?
Since the nineties, when I was a PhD student at the old Victoria University, the growth and improvement in research and teaching facilities in Manchester has been huge, including many new state-of-the-art buildings. Furthermore, the University has one of the, if not the, most supportive and reasonable technology transfer offices in the UK. These environmental factors have been a tangible aid to spinning out a company and performing the world-class research that underpinned it.
What do you do outside of work?
Long distance running and equity trading, when I get a chance!
Hundreds of thousands of people worldwide, who have a disease that can lead to blindness, could have their sight restored after The University of Manchester entered into a technology license with Seattle-based company Acucela Inc.
The agreement will see Acucela commercialise technology developed by researchers at The University of Manchester that has the potential to partially restore vision in people who are blind from degenerative retinal conditions such as Retinitis Pigmentosa (RP).
RP is an inherited retinal disease that causes a progressive degeneration of the photoreceptor cells in the eye. Often beginning in childhood, RP patients most commonly first experience difficulties with peripheral and night vision, followed by poor colour perception and central vision; in many sufferers this can eventually result in legal blindness. RP affects approximately 1 out of every 4,000 people in the US, Europe and Asia, around 1.5M people in total, and there is currently no effective treatment for this disorder.
Acucela, a clinical-stage ophthalmology company that specialises in developing treatments to slow the progression of sight-threatening diseases of the eye, will now undertake a programme of clinical trials ahead of commercialisation of the technology. It is anticipated that the first patients will be treated within 3 years and Acucela plans to evaluate the ability of the therapy to partially restore vision in patients who are legally blind.
The therapy was developed by University of Manchester researchers Dr. Jasmina Cehajic-Kapetanovic and Professors Robert Lucas and Paul Bishop. In advanced RP the photoreceptor (light-sensitive) cells die off, but other neuronal cells are still present in the retina. In trials using RP affected mice with a complete loss of their photoreceptor cells, the scientists used a gene therapy approach which successfully made these other cells light-responsive. This optogenetic therapy was sufficiently effective at restoring visional responses in the mice to allow them to detect spatial patterns presented using an ordinary flat screen display.
Dr. Ryo Kubota, Chairman, President and CEO of Acucela said:
“We are extremely excited to enter into this collaboration with the University and to begin the important development work needed to unlock the potential of optogenetic gene therapy to improve visual function in patients who have lost much of their vision as well as their hope.”
Dr. Paul Bishop, FRCOphth, PhD, Professor of Ophthalmology, University of Manchester added:
“This is a very exciting therapeutic approach as the blind mice we treated could see surprisingly well in normal lighting conditions, and we think the approach may be safe as we are putting a normal human retinal protein back into the retina, but in cells that don’t normally make it. We are delighted at the prospect of working with Acucela towards restoring some visual function in patients who have severe visual loss from RP and similar conditions.”
Director of Operations at UMIP, Dr. Rich Ferrie commented,
“We believe that Acucela is the ideal partner to develop a gene therapy for RP based on this ground-breaking science. The licensing arrangement has the potential to deliver significant economic return to the University if the clinical trials and commercialisation programme are successful. More importantly the signing of this agreement represents a potentially pivotal moment and offers real hope for millions of RP patients around the world.”
The technology was first reported in Current Biology in June 2015 and in The New Scientist in August 2015 and it was also presented at the ARVO eye research conference in the US in May 2015.
Two University of Manchester scientists have been shortlisted for the prestigious BBSRC Innovator of the Year award. Both Dr Sheena Cruickshank and Dr Andrew Almond from the Faculty of Life Sciences have been nominated.
The BBSRC Innovator of the Year will be awarded on the 18 May at the Fostering Innovation event in London. The award recognises scientists who have been able to harness the full potential of their research leading to breakthroughs in their respective fields. An award nomination is a recognition of a scientist’s excellent work and effort.
Dr Andrew Almond received his nomination in helping to pioneer the C4X venture. C4X is a spin-out company that uses a new approach for for 3D modelling of specific structures with high accuracy. This modelling has helped to develop new and effective drug targets and does so in a much more efficient way; sometimes saving up to 90% of the normal production costs. The company is now estimated to be worth £31 million.
On receiving the nomination, Dr Almond said:
“I was delighted to receive the news that I had been shortlisted for BBSRC Innovator of the Year and surprised by the very positive feedback from the review panel. C4X Discovery, now listed on the London Stock Exchange, is building the world’s most productive drug discovery engine and its recent ground breaking R&D in the areas of addiction, COPD, inflammation and diabetes are poised to deliver substantial patient benefits. It is testament to the University of Manchester’s world leading research environment and its assiduous support for innovation and commercialisation.”
Dr Sheena Cruickshank has received her nomination on the basis of her work, in raising awareness and involving the public in her research around infection and immunology, in both local and global communities. Sheena studies neglected tropical diseases and her work with international populations of people now based in the UK has directed and informed her research which now focuses on ways to better diagnose and monitor infection. Her work identified a need to develop science resources that would remove barriers to accessing healthcare, enabling dialogue and discussion. These resources have been used in Bolton College and more recently in Madagascar. In addition in response to concerns from international communities about allergies she worked with the public, teams of scientists and the Royal Society of Biology and British Society for Immunology to create the #BritainBreathing app which uses citizen science to further research into seasonal allergies.
On receiving the nomination, Dr Cruickshank said:
“I was thrilled to receive the news that I had been shortlisted as I am passionate about sharing my research with the public and believe this is a vital part of a scientist’s role in society. Working with the public has been vital to my research and really driven its direction and shaped its content. Hearing people’s own reflections on infections and the barriers to healthcare is deeply moving and I have been privileged to work these people as well as my amazing collaborators who have enabled this work. This project is one of many that reflect the University’s commitment to Social Responsibility.”
As World Autism Awareness Week goes into full swing Dr Emma Gowen, a University of Manchester expert in the condition explains what more needs to be done to make autistic people’s lives better.
“As a researcher, I’m struck by how much more we talk about autism nowadays – but also by how many misconceptions still predominate. World Autism Awareness Week is a fantastic opportunity to talk about these issues and that’s been helped no end by the excellent drama on BBC 1, the A Word. Our project at Manchester, also aims to make an important contribution.
“The A Word does seem to reflect the difficulties that parents face after diagnosis, as support is so patchy and often poor: they are often left in limbo – with little or no support over decisions such as whether to be home schooled or not, and are often spoken to in professional terms that mean little to ordinary working people.
“Our project runs in partnership with Salfordautism, a local peer-support and advocacy organisation. During three workshops, we met many people who live with autism to discuss how academics and autistic people might work together to learn more about autism, resulting in a series of honest and revealing short films The films highlight misconceptions autistic people face – as well pointing us researchers to those areas which are important to autistic people themselves.
“Many people think that autistic people have extraordinary talents, but in fact, only at most 1 or 2 in 200 individuals can be described like that. Everyone has their own strengths and weaknesses, and that includes all autistic people.
“And while many people think the condition just affects children, it is simply not true: less than 25% of all autistic people are children and all autistic children grow up to be autistic adults. While over 75% of autistic adults are capable of and wish to work, only 15% are in full-time paid employment. And at least one in three autistic adults experience severe mental health difficulties due to a lack of support.
“And yes, women can be and are autistic, too. Officially, five times as many men than women are diagnosed with autism but research shows that autism spectrum disorders are vastly under-diagnosed in women, so the balance between the sexes may be much closer than that.
“Societies awareness of autism has increased, so that’s a good thing. Sadly, this can lead to the misleading impression that it’s on the increase when there’s no indication that it is any more or less common now than at any time in the past. What we are seeing is actually a result of changes in how diagnosis was carried out up to the 1980s – when autism was defined very rigidly and perhaps inappropriately. The definition has now been much improved by greater awareness of newer discoveries.
“There is also a growing understanding of the inappropriateness of the ‘medical model’ of autism, which tends to look for a cure, and uptake of the ‘social model’ which seeks to understand and accept everyone’s individuality: many healthcare professionals and most autistic people now seek to create a supportive environment in which autistic people can flourish. And that, most of all, is what I hope this week will get across.”
A University of Manchester team is to develop a new vaccine against the Zika virus as part of a new initiative to counter the disease which has spread rapidly across the Americas in the last few months.
The team will create and test a vaccine based on a safe derivative of a pre-existing smallpox vaccine – the only disease to have been successfully globally eradicated.
Dr Tom Blanchard, Honorary Senior Lecturer at The University of Manchester and Fellow of the Liverpool School of Tropical Medicine and Consultant in Infectious Diseases at North Manchester General Hospital and the Royal Liverpool Hospital will lead the project. Professor Pam Vallely and Dr Eddie McKenzieare University of Manchester experts involved in the project and the work will be done in collaboration with Professors Miles Carrol and Roger Hewson from Public Health England.
Dr Blanchard said:
“As we have seen in the case of Ebola there is now a real need to react quickly to fast spreading tropical diseases. Zika can cause serious illness, but it often has no visible symptoms, so a vaccine for those at risk is one of the most effective ways we have of combatting it.”
Zika virus was first identified in Uganda in 1947 and the disease is mainly spread by mosquitoes, though there have been reports of human to human transmission. It is particularly serious for pregnant women, as it’s been linked to birth defects – in particular, microcephaly, a condition where a baby’s brain doesn’t grow properly and it is born with an abnormally small head and serious development problems.
A recent and particularly severe outbreak which began in South America and has since spread north to United States Territories prompted the Medical Research Council, The Wellcome Trust and the Newton Fund to launch a £4m rapid response funding initiative at the beginning of February.
The results of this call for proposals have been announced today and Dr Blanchard and his team were awarded £177,713 to build and test a vaccine as part of this.
It is expected that the results will be delivered within 18 months and although the first target will be the Zika virus, the nature of the vaccine candidate may enable it to combat many infectious diseases simultaneously.
Dr Blanchard added:
“We know that there’s an urgent need for this vaccine but we’ll be working carefully to deliver a product which is safe and effective and which can be quickly deployed to those who need it.
If we can also use this vaccine on multiple targets then this will represent an exciting step forward in dealing with these kinds of outbreaks.”
Faculty scientists have made an important discovery in skin cancer treatments. They found that the HIV drug Nelfinavir can help treatments of melanoma to become more potent.
