Zika virus vaccine to be developed in Manchester

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.”

 

Madagascar Medical Expedition 2015

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

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.

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Acknowledgements

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.

Tuesday Feature Episode 12: David Brough

On the back of Gloria’s glowing recommendation, we decided to track down David Brough who is a research fellow within the Faculty. In this episode you’ll get to find out about David’s research into inflammation and how Manchester has helped him as a young researcher.


Could you please explain your research, for the layman, in ten sentences or less?

David Brough holding the Love Life Sciences board.So I work on a process called inflammation which is our body’s response to danger. Unfortunately, sometimes during disease this inflammatory response makes the disease worse. I try to understand these processes to see if we can identify new ways to treat disease.

How does this research benefit the person reading the blog?

So my research is really basic and is at a fundamental level, but hopefully discoveries that I make will, in the future, translate to human benefit. The research I do, for the people reading this blog, will hopefully, in 10, 15, 20 years’ time will have informed some of the treatments or practices to treat inflammatory disease. Inflammatory disease encompasses very common, mainstream disease: Cardiovascular disease, inflammatory skin diseases such as ‎Psoriasis or brain diseases such as stroke or Alzheimer’s disease.

How did you first get interested in inflammation?

I was always very interested in science and biology and I was always interested in basic mechanisms in biology which could contribute to disease. It was during my PhD that I became interested in inflammation. Inflammation is a great area to work in – particularly the processes I work on because there’s so much biology we don’t understand and it is directly relevant to people of all ages because it’s a major contributor to disease processes. It’s easy to understand and justify the reasons for studying these inflammatory processes.

Do you have any science heroes? Who inspired you?

I was always very interested in stories of scientific discovery such as the discovery of DNA and Penicillin. My scientific heroes have always been scientists who have made great breakthroughs. However, there hasn’t really been any one particular person who I inspired to be.

How has working in Manchester helped you?
As a young researcher, Manchester has been a supportive environment and I have great colleagues in my department. They are people who have complimentary research interests and I have been able to work effectively and collaborate well. There have been a lot of opportunities to develop my career.

What do you do outside of work?

When I’m not working here, I have two children who keep me very busy. I do various sports – I’m involved in martial arts and I am a jujitsu instructor, which I do several times a week.


Thank you David for sharing a bit more about your research and your role in the Faculty! Come back next week for another exciting look at some of the people who are involved with the Faculty of Life Sciences.

New discovery provides potential boost for immune disease treatments

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.

Healthy T-CellGenerally, 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.”

He continues:

“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.

Structure may hold clues to help detect and combat kidney disease

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:

Tuesday Feature episode 5: Roberta Oliviera

We’ve spent a lot of time talking to researchers in the Tuesday Feature so far. It’s been fascinating. But, so far there’s been little Roberta in the labmention of those people in the background who make the research possible.

So today we chat with Roberta Oliviera, a Research Technician in the Manchester Immunology Group. She tells us a bit about her role, her inspirations, and how she got to where she is today.

Hi Roberta. Could you tell us a little bit about being a research technician? What does your day-to-day involve?

My role in the University is to provide support for other academics and students with their research.

Technicians sometimes run their own projects and report the results to the supervisor and at other times they can support to researchers running specific experiments or techniques. We also help with students and their projects.

I suppose we run the upkeep of the lab, the organisation, and the smaller functions like that.

What about the researchers you work with and the research you do? What is being studied?

Well, I work for Professor Richard Grencis in the Immunology Group in the Faculty of Life Sciences.

Professor Grencis is looking at the immune responses against the whipworm. He looks at the balance of the immune response in an individual and what dictates whether that individual is susceptible or resistant to infection.

When you look at parasitic infections and their responses, you learn a lot about the immune system. We can always apply those lessons to other things such as cancer, auto immune diseases, and allergies.

Roberta at workHow did you first get interested in science? Or in particular, this research area?

I did my undergraduate degree in pharmacy back in Brazil.

Working in the care industry in a developing country can be daunting so I wanted to do some work in the background and learn more about tropical diseases.

I did a bit of work with malaria and Chagas disease and then I moved onto pulmonary hypertension in cancer, and then I started working on parasites again with Professor Grencis.

 

Do you have any science heroes? Who inspired you?