Skin cancer is a major problem in the UK, with more than 13,000 people being diagnosed with melanomas every year and over 2,000 people dying from it. There are drugs that are available to help treat melanoma skin cancer, but these can be ineffective because melanoma cells become resistant to them over time. After the resistance, the cells go on to make genetic changes which make it extremely hard to attack them.
Professor Claudia Wellbrock and her team found that Nelfinavir can help prevent cancer cells from becoming resistant to the treatment, making the cancer fighting agents more effective for a longer time.
The team discovered that cancer cells were able to rewire themselves by using a molecular change. This change that typically takes place in the first two weeks of cancer treatments, helps the cancer cells to develop resistance.
It was this molecular change that Wellbrock targeted by the use of Nelfinavir. It was found that Nelfinavir actually blocks the cells from rewiring and they were therefore less likely to develop resistance to the cancer treatment.
It is now thought that Nelfinavir could be administrated alongside existing cancer drugs in order to improve their effectiveness and boost the patient’s chances of survival.
Professor Wellbrock says:
“In the first few weeks of standard treatment for skin cancer, the cancer cells become stronger and more robust against treatment. But if we can target skin cancer cells before they become fully resistant, we would have a much better chance of blocking their escape. We think this research has brought us one step closer to making this a reality.”
The paper can be found at Cancer Cell http://www.cell.com/cancer-cell/fulltext/S1535-6108(16)30037-X
This week we’re featuring Dr Holly Shiels – a senior lecturer in cardiac physiology. Without any further introduction, let’s get right into it.
Please explain your research for the general public in around 10 sentences or less
Survival of nearly all vertebrate animals depends on maintained cardiac function. Environmental changes, such as temperature and oxygen fluctuations, can dramatically affect the ability of the heart to maintain normal function. To this end, we explore strategies of cardiac adaptation that permit maintenance of heart function in ectotherms living in fluctuating environments. We try to understand this across levels of biological organisation and in a range of species including tuna, trout, turtle, caiman, zebrafish, catfish, varanid lizard, rat and hamster and even human!
What benefit does your research give to the people reading this blog?
Recently we have been working on the effect of oil spill pollutants on the hearts of fish. This is important for understanding the implications of environmental disasters on aquatic species. Fish have a number of uses for humans – from food, sport and hobbies to thriving ecosystems which help sustain the environment here on Earth.
How did you first become interested in your research area?
During my PhD I had my first chance to work on large pelagic fish like tuna and swordfish. These animals move through thermoclines and hypoxic zones in the ocean and their heart beats throughout. I found this fascinating and am still trying to understand how they do it today!
Did you have any science heroes growing up? Who inspired you to do science?
Growing up in Canada there was a TV program called ‘The Nature of Things’ it was hosted by an Environmental Science Professor at the University of British Columbia called David Suzuki. I liked it because it presented nature and the impact humans were having on it. This was a novel approach for nature documentaries in the 70s and it made me think that I had a responsibility to understand mechanisms of environmental adaption.
How has working here in Manchester helped you?
Manchester is a large institution with excellent facilities that attract world class scientists in nearly every discipline. This is a great benefit as it means the questions I can ask in my research are nearly endless; there will always be the equipment and know-how to address interesting questions.
What do you do outside of work?
I enjoy time with my family and friends.
A nationwide survey by ecologists has revealed that over 2 billion tons of carbon is stored deep under the UK’s grasslands, helping to curb climate change.
However, decades of intensive farming, involving heavy fertilizer use and excessive livestock grazing, have caused a serous decline in valuable soil carbon stocks in grasslands across the UK.
The nationwide survey was carried out by a team of scientists from the Universities of Manchester, Lancaster, Reading and Newcastle, as well as Rothamsted Research.
The team found that 60% of the UK’s total soil carbon stored in grasslands – covering a third of UK land surface – is between 30cm and 1m deep. The team estimated the total grassland soil carbon in Great Britain to be 2097 teragrams of carbon to a depth of 1m.
Though the effects of high intensity agriculture are strongest in the surface layer of soil, they also discovered that this deep carbon is sensitive to the way land has been farmed.
Dr Sue Ward, the lead author of the paper from Lancaster Environment Centre, said:
“What most surprised us was the depth at which we were still able to detect a change in soil carbon due to historic land management.
“We have long known that carbon is stored in surface soils and is sensitive to the way land is managed. But now we know that this too is true at considerable soil depths under our grasslands.
“This is of high relevance given the extent of land cover and the large stocks of carbon held in managed grasslands worldwide.”
In contrast, the soils that were richest in carbon were those that had been subjected to less intensive farming, receiving less fertilizer and with fewer grazing animals. The team found that soil carbon stocks were 10% higher at intermediate levels of management, compared to intensively managed grasslands.
Professor Richard Bardgett from The University of Manchester said:
“Our findings suggest that by managing our grasslands in a less intensive way, soil carbon storage could be important to our future global carbon targets, but will also bring benefits for biodiversity conservation.”
“These findings could impact how grasslands are managed for carbon storage and climate mitigation, as current understanding does not account for changes in soil carbon at these depths.
“Our findings suggest that by managing our grasslands in a less intensive way, soil carbon storage could be important to our future global carbon targets, but will also bring benefits for biodiversity conservation.”
The research is part of a five year research project, supported by DEFRA, aimed at managing UK grassland diversity for multiple ecosystem services, including carbon capture.
The paper, ‘Legacy effects of grassland management on soil 1 carbon to depth’ is available in the journal Global Change Biology.
New research has revealed the importance of a circadian body clock that matches the rotational speed of the Earth.
A team of scientists from Holland, Germany and the UK’s University of Manchester studied animals in which variation in a single gene dramatically speeds up the natural circadian cycle from 24 to 20 hours.
It is the first study to demonstrate of the value of having an internal body clock which beats in tune with the speed of the earth’s rotation.
The researchers released animals with 24 hour or 20 hour clocks into outdoor pens, with free access to food, and studied how the proportion of animals with fast clocks changed in the population over a period of 14 months.
This allowed the team to study the impact of clock-speed in context of the “real-world” rather than in captivity.
Mice with the 20-hour clock gradually become less common with successive generations, so that by the end of the study, the population was dominated by animals with “normal” 24h clocks.
This supports previous research which shows a connection between people who have abnormal body clocks because of things like night-shift work, and their chances of developing diseases like Type 2 diabetes.
But these studies now extend to the potential implications of space travel in the future. For instance, the Martian day is 37 minutes longer than that on earth.
Professor Andrew Loudon, from The University of Manchester said:
“The rotation speed of Mars may be within the limits of some people’s internal clock, but people with short running clocks, such as extreme morning types, are likely to face serious intractable long-term problems, and would perhaps be excluded from any plans NASA has to send humans to Mars.
If we ever do get to the Red Planet, I suspect we will be faced with body clock problems; those people with abnormally slow body clocks would be best suited to living there.”
“A correctly ticking body clock is essential for normal survival in the wild, and this has to be in phase with the rotation speed of the earth.
“Animals with clocks that do not run in synchrony with earth are selected against.
“Thus, the body clock has evolved as an essential survival component for life on earth.”
Professor Loudon is available for comment
A copy of the paper Natural selection against a circadian clock gene mutation in mice is available. It is published in Proceedings of the National Academy of Sciences
The interdisciplinary group, autism@manchester are looking to work with the autistic community to improve the effectiveness and impact of their research. Autism is a lifelong developmental condition that affects how the autistic person makes sense of and interacts with other people and the world around them, often causing them, and those affected by them, considerable difficulty, discomfort and anxiety.
autism@manchester involves autism researchers from the University of Manchester, Manchester Metropolitan University and the NHS, as well as autistic individuals and parents of autistic children. The group are concerned that the research they do should be relevant and of real advantage to those who live with the condition. At the same time, many of those affected by autism feel disconnected from the very research that is supposed to be helping them, and voice concerns that researchers are not working on issues that are important to them.
This is why researchers from autism@manchester are very keen to involve those who live with autism in the research process and were awarded Welcome Trust Institutional Strategic Support Funding to hold a series of three interactive workshops with members of the autistic community during November 2015. The project was run in partnership with Salfordautism, a local support group who work in the community to support autistic people and those around them. During the workshops, the autism@manchester team met with those who live with autism to discuss how best to work with the autism community in developing, choosing and designing research projects that would have real meaning for autistic people.
Emma Gowen, one the lead academics on the project, concludes:
“This was a highly challenging and exciting project to work on. One challenge was that the researchers involved were from a wide range of research disciplines – so we had to address communication barriers between the researchers as well as between researchers and the autism community. In the end, it all worked brilliantly! Everyone involved was very open and generous with their time and we learnt a lot from each other. It was a very enjoyable and encouraging interaction. However, this is only the beginning – we need to use the findings to develop some longer lasting initiatives”
Findings are currently being analysed and written up and will appear here when finished (http://www.autism.manchester.ac.uk/projectsandfindings/welcometrustworkshops/)
Episode 33 of the Tuesday Feature highlights Natalie: someone who is doing fantastic research and making a real difference for gender equality here in FLS.
Please explain your research to the general public in about ten sentences or less.
I work on diabetic neuropathy a disorder that can affect the nervous system in diabetes. It is associated with a die-back of the nerve endings that supply skin, muscles and internal organs. This can lead to a whole host of symptoms – from unpleasant gastrointestinal and bladder problems to increased skin sensitivity and pain, often even the pressure of clothes or bed sheets can cause discomfort. A loss of sensation can coincide with the die-back of the nerves, and this increases the chance of tissue damage and ulceration – which sadly often necessitates amputation of toes, feet or lower limbs. In my lab we are characterising key changes that occur in gene, protein and metabolite levels in the peripheral nervous system in diabetes. We are interested in finding out what causes the nerve problems and are looking for ways to promote regeneration of damaged nerves and protect nerve function.
A Minute lecture on diabetic neuropathy by Olly Freeman, see recent paper in Diabetes.
How does this research benefit the general public?
The World Health Organisation estimated that almost 1 in 10 adults worldwide have diabetes, and the incidence of diabetes is ever-increasing. Approximately half of all patients with diabetes will develop some form of diabetic neuropathy, from mild to more chronic. This can have a huge impact on health, happiness and quality of life. There is currently no treatment. Basic research is therefore needed to better understand diabetic neuropathy and ultimately develop an effective treatment that prevents or limits the progression of the disorder.
What are your other roles here in the Faculty?
I am currently the coordinator for the Women in Life Sciences (WiLS) group here in the faculty and also a member of the Equality and Diversity Leadership team and ATHENA SWAN self-assessment team. I first started going to the WiLS meetings when they were organised by Kathryn Else. At this time, I had just returned to work after my first maternity leave and started my RCUK fellowship, so I had a lot to learn – how to manage a lab, how to get lab work done in time for nursery pick-up time, and how to cope with very little sleep! I found the WiLS meeting really helpful – learning new management skills and strategies, making new contacts and friends and forging new research collaborations. Since taking over as coordinator I have organised several bespoke training programmes and workshops based on demand identified through suggestions and surveys (such as a 6-month Coaching and Leadership Program) and talks from internal/external speakers (such as Prof. Dame Athene Donald). I would particularly like to get more students and postdocs involved. Last year I worked with a number of very talented and enthusiastic undergraduates to arrange talks and create a great WiLS photoproject around the time of International Women’s Day. I am always looking for more ideas for workshop/meeting/International Women’s Day events– so if anyone has any suggestions please do email me.
How important is it for Women to be represented in life sciences?
Very! Life sciences does have a better gender balance than some other STEM areas, if you look at the profile of FLS from our ATHENA SWAN Silver renewal application you will see that women are generally well-represented (61% of our undergraduates, 50% of postgraduates and 51% of research staff are female). The proportions do decrease in academic positions and with seniority (32% of all academic staff in FLS are female; 17% of the professors are female), but there are signs that this gap is narrowing (for example, an increase in the proportion of female senior lecturers/readers over the last 5 year from 18% to 37%) hopefully this will continue.
Do you have any science heroes? who inspired you to do science?
Not sure I particularly have a hero – I was always interested in life sciences and was strongly encouraged by my teachers to study Biology at University. I caught the research bug during my final year project and decided to do a PhD. I greatly enjoyed the Royal Institutional Christmas lectures given by Nancy Rothwell, and this helped convince me to pursue a career in neuroscience. After some time doing postdoc positions in London, I moved to Manchester and Nancy became my mentor during my RCUK fellowship! I try to mention the work of Rita Levi-Montalcini in undergraduate lectures – a key woman in neuroscience! During World War II, her academic career was halted by Mussolini’s ‘Manifesto of Race’ so she responded by setting up a research lab in a bedroom in her parents’ house to study nerve development. She moved to a lab in the US in 1946 and six years later isolated Nerve Growth Factor – a factor which promotes nerve development, survival and regeneration. She shared the Nobel Prize in Physiology and Medicine for her role in this discovery.
How has working in Manchester helped you?
Manchester has a great research environment and people are willing to collaborate, so I have got to do work that I would not have been able to do elsewhere. The support facilities, and most importantly the people who run these facilities, are fantastic – a great source of advice.
Finally, what do you do outside of work?
I have two young sons which means that home life is loud and busy. We try and burn off energy at the weekends going walking, kicking/throwing/hitting balls around and recently by digging – as we have just taken on the challenge of an overgrown allotment.
- Pups don’t continue asking for more if they are already well provided
- Findings applicable to any social species, including humans
If a mother is already a generous provider, her offspring will nag her less, according to new research on mice by University of Manchester scientists.
The study, published in eLife, uncovers a fitness cost to begging for care, so pups don’t continue asking for more if they are already well provided. Pups that spend more time soliciting for care weigh less than those who are more easily satisfied.
Although the study was conducted on mice, the findings are applicable to any social species, including humans
Faculty evolutionary scientist Reinmar Hager says:
Our aim was to unpick the genetic conflict between the care a parent provides and the amount that offspring want,”
“If offspring are too demanding it can be costly to parents and to themselves. But if parents don’t invest enough, their genes may not survive the next generation,
The level of maternal care was measured as the sum of nursing, suckling and nest building behaviour. One of the most important roles of a mouse parent is to keep offspring warm. Hypothermia is the leading cause of death in pups.
A key part of the study looked at how genes expressed in offspring influence their mother’s behaviour. For the first time, the researchers were able to show that genes expressed in offspring affect maternal behaviour.
During their analysis, the researchers identified genetic variation in pups that influences nest-building by mothers. If a pup carries a specific variation of a gene on chromosome 7, from its sixth day of life its mother or adoptive mother will spend more time gathering nesting material and using it to construct and repair a nest.
Similarly, if a pup carries a specific variation on chromosome 5, from day 14 mothers show increased levels of maternal behaviour. This is a crucial time for pups as it is around the time when ‘weaning conflict’ is expected to be at its height – the battle between a developing pup’s desire to continue to nurse and a mother’s desire to stop is waged until pups are fully weaned at three weeks.
PhD Student David Ashbrook says:
“For the first time we have identified specific genetic variations in offspring that lead to preferential maternal treatment, which in turn improves offspring fitness,”
“There will therefore be a strong selection pressure on genes expressed in offspring that influence parental behaviour,”
However, all genotypes benefited from the extra investment by mothers genetically predisposed to give better quality care, known as the B6 maternal phenotype.
The paper ‘Genetic variation in offspring indirectly influences the quality of maternal behaviour in mice’ can be freely accessed online at http://dx.doi.org/10.7554/eLife.11814. Contents, including text, figures, and data, are free to re¬use under a CC BY 4.0 license
New research has revealed how the heart is one of the major factors which determine whether a fish lives or dies in oceanic Dead Zones.
Dr Holly Shiels, a Senior Lecturer in Animal Physiology at The University of Manchester, says the findings may explain why some fish are able to survive harsh environmental conditions better than others.
The research, published with Open Access in the journal Biology Letters, may help in the battle to understand why fish stocks dwindle in polluted marine environments with low oxygen levels – known as hypoxia.
Hypoxia, says Dr Shiels, is a growing problem in coastal environments, and is likely have enduring impacts on aquatic ecosystems and the fish that live within them.
There are over 400 so called “Dead Zones” worldwide, areas where aquatic life is limited or completely absent largely because there isn’t enough oxygen to support it
But by studying the European Sea Bass, an important commercial and ecological marine fish, the Manchester scientists, in collaboration with Guy Claireaux’s group at Ifremer in France, have identified a link between hypoxia-survival and the fish heart.
They think this link is important in understanding how fish tolerate harsh environments.
First the team revealed that hypoxia-tolerance is a stable trait – during repeated hypoxic-challenges over the 18 month study, certain fish in a population were consistently more tolerant of hypoxia compared with others.
They then went on to show that fish who tolerated hypoxia had hypoxia-tolerant hearts. This prompted Dr Shiels’ team to suggest that the heart and the cardiovascular system is a crucial survival factor.
Dr Shiels said:
“We were able to show that hypoxia tolerant hearts in fish correlates with a whole body effect. In other words, not only is the heart more resilient to hypoxia, but the fish as a whole is.”
Although fish don’t breathe as humans do with lungs and air, they still take in oxygen through their gills. So when oxygen in water is reduced, fish struggle to breath just as humans would on top of a mountain, where the air is thin.
Hypoxic Dead Zone can occur naturally, but their recent increase in size and distribution is often caused by human input of nutrients into the water, encouraging plant growth and algal blooms. The extra organic matter dies, sinks to the bottom and decays, creating hypoxic conditions.
Dr Shiels concludes:
“Our work is timely as hypoxia is a pervasive and rapidly growing problem in coastal environments world wide. Our study suggests the hypoxia-tolerance of the fish cardiovascular system may be key in determining fish distribution and survival in the changing oceans.”
The full paper, published today in Biology Letters, is available on request.
Faculty scientists have discovered a cluster of 60 proteins that allow the body’s cells to react to their environment and communicate with each other.
Professor Martin Humphries, who led the research team said:
Our findings on how cells sense their environment have unlocked an important key to understanding how we can persuade cells to form different tissues and how we might stop cell movement in diseases such as cancer.
Cells react differently to materials that are hard or soft, rigid or elastic. For example, stem cells on a hard surface develop into bone cells, while the same cells on a very soft surface make nerve cells.
Similarly, cells, including tumour cells, tend to move more rapidly on hard surfaces compared to soft surfaces. The ways in which cells sense this difference in their environment remains a mystery.
The research revolves around integrins -– a family of proteins that were discovered in the 1980s and are essential for cell growth and function.
Integrins, which are a building block of complex life, are found at the outer edge of cells and encourage proteins to assemble around them when they interact with the outside environment.
The team carried out complex experiments to understand the workings of the integrin protein clusters using mass spectrometry, and assembled a list of all the proteins in the system.
One member of the team, Dr Adam Byron, assembled similar data from across the world and distilled it into a list of 60 proteins that cluster around integrins.
Another member of the research team, Ed Horton, said:
After assimilating all the complex data which was available, we were surprised that only 60 proteins were the essential mediators of the information exchange between integrins and the outside world.
So there is now a consensus view: integrins work closely with at least 60 proteins to coordinate many functions including cancer cell migration.
And fellow researcher Dr Jon Humphries said:
Understanding how cells sense their environment is an important step in understanding how, for example, cancer cells move or how stem cells take on different jobs.
An electronic copy of the paper, Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly, is available on request.
This year a team of students went on a life changing trip to Madagascar to help educate and treat Schistosomiasis in the area. Here’s an account of their adventures.
What is Schistosomiasis and why did MADEX do this project?
Madagascar Medical Expedition 2015 was a student-led research expedition, which set out to screen school children for schistosomiasis in one of Madagascar’s most remote and isolated areas. We wanted to treat those with the disease and run health education programmes to teach the children ways of preventing re-infection.
Schistosomiasis is a parasitic disease caused by the Schistosoma fluke which is the second most important parasite-born disease after malaria. It is found in tropical, humid climates. People become infected through contact with water infested with the parasite larvae. There are three main species that infect people: Schistosoma haematobium which causes urinary schistosomiasis, and S. mansoni and S. japonicum which causes intestinal schistosomiasis.
The World Health Organisation (WHO) considers schistosomiasis to be the second most important parasite-born disease, second only to malaria in terms of global socio-economic impact. Approximately 166 million people are infected worldwide across 78 endemic countries and it is thought it causes around 20,000 to 200,000 deaths/year. The disease has a particularly serious impact on children as they become too ill to go to school. This impact on education has a major impact on the economy. For this reason the reduction of schistosomiasis is in line with the Millennium 2020 objectives for global health set out by the WHO. Control of schistosomiasis is based on treatment with Praziquantal (an anti-helminthic drug), improved sanitation and health education.