Every woman in science is a bit of a hero  – especially the ones trying to raise a family alongside building their career. That’s a challenge I’m facing myself.

If I had to give a name I’d have to go with Marie Curie, obviously. She had a very strong work ethic and she was very generous with her work colleagues.

So I’d say Marie Curie.

Could you tell us a little bit about your interests outside of science?

I like reading. I like British and American authors and use it as an opportunity to learn a bit more about the Anglophone culture since I didn’t grow up in the UK.

But, because I have a baby son, I have to admit that currently my activities involve play dates and play groups.

How does being here in Manchester help with the work you’re involved in?

Working in Manchester is amazing. I think mainly the people – they’re very happy, friendly, and helpful.

I think The University of Manchester is ideally what you’d expect academia to be – everyone is very creative and very helpful. It’s a democratic environment to work in.

I think working at the Manchester Immunology Group is very nice because we have cutting edge research going on and amazing scientists in our group. Since I started working here, I have felt at home and made lots of friends, so what else I could ask for?

 

And what more we could we ask for from an interviewee? Thanks, Roberta. A fascinating insight from a slightly different perspective – invaluable information that’s made us want to talk to more ‘tekkies’ in the future.

But it’s another slightly different perspective next week as we chat to Associate Dean for Social Responsibility, Professor Amanda Bamford. Amanda has put research aside to focus on her new role and her teaching, so we’ll be finding out what helped her make that decision.

We hope you’ll join us!

 

Interview by Fran Slater and Kory Stout, Videos by Theo Jolliffe, Images by Nick Ogden

Worm Wagon – From Parasite Selfies to worms in a jar

On Friday 6th March, The University of Manchester hosted the ‘Worm Wagon’. The Worm Wagon, which started here at the Kory as a wormUniversity in 2009, has gone around the UK teaching the public about neglected tropical diseases. Specifically, the group looks at parasitic infections and how our bodies help fight against them. With over 25 different locations visited and with more than 5,000 people attending events, the Worm Wagon has proven to be a huge success.

The Worm Wagon workshop uses various different interactive elements to effectively communicate ideas about parasites. For example, the ‘parasite plunge’ is used to teach participants about how our body produces mucus which helps to purge the invaders from our bodies. The volunteer has to place their hands inside a mucus and parasite filled container (made up of rubber worms and jelly) and pick out a worm which they get to keep. This activity is coupled with some fascinating teaching resources which look at the lifecycles of worms such as Helminths and Tapeworms. Perhaps the most bizarre activity you can take part in is the ‘Parasite Selfie’. A cut out of a Whipworm, a type of Helminth which affects the large intestine in humans, is set up so that guests can be pictured as if they were the worm!

Visitors can also get up close and personal with worms by viewing specimens in jars.  From the tiny little Ascaridia Galli which is found in chickens, to the potentially enormous tapeworms that are found in millions of people, guests get to see exactly how these parasitic worms enter our bodies. This allows them to get a better idea of what the parasites look like and helps to educate them about preventative measures they can take to ensure they don’t become infected. This knowledge can then be tested in a fun game of Parasite Top Trumps! This specially designed game helps participants compare parasitic infections to other global diseases to help raise awareness of just how prevalent these conditions can be.

When asked about the importance of a better understanding of parasitic worms, Professor Kath Else, a Senior Research Fellow at the FLS and Worm Wagon coordinator had this to say: “They [parasitic diseases] have huge consequences because of the ill health – they trap whole countries into poverty because they have a knock-on effects on worker productivity and big effects on child development”

With parasite infections affecting well over a billion people worldwide, perhaps more people should come visit the worm wagon!

 

Guest blog by Kory Stout, Video by Matthew Spencer

Faculty scientists closer to treating osteoarthritis using stem cells

Repair of rat cartilage defect by human pluripotent stem cells-derived chondrocytes, courtesy of Aixin ChengFunded by Arthritis Research UK, Professor Sue Kimber and her Faculty team have developed a protocol to grow and transform embryonic stem cells into cartilage cells (also known as chrondrocytes). This could one day be used to treat osteoarthritis. Professor Kimber said:

“This work represents an important step forward in treating cartilage damage by using embryonic stem cells to form new tissue, although it’s still in its early experimental stages.”

During the study, the team analysed the ability of embryonic stems cells to become precursor cartilage cells. They were then implanted into cartilage defects in the knee joints of rats.