In Madagascar in 1987, approximately 16 million people were thought to be infected in a total population of 24 million. The WHO advises treatment via Mass Drug Administration every 6 months to any population which has greater than 50% prevalence; however in 2009 approximately just 20% of the population in Madagascar had received treatment.
Planning the expedition, and collaboration
This was the first ever student-led medical research expedition from The University of Manchester (UoM), and took over two years of planning. With the backing of The Ministry of Health Madagascar, we put together a proposal, and negotiated with Manchester Medical School to let us use the project for part of our university course. We organised training in microscopy and schistosomiasis identification with Professor Andrew MacDonald’s team and were supplied with brilliant education resources from Dr Sheena Cruickshank in the Manchester Immunology Group.
Four UoM students went to Madagascar: Stephen Spencer (Founder, Head and Lead Coordinator of the team), Anthony Howe (logistics and finances), Hannah Russell (medical, health and safety officer) and James Penney (research lead, and as a French speaker, in charge of international communications)
We also nurtured a collaborative link between UoM and The University of Antananarivo. We selected two recent medical graduates to join the field team: Daniel and Anjara. As well as being an extra pair of hands, they translated, took over the health education programme, and conducted interviews with local health workers, headteachers and village chiefs to investigate the health burden and health beliefs of the area, and so were absolutely crucial to the success of the expedition.
The research was based in the district of Marolambo, one of Madagascar’s most remote locations, situated in central East. We screened six schools from six villages in this district. This involved hiking between villages, sometimes up to 24km, through forested areas with nearly a quarter of a tonne of equipment.
We screened a total of 399 children from 6 schools, across 6 villages in the district. We looked for schistosomiasis by three different methods: 1) looking for eggs in stool samples 2) looking for eggs in urine samples and 3) using CCA antigen testing, to test for presence of the CCA antigen (given off by all schistosome species) in urine samples. In this way we tested for both urinary and intestinal schistosomiasis.
We found an overall prevalence of 94%, with our data showing that all of this was intestinal rather than urinary schistosomiasis. We also recorded extremely high egg counts, well over the WHO threshold for ‘intense’ infection, and on discussion of these results with experts, it is likely that if some of these eggs remain in the patient’s intestines then severe problems like liver cancer and splenomegaly could occur. Infection, if left untreated, can cause serious damage and even death, so it is critical to intervene with anti-parasite medicine and education. Further to this we ran health education programs to the school children, teaching them about schistosomiasis, how to avoid re-infection, and raising awareness to the local community.
What lies ahead for MADEX?
Our long-term goal is to control schistosomiasis in the Marolambo region.
We have met with the Ministry of Health of Madagascar in Antananarivo, who are keen for the work to continue. As well as ensuring complete treatment amongst this community, we would like to re-screen these populations to study the re-infection rates here. In addition to this, with follow-up projects, we also aim to reduce the disease burden by focussing on improving education about the disease.
We hope to make this a long-term project, and to continue the collaboration between The Universities of Manchester and Antananarivio, by sending out students year on year. Planning for an expedition in summer 2016 is underway.
Thanks to: Professor Anthony Freemont & Manchester Medical School, Dr Ed Wilkins & Infectious Diseases Unit (North Manchester General Hospital), Professor Andrew MacDonald, Dr Sheena Cruickshank & Manchester Immunology Group (University of Manchester), Dr Jane Wilson-Howarth, Anglo-Malagasy Society, Jayne Jones & Liverpool School of Tropical Medicine, Herizo Andrianandrasana & Durrell Wildlife Conservation Trust, Dr Peter Long (University of Oxford), Dr Shona Wilson (University of Cambridge), Schistosomiasis Control Initiative, Natural History Museum London, World Health Organization, Royal Geographical Society, East Lancashire Hospitals NHS Trust, Mission Aviation Fellowship, Dr Alain Rahetilahy & Madagascar Ministry of Health, Prof Luc Samison & University of Antananarivo, Dr Clara Fabienne & Institut Pasteur (Madagascar), Zochonis Enterprise Award, British Medical and Dental Schools’ Trust.
Rice – the staple food source of around 50% of the World’s population, has been domesticated on three separate occasions, according to a new study by Faculty scientists.
The work could be used to educate better rice grain improvement projects, something that may prove crucial with growing environmental concerns.
The study focused on three major types of rice: the long-grain Indica which is non-sticky and mainly found in tropical lowland Asia; Japonica a short-grain rice that produces sticky rice, like the one in sushi and Aus, the drought-tolerant variety that grows in Bangladesh.
Before this study, researchers had thought rice may have been domesticated once or perhaps twice. Scientists had looked at Japonica and Indica because they have had the longest history of cultivation. Some argue that Japonica came first around 10,000 years ago and that Indica emerged as a hybrid form of it a little later. Others contend that both Japonica and Indica have separate domestication events.
However, new analysis from Professor Terry Brown, Dr Peter Civan and colleagues add a third domestication event to the mix by showing evidence that Aus was also domesticated separately in a region from India to Bangladesh.
The team looked at genetic data from 446 samples of different wild rice to see how similar Aus is to Indica and Japonica. In most cases, Aus was not similar enough to be explained by a single domestication event. More specifically, they looked at ‘domestication sweeps’ which are specific parts of the genome that differ from wild types and that scientists believe were chosen by early farmers because they had a great advantage to growing more grain. For example, the sweep region includes the ability for rice plants to grow more vertically and so can be planted more densely.
Brown and the team say that the genetic evidence that they have collected shows that these advantageous genes were present in a number of wild type rice varieties that were widely distributed across South Asia. It is therefore possible for farmers from three separate locations to select these wild types with the ideal genes and begin to cultivate them.
But why the big deal about rice? Well rice is thought to have brought about the great civilisations in Asia and led the way for large-scale agriculture to take place. Rice acted as a reliable food source and so large numbers of humans could gather to form large villages and settlements. Understanding how rice was domesticated would allow scientists to get a better understanding of how civilisations grew and moved across Asia.
Professor Brown concludes:
Our conclusions are in accord with archaeological evidence that suggests widespread origins of rice cultivation. We therefore anticipate that our results will stimulate a more productive collaboration between genetic and archaeological studies of rice domestication.
Civáň, P., H. Craig, et al. (2015). “Three geographically separate domestications of Asian rice.” Nature Plants 1: 15164.
A revolutionary new approach developed by Faculty scientists has for the first time shown that epilepsy could be preventable.
Professor Richard Baines and Dr Carlo Giachello used a genetically-altered fruit fly to show that when nervous system activity is suppressed by shining yellow light through its embryo, it will not go on to develop symptoms of the disease when it gets older.
Though the procedure has only been used on flies, the team believe the Medical Research Council funded research proves that the development of Epilepsy can be stopped in its tracks if treated early enough.
However, the technique developed and tested over three-years and published in Current Biology, will not benefit individuals who already have epilepsy.
Professor Baines said:
“We’re excited by this discovery which we believe is proof of principle and a milestone in the way we understand epilepsy – though clearly more research is needed in mammals.
But if these findings are taken to their logical conclusion, then we might envisage the possibility of being able to treat individuals at an early enough stage so they do not go on to develop the symptoms of epilepsy.
After all, amazing though it might seem, the underlying biology of the central nervous system is the same in humans as it is in flies.”
People who suffer from genetic epilepsy, experience a period in the disease’s development called the epileptogenic process, the process which causes a brain to develop epilepsy.
Scientists have already discovered that starting treatment with antiepileptic drugs during the epileptogenic process will delay the inevitable onset of seizures.
However, this new procedure, which starts treatment during embryonic development and uses light rather than drugs to manipulate nervous system activity , seems to permanently prevent seizures altogether.
Flies do not have spontaneous seizures like humans – however according to the team, there is no reason to suggest that the effect would be any different.
The technique expresses a gene called halorhodopsin – an ‘optogenetic’ tool which allows yellow light to control cells in living tissue.
Dr Giachello added:
“By using this optogenetic tool, we found that if we prevent nervous system activity at a time when the fly embryo is between 80 and 90% fully developed, seizures stop entirely.
Optogenetics is a recent development in biology which is causing quite a bit of excitement, not just in the treatment of epilepsy but other illnesses too.”
Scientists have identified many genes that make humans predisposed to epilepsy. The identification of these genes makes it possible to screen for the disease before it starts and, as this new research shows, it might be possibly to intervene to prevent it.
Academics at The University of Manchester have dismissed the long-held argument that the ancient Egyptian queen Cleopatra was killed by a snake bite.
Andrew Gray, Curator of Herpetology at Manchester Museum, says venomous snakes in Egypt – Cobras or Vipers – would have been too large to get unseen into the queen’s palace.
He was speaking to Egyptologist Dr Joyce Tyldesley in a new video which is part of a new online course introducing ancient Egyptian history, using six items from the Museum’s collection.
According to Dr Tyldesley, the ancient accounts say a snake hid in a basket of figs brought in from the countryside, and was also used to kill one or two of her serving maids.
But according to Andrew Gray, Cobras are typically 5 to 6 feet long but can grow up to 8 feet – too big to hide very easily.
There would also be too little time to kill 2 or 3 people- because snake venom kills you slowly- with in any case only a 10 per cent chance of death.
Not only are Cobras too big, but there’s just a 10 per cent chance you would die from a snake bite: most bites are dry bites that don’t inject venom.
That’s not to say they aren’t dangerous: the venom causes necrosis and will certainly kill you, but quite slowly
so it would be impossible to use a snake to kill 2 or 3 people one after the other. Snakes use venom to protect themselves and for hunting – so they conserve their venom and use it in times of need.
Cleopatra is strongly associated with snakes, like many ancient Egyptian kings and queens of Egypt. In addition, Cleopatra also believed she was the embodiment of the Goddess Isis, who can take on the form of a snake.
Dr Tyldesley, who’s book Cleopatra: Egypt’s Last Queen was a BBC Radio 4 book of the week, says one aspect of the accounts has proved to be correct. The ancient Egyptians believed snakes were good mothers.
Very few snakes have a maternal instinct. However, the cobra is an exception: they sit on the nest and protect them until they hatch. So in this case, it seems the Egyptians were right.
The free Massive Open Online Course (MOOC), ‘A History of Ancient Egypt’, launches on 26 October.
Dr Tyldesley added:
The MOOC includes behind-the-scenes access at the Museum and detailed descriptions of many objects from our Egypt and Sudan collection.
Professor Andreas Prokop and colleague Sanjai Patel say the fruit fly – or Drosophila – can be used as a modern teaching tool to explain many biological concepts used in the school curriculum.
In a UK first, the scientists based at the University’s Manchester Fly Facility have launched droso4schools – a website with sample lessons and teaching resources for schools.
Professor Prokop said:
Fruit flies are a fantastic resource for schools as Drosophila is the conceptually best understood animal there is.
“It is used by over ten thousand scientists worldwide for cutting edge research, and it is easy to keep in schools for captivating, exciting experiments which bring life into the classroom.
According to the researchers, the flies are easy and cheap to breed; the equivalent of London’s population can be kept on a handful of laboratory trays.
The project website contains supporting documents and additional information to engage students who want to know more about Drosophila and help teachers who want to use flies in their lessons.
“Currently we have resources for teaching classical genetics, statistical analysis of experiments, concepts of nervous system function, the gene to protein concept, principles of enzyme function, genetic variation and Darwinian evolution. All with flies,” h
He has even created a computer game where flies develop from eggs and spawn against time and parasites. To play the game visit https://scratch.mit.edu/projects/74443210
To adapt resources to teachers’ needs, Prokop and Sanjai supervised two PhD students, funded by the Biotechnology and Biological Sciences Research Council, who worked as teaching assistants in two Manchester schools
The students then developed biology sample lessons in close collaboration with the teachers which can be downloaded from the droso4schools website
The lessons continue to be used in the two schools: Loretto college and Trinity Church of England High school
Professor Prokop added
Flies have all the ingredients to convey conceptual understanding of biology as well as the thrill and relevance of science as a subject and future career perspective.
Surita Lawes, Head of Faculty at Loreto Sixth Form College, who is also a biology teacher, said: “By studying mutations in Drosophila, our students have been exploring how alcohol and human culture affects our genetic make-up. It’s an excellent way for teachers to meet the challenge of revising many areas of the new linear syllabus using a topic designed to spark an interest.”
Tof Apampa, a student at Trinity Church of England High School said:
It was great having the PhD student working with us. We learnt about what we can study at university and how fruit flys can help scientists explain how the human body works.
Having the flies in the classroom was good fun. It was so clear to see how the old flies were less mobile then the young ones.
We then learnt how this can help us understand aging in humans. It also showed in a really clear way how using a large sample size is important when we are looking for patterns in scientific data.
If you want know how and why fruit flies became so important for biology research, Prokop and Patel have even created two very entertaining educational YouTube videos.
For more information visit http://www.flyfacility.ls.manchester.ac.uk/forthepublic/
To download the teaching packs and support information for teachers, visit the droso4schools website:https://droso4schools.wordpress.com
All school resources including computer game and YouTube videos are explained and summarised on this blog: https://poppi62.wordpress.com/2015/08/28/school-flies
Two Faculty scientists are helping to shape policy by submitting scientific evidence to the latest National Biodiversity Climate Change Report card. Ecologists Professor Richard Bardgett and Dr Franciska De Vries have both been asked to contribute to the report which summarises the latest scientific evidence and understanding of how climate change is affecting UK biodiversity. The card itself shows where observed changes are likely to have been caused by changes in the UK climate over recent decades, and assesses potential future impacts of climate change on biodiversity.
Dr De Vries says:
This report card is important because it shows, at a glance, how UK biodiversity is already being affected by climate change. It shows which ecosystems and groups of organisms are most vulnerable to future changes , and this information is important if we want to act on climate change and protect UK biodiversity.
It is important that we take action to protect UK biodiversity against the effects of future climate change, because many ecosystem services depend on the diversity and composition of communities present. The report card includes potential ways for adaptation to climate change. For example, it is now clear that the way we manage land influences how species populations and communities respond to climate change.
It is hoped that reports such as these will give governments a clearer picture on what actions should be taken to protect our environment.
A link to the report can be found here (pdf)
Scientists have discovered the cells driving the annual body clock in animals which adapts their body to the changing seasons.
The BBSRC team from The Universities of Manchester and Edinburgh reveal that cells in a structure called the ‘pars tuberalis’- which is situated in the pituitary gland – there are specialised cells that respond according how much daylight there is, providing an internal genetic calendar for the animal.
The activity of these “calendar cells” changes dramatically over the year, with different proteins produced in winter or summer months. The switching between proteins in calendar cells is what drives the seasonal cycle in sheep and other mammals.
The findings, published in the journal Current Biology, advance our understanding of how the environment affects animals – but could also be relevant to humans.
Lead Author Professor Andrew Loudon from The University of Manchester said: “Scientists have long puzzled over how many animals seem to change their physiology according to the seasons.
Animals need to change their physiology to predict the changing environment and increase their chances for survival.
For example, some animals hibernate through the winter and others, including sheep, will time mating to the winter so they can give birth in the spring – when more food is available.
Now we have a much stronger understanding about how the body’s so-called circannual clock regulates this process.
The study took three years to complete and involved analysis of how sheep respond to seasonal changes in daylength.
Dr Shona Wood, Research Associate from The University of Manchester said:
A similar structure can be found in most animals – including humans.
Scientists once believed that humans did not show seasonal adaptations, but more recent research has found that this may not be the case and in fact there is seasonal variation in protection against infectious disease.
Our study gives more increases our understanding of how this may work.
Professor Dave Burt from Edinburgh said:
The seasonal clock found in sheep is likely to be the same in all vertebrates, or at least, contains the same parts list. The next step is to understand how our cells record the passage of time .
Damla Kiral, a now third year MSci Zoology student, was awarded a Faculty Sustainability Studentship in Franciska de Vries’ lab to estimate the total amount of carbon stored in the Smith Quad. Soil is the third largest global carbon pool, and it stores more carbon than vegetation and atmosphere combined. The amount of carbon stored in soils can be increased to mitigate CO2 emissions, which cause global climate change.
Damla took soil samples from all vegetation types in the Quad and analysed them for total carbon content. She also measured the bulk density, soil depth, and area of all vegetation types, and calculated the total amount of carbon stored in the Smith Quad.
She found that the Smith Quad stores 12.1 tons of carbon in total. The majority of this carbon (75%) is stored in the grass areas, because grass covers the largest area of the quad. However, the raised beds had the highest carbon concentration (17%, compared to 7% under grass).
The total amount of carbon stored in the quad is equal to the amount of carbon emitted from 60 economy class direct return flights from Manchester to Paris.
This project illustrates the importance of urban soils in carbon storage, and the role the University can play in this. But, it also highlights an easier way for academics to mitigate carbon emissions, by simply cutting down their air travel.
In celebration of the Natural Environment Research Council’s (NERC) 50th anniversary, a series of special science outreach events have taken place as part of the “summer of science”. As part of this, four teams of scientists from the FLS were given funding to host the “FLS environmental roadshows”.
The roadshow took place in 3 events – the FLS Community Open Day, a special adult-only event at the Manchester Museum and a one day exhibition at the Jodrell Bank Observatory is Cheshire. The open day saw over 850 people come to the University where they got to learn about the exciting life of plants.
For the one day exhibition the team were based at the Jodrell Discover Centre. The family friendly event saw cockroaches running up children’s arms, earthworms moving through soil and hands on experiences with carnivorous plants. The adults at the centre were taught about food security, radioactive contamination and soil ecology.
Dr Giles Johnson, Deputy Associate Dean for Social Responsibility and Faculty Lead for Environmental Sustainability said:
For us, the event was a huge success. We were able to explain our science to a wide range of the public and we were also challenged to think about our science in new ways, by the questions we were asked. It was a great day out.
Becky Burns, the Head of Gardens and Interpretation at Jodrell Bank thanks the team:
Thanks to the FLS team for coming out to Jodrell Bank Discovery Centre with their Summer of Science Roadshow! Visitors of all ages enjoyed interacting with enthusiastic staff and students, exploring the world of plants and living creatures and learning about their ongoing research.
Jodrell Bank, famous for its radio telescopes, has a long lasting association with Life Sciences in Manchester. Even before the telescopes moved in, the Bank housed the Victoria University Botany department. The botany tradition has continued through to today with an extensive arboretum, which is where the national collection of apples trees bloom. It makes for a great visit – so why not treat yourself this weekend.
Human intelligence and knowledge depends on how we collect and use sharable resources, according to scientists from The University of Manchester.
Marco Smolla and Dr Susanne Shultz say in contrast with humans, the impact of competition means it is often costly for animals to learn from, or share information with others.
Using a computer simulation to mimic the behaviour of animals, the findings cast important new light on our understanding of human – and animal – behaviour.
The research is published in the Proceedings of the Royal Society B today.
Dr Shultz explains:
“Unique human traits include generosity, teaching and imitation. Our model suggests the key to both of these behaviours might lie in how we overcame the impact of competition, allowing us to share resources and information between us.
“It does not pay to share a blade of grass or a leaf from a tree. So animals that eat such foods do better by making their own decisions about what to eat rather than copying others.
“However, it does make sense to copy individuals using highly valuable foods even if the proceeds need to be shared.
“So, it is possible a key part of human evolution was learning to use sharable resource, for example by hunting large game.”
Until now, scientists have struggled to explain why animals chose not to learn from those around them when it seems a much easier and less risky way to get information than learning by yourself.
And the team realised that up to now, researchers had excluded competition from their models.
However, competition is one of the major mechanisms that shape interactions between individuals and groups.
Their computer program simulated individual animals that search, collect, and compete for food.
The food was spread over patches that could change over time.
But the crucial difference to earlier models was that individuals had to share food items if they foraged in the same place.
The simple addition resulted in animals ignoring others when using evenly spread out resources, but learning from others when using rare, highly profitable ones.
Marco Smolla said:
“What is surprising and previously unexplained is that non-human animals do not share or copy as much information as they might: this is almost as true for honey bees as it is for apes.
“But our study shows that competition for limited resources provides a compelling explanation.
“We found that when rewards are more evenly distributed in the environment or when our simulated patches quickly change the amount of food items, individuals are less likely to share or copy information.
“There is simply not much use in following others when an individual could also just find food on its own and then doesn’t have to compete with others.”
The paper ‘Competition for resources can explain patterns of social and individual learning in nature’ is available here: http://rspb.royalsocietypublishing.org/content/282/1815/20151405
Scientists at The University of Manchester have successfully restored the sight of laboratory mice suffering from a common cause of blindness in people.
A team led by Rob Lucas and Paul Bishop carried out the pioneering research which may help sufferers of retinitis pigmentosa, a group of inherited eye disorders.
The treatment works by expressing a light sensitive human protein called rod opsin into the undamaged cells of the retina, so that it will turn them into special cells called photoreceptors which enable sight.
It was trialled on mice who had inherited advanced retinal degeneration and so were blind.
The treated mice became able to distinguish not only light from dark but also flickering from steady light as well as spatial patterns and to detect a natural movie – an advance on attempts to combat the disorders using non-human proteins.
Retinitis Pigmentosa is a leading cause of blindness: 1.5 million people worldwide are thought to be currently affected.
Using a human protein, says another team member Dr Jasmina Cehajic-Keptanovic , minimises the risk of side effects.
Professor Lucas said: “We aim to find ways of restoring photosensitivity to the retina in conditions such as retinitis pigmentosa in which loss of rod and cone photoreceptors leads to blindness. The protein rod opsin restores some vision under normal office light conditions, allowing mice to detect images presented using standard computer screens. Other researchers have also had some success using other sorts of light protein, but these generally require much brighter light beyond what we generally experience.”
The team’s paper is to be published in the journal Current Biology on 17 August.
A team of scientists have carried out one of the biggest ever analyses of genomes on life of all forms. This has allowed them to map the evolutionary history of eukaryotic genes in unprecedented detail – giving insight into the mechanisms of evolution in the very earliest forms of life.
Their paper, which is to be published in Nature, builds upon the work of famous palaeontologist Stephen Jay Gould who suggested that even though evolution is usually a slow process, it can sometimes take great jumps forward in a relatively short space of time. This theory was called ‘punctuated equilibrium’.
The team, including Faculty scientist Professor James McInerney, wanted to look at the different ways in which eukaryotic and prokaryotic life evolved to see if there were any clues to how evolution could do these great leaps forward. Traditional models had shown that lateral gene transfer (LGT) (the flow and swapping of genes between two individuals) happened in prokaryotes and thus helped explain the enormous diversity they have compared to eukaryotes. The team therefore asked: could LGT in eukaryotes explain these great leaps forward?
The project lead, Professor Bill Martin of the University of Dusseldorf explains the results:
“The big surprise of the study was that eukaryotes, don’t engage in this kind of continuous gene swapping nearly as much [as prokaryotes] – though when they do, it’s a really, really important event and in early evolution, it corresponded to the origin of organelles. These events were huge evolutionary leaps”
Organelles are parts of the cell that scientists can use to help differentiate between eukaryotic and prokaryotic cells. Eukaryotes crucially have structures like mitochondria and chloroplasts, mini-factories that work in the cell to provide energy for the organism. Research has shown that both mitochondria and chloroplasts evolved from two cells coming together to share genes and form a ‘hybrid’ organism.
Importantly the team’s computer model has shown that after this initial hybrid-forming stage, the organism starts to lose some of its newly acquired genetic information. Professor McInerney explains:
“It’s like in a game of chess. The cells starts out with two full sets of genes, one from each symbiotic partner, all lined up at either end of the board. But during evolution, the pieces are removed from the board one by one, so that at the end of the game almost no pieces are left, and from those that are left one tries to reconstruct how the game went, retracing the moves back in time.”
The team’s research has therefore shown that these evolutionary great leaps forward can take place when prokaryotes and eukaryotes mix their genes together in an endosymbiotic event. This evidence gives strong support to the theory of punctuated evolution and can explain the origins of complex life here on Earth.
Historian of science and medicine Dr Duncan Wilson has been awarded a 5 year fellowship by the Wellcome Trust to fund research into considerations of human health in the history of animal conservation.
Dr Wilson, whose previous work examined the history of bioethics, will look at why scientists increasingly drew connections between species loss and human health from the 1940s onwards. He will focus on how this viewpoint led to ethical debates about which species we should prioritise in conservation programmes, which influenced and continues to influence the work of scientists working across universities, parks and zoos.
When asked about the project, Wilson describes:
‘A striking feature in coverage of epidemics like Ebola today are claims that increasing rates of species loss are, to quote the International Union for the Conservation of Nature “the leading driver of disease emergence in humans”. Scientists warn that species loss through hunting, habit loss and climate change causes viruses to “spill over” into humans and eradicates potential medicines.
These warnings link our health to the fate of endangered animals and raise difficult questions about which species we should preserve’.
‘Yet despite its importance for understandings of our relation to the natural world, we do not understand why this view of species loss emerged and became influential. My new project will show how scientists in the 1940s first drew on ecology to argue that extinction threatened human health. I will detail how these claims underpinned the work of conservation organisations, national parks and zoos, and will isolate the professional and ethical concerns that led scientists to prioritise certain approaches and animals.
‘Given the dire warnings about the rate and consequences of species loss today, with up to half of all plant and animal species predicted to become extinct by 2100, this project is vital for helping us reflect on the changing connections between human and animal health, and on why we value some animals over others’.
Faculty scientist, Professor Matthew Cobb has been shortlisted for the prestigious Royal Society Winton Prize.
In Life’s Greatest Secret: The Story of the Race to Crack the Genetic Code, Matthew talks about the fascinating history behind the genetic code and how scientists from the 1940s and 50s managed to crack it.
The Royal Society Winton Prize is the world’s leading science literature award and celebrates science books which are designed to be accessible for the general public. The book, released earlier this year, has received rave reviews:
“Authoritative… thrilling… a first-class read’ – the Observer
“A compelling fusion of science, history and biography” – The Sunday Times
“A masterly account… a delight” – the Guardian
On receiving the nomination, Matthew Cobb says:
“I’m delighted and honoured that Life’s Greatest Secret has made it onto the shortlist of this prestigious prize. I hope that it will inform and inspire readers, in particular school and university students.”
The winner will be crowned on the 24th September, with the winner receiving £25,000. The other five shortlisted authors will receive £2,500 each.
One of the most exciting recent developments in genetic technology is called CRISPR/Cas9: it allows scientists to precisely alter the genes of virtually any organism. This technique makes it possible to investigate diseases in new ways, by changing enzymes and other proteins and exploring the consequences. Scientists have now used CRISPR to produce a mouse in which a gene called PRCP, which is involved in a range of diseases, no longer functions.
PRCR is an enzyme that turns the hormone angiotensin II (Ang II) into angiotensin 1–7 (Ang 1–7), which in turn blocks Ang II. Increased Ang II activity is strongly associated with the onset of hypertension, atrial fibrillation and diabetic mellitus. Some patients with hypertension have a mutation in their PRCP gene; this mutation has now been imitated in the PRCP-CRISPR mouse. This animal model provides a unique tool that will enable scientists to understand how a single gene mutation can lead to multiple cardiovascular and metabolic diseases in humans.
Researchers at The University of Manchester carefully studied a network of proteins that kick into action when cancer cells in the lab are treated with a class of chemotherapy drugs called taxanes.
These drugs are commonly used to treat several cancers – including breast, ovarian and prostate cancers. But not all cancers respond to them, and it’s difficult to predict which patients will benefit.
The Cancer Research UK-funded scientists teased apart this network in a range of cancers to try and find out why some can survive taxane-based chemotherapy.
The team identified one particular component of this network – a protein called Bcl-xL – which helps the cancer cells survive treatment by blocking the self-destruct process that normally kills cells when treated with chemotherapy drugs.
By combining drugs to block Bcl-xL with taxanes, the researchers showed that the combination of treatments killed far more cancer cells in the lab than taxanes alone.
Study leader Professor Stephen Taylor, Cancer Research UK Senior Research Fellow and Leech Professor of Pharmacology at The University of Manchester, said:
“This important research shows us there’s potential to boost the cancer-fighting power of chemotherapy – and do more with less.
This new combination could ‘soften-up’ cancer cells, making it easier for chemotherapy to deliver the final blow and destroy the tumour. And the good news is that drugs targeting Bcl-xL are already out there and being tested in clinical trials.
Using this combination of drugs could improve treatment for patients receiving taxanes and lower their chemotherapy dose, which would also help to reduce side-effects.”
Dr Emma Smith, senior science information officer at Cancer Research UK, said:
“Predicting which patients will benefit most from different types of chemotherapy is essential if we’re going to make cancer treatments more effective and kinder.
In cases where patients don’t benefit from taxane-based chemotherapy, doctors could add drugs that target Bcl-xL to overcome cancer’s defences. It’s still early days for this research but, if the results are confirmed in clinical trials, it has the potential to improve treatment for thousands of cancer patients.”
Topham, C., et al, ‘MYC is a major determinant of mitotic cell fate’. Cancer Cell, 2015. DOI: 10.1016/j.ccell.2015.06.001
The sense of smell plays a decisive role in human societies, as it is linked to our taste for food, as well as our identification of pleasant and unpleasant substances. A group of scientists led by Dr Kara Hoover of the University of Alaska Fairbanks and including Professor Matthew Cobb of The University of Manchester, have studied how our sense of smell has evolved, and have even reconstructed how a long-extinct human relative would have been able to smell.
We have about 4 million smell cells in our noses, divided into about 400 different types. There is tremendous genetic variability within and between populations for our ability to detect odours. Each smell cell carries just one type of receptor or ‘lock’ on it – the smell floats through the air, fits into the ‘lock’ and then activates the cell.
Most receptors can detect more than one smell, but one receptor, called OR7D4, enables us to detect a very specific smell called androstenone, which is produced by pigs and is found in boar meat. People with different DNA sequences in the gene producing the OR7D4 receptor respond differently to this smell – some people find it foul, some sweet, and others cannot smell it at all. People’s responses to androstenone can be predicted by their OR7D4 DNA sequence, and vice versa.
The researchers studied the DNA that codes for OR7D4 from over 2200 people from 43 populations around the world, many of them from indigenous groups. They found that different populations tend to have different gene sequences and therefore differ in their ability to smell this compound. For example, they found that populations from Africa – where humans come from – tend to be able to smell it, while those from the northern hemisphere tend not to. This shows that when humans first evolved in Africa, they would have been able to detect this odour.
One possible explanation of the existence of the inability to smell androstenone is that it was involved in the domestication of pigs by our ancestors – androstenone makes pork from uncastrated boars taste unpleasant to people who can smell it. Pigs were initially domesticated in Asia, where genes leading to a reduced sensitivity to androstenone have a high frequency.
The group also studied the OR7D4 gene in the ancient DNA from two extinct human populations, Neanderthals and the Denisovans, whose remains were found at the same site in Siberia, but who lived tens of thousands of years apart. The group found that Neanderthal OR7D4 DNA was like our own – they would have been able to smell androstenone. The Denisovans are a mysterious group of our extinct relatives – we do not know what they looked like, and they are known from only one tooth and a finger bone, from different individuals. Their DNA showed a unique mutation, not seen in humans or Neanderthals, that changed the structure of the OR7D4 receptor.
Team-member Hiroaki Matsunami at Duke University in the USA reconstructed the Denisovan OR7D4 and studied how this tiny part of a long-extinct nose responded to androstenone. It turned out that despite the mutation, the Denisovan nose functioned like our own. Both of our close relatives, like our early human ancestors, would have been able to detect this strange smell.
This research shows how global studies of our genes can give insight into how our taste for different foods may have been influenced by variation in our ability to smell, and, excitingly, show that it is possible to see back into deep evolutionary time and reconstruct the sensory world of our distant ancestors.
Matthew talks about his research on BBC Radio 4. [>>14:19]
Hoover KC, Gokcumen O, Qureshy Z, Bruguera E, Savangsuksa A, Cobb M, Matsunami H. Global Survey of Variation in a Human Olfactory Receptor Gene Reveals Signatures of Non-Neutral Evolution. Chem Senses. 2015 Jun 13. pii: bjv030. [Epub ahead of print] PMID: 26072518
A cross-faculty team of scientists have made an important discovery that could aid the production of biofuels and produce important chemicals much more sustainably.
The team, based at the Manchester Institute of Biotechnology, is made up of scientists from the Faculty of Life Sciences and the Faculty of Engineering and Physical Sciences. They have identified the structure of two key enzymes that were isolated from yeast moulds. These enzymes play an important role in the production of hydrocarbons – long chains of organic compounds that make up plastics, lubricants and transport fuels.
Using existing biofuel technologies, it would be impossible to replace the current industrial demand for fossil fuels with ‘greener’ hydrocarbons. However, this research, published in Nature, provides a more environmentally-friendly, scalable alternative for the creation of biological hydrocarbons.
Professor David Leys, who led the research, investigated the mechanism that causes the common yeast mould to produce kerosene-like odours, right down to the atomic level. The smell occurs when the yeast mould is grown on food containing the preservative, sorbic acid. The team found that yeast uses a previously unknown form of vitamin b2 to help them make the volatile hydrocarbons that cause the kerosene-like smell. This same process was also discovered to help with the creation of vitamin Q10.
Professor Leys clarifies:
“Now that we understand how yeast and other microbes can produce very modest amounts of fuel-like compounds through this modified vitamin B2-dependent process, we are in a much better position to try to improve the yield and nature of the compounds produced.”
David Leys and his team didn’t stop there and have published side-by-side papers in the same Nature edition. In their second paper, the team looked at how alpha-olefins are produced. Alpha-olefins are a high value, industrially crucial intermediary class of hydrocarbons. They are used in the manufacture of flexible packaging and pipes, synthetic lubricants in oils and can be added to detergents to improve their strength. Better knowledge of these olefins could prove key in allowing us to become fossil fuel independent in the coming years.
Professor Leys concludes:
“This fundamental research builds on the MIB’s expertise in enzyme systems and provides the basis for the development of new applications in biofuel and commodity chemical production. The insights from this research offer the possibility of circumventing current industrial processes which are reliant on scarce natural resources.”
White, M. D. et al. “UbiX is a flavin prenyltransferase required for bacterial ubiquinone biosynthesis” will be published in Nature on Wednesday 17 June 2015. Advance Online Publication (AOP) on http://www.nature.com/nature
Paper doi: http://dx.doi.org/10.1038/nature14559
This manuscript explains how the vitamin B2 is modified and thereby recruited in bacterial vitamin Q biosynthesis.
Payne, K.A.P. et al. “New cofactor supports alfa-beta-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition” will be published in Nature on Wednesday 17 June 2015. Advance Online Publication (AOP) on http://www.nature.com/nature
Paper doi: http://www.dx.doi.org/10/.1038/nature14560
This manuscript establishes how the modified B2 is used to support the fuel-like compound production.
Collaboration between four UK universities has found that the world’s largest dinosaur isn’t quite as big as previously thought.
Faculty scientists from The University of Manchester teamed up with scientists from the University of Liverpool, Liverpool John Moores and Imperial College London to help create a computer reconstruction of a dinosaur called Dreadnoughtus. They used this model to help predict the overall mass of the now extinct animal.
Dreadnoughtus, a herbivore with a long neck and tail, was thought to weigh around 60 tonnes but this new model puts the dinosaur’s weight at a more moderate 38 tonnes.
The original estimate of 60 tonnes came from a calculation that was based on the circumference of one of the dinosaur’s fossilised remains and then comparing that to animals that are alive today and their weights. However, the team used a different approach. They fitted simple shapes to a digital model of the Dreadnoughtus’ skeleton and calculated the volume. This volume was then converted into a body mass, using data collected from similar modern animals.
Dr Charlotte Brassey who headed up the Faculty’s involvement explains the results:
“The model we have used here shows that for Dreadnoughtus to have reached the originally estimated size it would have either needed a much higher body density, or much more soft tissue than you find in living four-legged animals.”
“While Dreadnoughtus was clearly a huge animal, we don’t think it would have grown to quite as big as the 60 tons originally claimed. Estimating the size of an animal from its bones necessarily means you have to theorise, but we think our figure fits much better with what we currently understand about the size and shape of modern land animals.”
The paper, ‘Downsizing a giant: re-evaluating Dreadnoughtus body mass’, has been published in the Royal Society journal Biology Letters.
Almost £1.3 million has been awarded from Arthritis Research UK to scientists at the University of Manchester.
Faculty scientist Dr Qing-Jun Meng and his colleague, Dr Julie Gibbs from the Faculty of Medical and Human Sciences, have been awarded the fellowships (worth £845,918 and £434,767 respectively) in order to study the effects the body clock has on two common types of arthritis: osteoarthritis and rheumatoid arthritis. It is well known that the symptoms of arthritis fluctuate during the day and it is thought that this is linked to our internal body clocks.
Dr Meng is an expert in cartilage and joint damage linked to the 24 hour body clock of the human body. He’s now looking to use the fellowship to get a better understanding of how disruptions in the natural body clock could lead to an increased risk of developing osteoarthritis. He says:
“I am very pleased to receive this fantastic award, which will enable me to continue in this potentially very fruitful area of biomedical research. I believe this research will provide novel and medically relevant insights into one of the most common joint diseases that affect most elderly.”
Dr Gibbs’ research specialises in body clocks and inflammation. In particular, her research has shown that the body clock is a key regulator in inflammation. Arthritis is an inflammatory disease of the joints and so a better understanding of how the body clock helps to control inflammation may give us a greater insight into the role body clocks play in arthritis.
The duo are part of a larger team based here at The University of Manchester which collectively makes up one of the largest and most productive clock research communities in the world. Having successfully collaborated on previous projects, both researchers are looking to use their complementary research skills to tackle one of the biggest research problems in the arthritis field.
Professor Ian Roberts, Associate Dean for Research of the University’s Faculty of Life Sciences, said: “We are delighted by the two recent prestigious fellowship awards to these two excellent young researchers. They reflect the quality of research on body clocks ongoing in both faculties and offer a real opportunity to answer important questions on body clocks and human disease.”
Dr Stephen Simpson, Director of Research and Programmes at Arthritis Research UK commented: “…we’re hopeful that these two fellowships will take us closer to much-needed, more effective treatments for people with these painful, debilitating conditions.”
Faculty Scientists have made an important discovery about how cells change the strength of the connection between one another to match the various needs of the body.
The team, led by Dr Lydia Tabernero and Prof David Garrod, looked at desmosomes – structures that help to bind two cells together. Specifically, they looked at the desmosomes that are present between two cells in the heart and two cells in the skin.
Desmosomes are known to be specialised for their strong adhesion and this is what allows tissue cells to stick together despite the rigours of everyday life. However, under different situations, like embryonic development and wound healing, these connections would need to become ‘weaker’ in order to allow cells to move and grow. Until this point, scientists have been unable to determine how the desmosomes were able to change their adhesiveness.
The team found that the ‘adaptive strength’ of desmosomes is achieved by special proteins which protrude from the cell. These proteins are the ‘sticky’ points which connect two cells together. They found that the proteins were much more flexible than was previously thought, allowing cells to change the strength of the bond between one another.
To study the role of desmosomes, the team extracted these special proteins to see what they consisted of. They used a combination of different techniques which allowed them to build a computer model of the molecules that make the connections between the cells. They found that the molecules were much more ordered in stronger adhesions than in weaker ones. The molecules were able to change their level of organisation because of their flexibility.
Dr Tabernero comments:
“What is really fascinating about desmosomes is that they become weaker during wound healing and embryonic development, and this weakening is necessary to allow cells to move. In contrast, desmosomes are very strong in adult tissues, particularly in skin and heart. It has been incredibly difficult to work out how they do that but our findings shed new light on this.”
Professor David Garrod has studied desmosomes for decades. He says there are exciting implications for these findings:
“This is the first time that any structural information has been reported for desmosome adhesion. Understanding these cell junctions will be important for future biotechnology applications. We also hope our research will contribute to studies into wound healing, cancer and embryonic development.”
The paper “Cadherin flexibility provides a key difference between desmosomes and adherens junctions” was published in PNAS on April 28th 2015.
Faculty scientists have made a crucial discovery about an immune cell which is used in immunotherapies to treat diseases like type I diabetes.
Dr Mark Travis led a team from the Manchester Collaborative Centre for Inflammation Research who studied regulatory T-cells – important immune cells that prevent harmful immune responses. Their research concentrated on how these T-cells can help cure inflammatory diseases.
Generally, T-cells fight infections and are most useful when acting against foreign invaders in the body like pathogens. However, some T-cells react with our own tissues and cause damage – this is the basis for auto immune diseases like type I diabetes. This is where the regulatory T-cells come in. They help to fight against these rogue T-cells, preventing them causing damage to the body’s own tissue.
Regulatory T-cells are currently being used in clinical trials to help fight auto immune disease. The cells are taken from the patient, multiplied and then given back to them. This helps to suppress their illness.
The team have identified an important pathway by which the regulatory T-cells are activated to suppress the harmful T-cells during inflammation. Dr Travis explains:
“This knowledge is vitally important when trying to make regulatory T-cells for therapy. By knowing the importance of this pathway, we can now work to improve the suppressive nature of regulatory T-cells to make them more effective as treatments for disorders such as type I diabetes and organ transplant rejection.”
“It’s fascinating that getting rid of just one molecule can have such an impact on the body’s ability to fight disease. Our research is all about how the molecules interlink and react to each other, and in certain situations targeting just one molecule can boost or inhibit a response.”
The Faculty team demonstrated that the molecules are expressed in both humans and animals. The next step for them is to look at how the mechanism works in practice , using Inflammatory Bowel Disease as a model.
Faculty researchers have found that better method reporting in animal experiments could save hundreds of thousands of pounds as well as stop clinical trials that have no hope of success.
The team, led by Faculty member Dr Sheena Cruickshank and Professor Andy Brass of the School from Computer Sciences looked at 58 papers on research on inflammatory bowel disease that were published between 2000 and 2014. They found huge differences in how methods were reported and found that vital information about experiments were missing, meaning they couldn’t be accurately reproduced in animal or human models.
Dr Cruickshank says she was shocked at the lack of information provided in papers: “What our research has uncovered is that this lack of data makes it difficult to validate the experiment and the result. Crucially this is having an impact of the reproducibility of experiments, both in the animal model and when transferred to human trials.”
The team were originally investigating a bowel disease called colitis and were trying to generate a database of research articles. It became clear that the information reported in the papers was not sufficient as the data could not be understood by members of other disciplines. This poses a potentially huge problem as research is becoming increasingly cross-discipline meaning that multiple teams must be able to understand data from other fields.
In order to address the issue, the team has created a ‘critical checklist’ that lists what information should be included. The list includes nine keys areas, such as the gender of the research subject, as well as the environmental conditions they were kept in.
Dr Cruickshank explains: “Our checklist sounds like fairly basic information that should be in all papers. But over the past few years journals have asked for more and more abbreviated methods so information has stopped being included. Instead, papers are focussed on the results and discussion and sometimes you have to go back to a paper from the sixties to find the last time a particular method was accurately recorded.”
The team felt it was important to stress that poor reporting of methodology does not necessarily mean that the research is inaccurate. However, if the research is poorly documented, then it makes it much harder for other teams to reproduce the results and therefore can slow down the progression of further research.
Moving forward, the Manchester team is recommending that their checklist is adopted as a staple for all publications in order to improve the quality, comparability and standardisation of studies into inflammatory bowel disease. They believe it will make the interpretation and translation of data to human disease more reliable and ultimately contribute to making clinical trials more su
Faculty scientists have made a key finding that could help develop an early test for kidney disease.
Dr Rachel Lennon from the Wellcome Trust Centre for Cell-Matrix Research, led the investigation that looked at why some people are more susceptible to kidney disease than others. In particular, the study looked at why impaired kidney function is more common in Afro-Caribbean individuals and in males.
Dr Lennon and her team focused on the structure around the cells in the kidney, as this is where they believed crucial differences may lie. Kidneys contain numerous small filter cells which help to maintain the blood in a healthy, steady state. The filters are surrounded by a mesh of two different types of proteins which act like scaffolding, giving structure and protection. It is these two proteins that the team wanted to investigate.
To do this, they used mass spectrometry to analyse the kidney tissue from mice who had a variety of genetic backgrounds – some of which they knew were more susceptible to kidney disease.
The team found that there were significant differences in the compositions of the two kidney proteins between the mice. This difference was found to be greater between mice of different genetic backgrounds as opposed to gender.
After the analysis, the team then used an electron microscope to get a closer look at the two types of cells. The team found that the cells from the various mice had structural differences – showing that both the composition and the structure of the scaffolding around the kidney filters changed between mice.
Dr Lennon comments: “The most surprising thing about our findings were that the mice weren’t actually exhibiting any symptoms of kidney disease and were all still in full health despite having this different structure in their filters. Their kidneys appeared to be functioning normally.”
The team are now looking to use human tissue to investigate the reasons behind these differences and are hoping that they will be able to find a mechanism that could be switched off before symptoms of kidney disease become more apparent and damage occurs:
“What we’re hoping is that this research will help develop a test that picks up kidney disease or even just a susceptibility to kidney disease before any damage has been done. We’re also keen to look at whether we could manipulate the process which leads to the structural change to develop new, more effective treatments.”
View Rachel Lennon’s Minute Lecture on kidneys:
Faculty scientists now have a better understanding of how bodies react to allergies and parasites. The team, led by Professor Andrew MacDonald, have discovered a new way that immune cells control inflammation during worm infections and in allergic responses to diseases like asthma. The finding is important because inflammation can cause long-term damage and so understanding how it is controlled will help mitigate its effects. To do this, the team studied dendrites in both animal and lab models. Dendrites are specialised cells of the immune system that play a vital role in the initial response to both allergens and parasites. Their main function is to recognise infection and switch on channels to combat it – one of which is inflammation. How these channels were switched on by dendrites was previously unknown. What the team found was that a particular protein called Mbd2 plays a key role in allowing dendrites to produce an inflammatory response. When the proteins were removed, radically different cells were formed and these cells had a significantly impaired ability to switch on inflammation. It was also discovered that Mbd2 was an epigenetic regulator, meaning that it could modify the function of many different genes without altering their DNA structure. Professor MacDonald explains:
“For the first time we have identified that this protein is a key controller of dendritic cells during inflammation against parasitic worms or allergens. It’s an important step, as all inflammation is not identical, and scientists try to understand which specific cells and chemicals are more important in the body’s response to particular infections. In the past, medicines have had a broad approach, affecting all aspects of a condition rather than being targeted. In the future it might be possible to create medicines that control the inflammation caused specifically by an allergy or a parasitic worm, rather than by a virus such as a common cold.”
Professor MacDonald continues:
“With billions of people affected by both allergies and worm infections around the world it is vital that we develop better methods of treatment. It’s also important to tackle the inflammation caused by these conditions, as it has been shown to play a role in the development of longer term diseases such as asthma.”
Faculty researchers have revealed that the colour of light has a major impact on how our body clock measures the time of day.
It’s the first time the impact of colour has been tested. The research, published in PLOS Biology, demonstrates that the colour of light provides a more reliable way of telling the time than its brightness.
Faculty members, led by Dr Timothy Brown, looked at the change in light around dawn and dusk to analyse whether colour could be used to determine time of day. Their key discovery was that light was reliably bluer during twilight hours, compared to daytime.
The team recorded the electrical activity of the body clock of mice while they were shown different visual stimuli. They found that mice were much more sensitive to changes between blue and yellow in the colour of light, than to its brightness.
The scientists then created an artificial sky which imitated the daily changes in colour and brightness. Mice were placed underneath the synthetic sky for several days whilst their body temperatures were recorded.
Researchers found that the highest temperatures occurred just after night fell – when the sky had turned a darker blue, optimal for a nocturnal animal. When only the brightness was altered, the mice became active before dusk, demonstrating that their body clock wasn’t properly in sync with a normal day/night cycle.
The team concluded that colour must therefore play a role in the determination of the time of day.
On the importance of the research, Dr Brown says:
“This is the first time that we’ve been able to test the theory that colour affects the body clock in mammals. It has always been very hard to separate the change in colour to the change in brightness but using new experimental tools and a psychophysics approach we were successful.”
“The same findings can be applied to humans. So in theory colour could be used to manipulate our clock, which could be useful for shift workers or travellers wanting to minimise jet lag”
Faculty scientists have discovered a way to make trees grow bigger and faster. The research, published in Current Biology and funded by the BBSRC, has identified two genes which are involved in the growth process of poplar trees.
Professor Simon Turner, who led the research, says:
“The rate at which trees grow is determined by the rate of cell division in the stem. We have identified two genes that are able to drive cell division in the stem and so override the normal growth pattern”
The genes, called PXY and CLE, control tree trunk growth. When they were overexpressed, the trees grew twice as fast as normal – being wider, taller and producing more leaves. As well as increasing the biomass available for the growing biofuel and biotechnology industries, trees may be better prepared to handle the pressures of climate change. Professor Turner explains:
“Most plants, including crops, respond to adverse environmental conditions with lower growth rates that result in correspondingly lower yields. Understanding how the plants respond to environmental signals and to what extent we are able to manipulate them to override these signals is likely to be very important for continued improvements to crop performance. In future, it may be possible that manipulating the expression of the PXY and CLE genes can override environmental signals that normally alter plant growth.”
The team now plan to work with a forest products company to test their findings in the field. It is hoped that this research will be used to address the pressing challenge of keeping crop yields high in an increasingly harsh climate.
Faculty scientists have completed computer analysis of the deadly Ebola virus which has shown that it has not evolved to become any more deadly since its first outbreak almost 40 years ago.
The surprising results show that whilst the virus has undergone a high number of genetic changes, the virus has not become any more virulent. The findings, published in the journal Virology, help prove that the higher death toll in the current outbreak is not because of a change in the way the virus infects humans.
This may prove to be extremely useful. Professor David Robertson says:
“The fact that Ebola isn’t changing in a way that affects the virulence of the disease means that vaccines and treatments developed during this current outbreak have a very high chance of being effective against future outbreaks. It also means that methods to successfully tackle the virus should work again, so hopefully in the future an outbreak can be stopped from spreading at a much earlier stage.”
The team used a computational approach, developed by PhD student Abayomi Olabode, that was previously used to analyse changes in the HIV-1 virus. The major advantage of using a computer-based approach is that research can be carried out in a very quick and safe way – something that is vital when studying viral epidemics. Importantly, this type of modelling can be done in real time, meaning that scientists can better react to deadly diseases as they happen.
Viral outbreaks, such as Ebola, need to be continually monitored for any change, including those that make the virus less potent. If symptoms are less severe, there is a greater chance that the virus will go unidentified. Infected individuals can spread the virus more widely throughout a population, making it harder to trace those who have been exposed to it and ultimately causing more deaths. Professor Robertson comments:
“This level of surveillance will only become more essential in the fight against contagious illness as we live in an increasingly globally connected society.”
On the results of the study, Professor Tony Redmond, from the University’s Humanitarian and Conflict Response Institute says:
“These are very important findings and emphasise that the spread of the virus in this outbreak owed as much to factors within the human community than within the virus itself.”
It is now thought that computer approaches like this one used to study Ebola will become the standard way to look at viral epidemics in the future.