After four weeks, cartilage was partially repaired. Eight weeks after that a smooth surface resembling normal cartilage was observed. Further study showed that cells from the embryonic stem cells were still present and active within the tissue.
Despite the fact that this still needs to be tested on humans, researchers see this as an extremely promising outcome. Not only did this protocol generate new, healthy-looking cartilage but there were also no signs of any side-effects. Further work will hope to demonstrate that this could be a safe and effective treatment for people with joint damage. Prof Kimber added:

“We’ve shown that the protocol we’ve developed has strong potential for developing large numbers of chondrogenic cells appropriate for clinical use. These results thus mark an important step forward in supporting further development towards clinical translation.”

Osteoarthritis affects more than eight million people in the UK, and is a major cause of disability. It occurs when cartilage at the ends of bones wears away and it causes joint pain and stiffness. Dr Stephen Simpson, Director of Research at Arthritis Research UK, said:

“Current treatments of osteoarthritis are restricted to relieving painful symptoms, with no effective therapies to delay or reverse cartilage degeneration. Joint replacements are successful in older patients but not young people, or athletes who’ve suffered a sports injury. Embryonic stem cells offer an alternative source of cartilage cells to adult stem cells, and we’re excited about the immense potential of Professor Kimber’s work and the impact it could have for people with osteoarthritis.”

Computer model explains how the brain selects actions with rewarding outcomes

Brain modelFaculty research conducted in conjunction with The University of Sheffield has developed a computer model which charts what happens in the brain when an action leads to a reward. The model could provide insights into the mechanisms behind motor disorders such as Parkinson’s disease and conditions involving abnormal learning, such as addiction. Faculty researcher Dr Mark Humphries explains:

“We wanted to look at how we learn from feedback – particularly how we learn to associate actions to new unexpected outcomes. To do this we created a series of computational models to show how the firing of dopamine neurons caused by receiving reward ultimately translates into selecting the causative action more frequently in the future.”

Research had already shown that actions are represented in the brain’s outer layer of neural tissue (the cortex) and that rewards activate neurons that release dopamine. The dopamine signals are then sent to the striatum, which plays an important role in how we select which action to take. Together, this evidence suggested that dopamine signals change the strength of connections between cortical and striatal neurons, determining which action is appropriate in a specific circumstance. Until now, though, no model had tested these strands together. Dr Humphries explains why they created the model:

“Essentially, within this area of research, we are tackling a puzzle in which we have an unknown number of pieces and no picture to guide us. Some pieces have been studied individually, so the questions were: could we put the pieces of the puzzle together and prove that they made a coherent picture? And could we guess at the missing pieces? The only way was through using a computational model, which allows us to do things impossible in experiments – provide solutions and guesses for the missing pieces. The fact that the pieces of our puzzle all fitted together to produce a single coherent picture is evidence that we (as a field) are converging on a complete theory for how the brain learns from reward.”

Discovery could lead to better treatment for CKD patients

Faculty scientist Dr Donald Ward has discovered that small changes in blood acidity levels could have detrimental impacts on the health of kidney disease patients.

Chronic Kidney Disease (CKD) affects roughly one in five men and one in four women between the ages of 65 and 74 in the UK. Dr Ward’s research, published in the Journal of the American Society of Nephrology, suggests that very small changes in the blood’s pH level prevent the body from accurately monitoring calcium levels. This causes too much of the hormone PTH to be released, which leads to a greater risk of artery damage when the body releases calcium and phosphate from the bones. This often proves fatal to CKD patients. Dr Ward explains:

 

“The diseased kidneys prevent the body from getting rid of both excess phosphate and excess acidity. So if that acidity also causes the body to release more PTH then this could compound the problem by releasing further phosphate from the bone. This vicious circle might accelerate the potentially fatal calcification of the arteries. What is so important about this research is that we have demonstrated that changes in PTH release can be prompted by very small changes in blood pH level. Before, it was assumed that only a larger change in acidity would cause problems for patients.”

The research was funded by Kidney Research UK. Elaine Davies, Director of Research Operations from the charity, says:

“Donald’s work has used novel pharmacological and molecular tools in generating these new findings which increase our knowledge about the complex balance that clinicians need to consider when treating patients with CKD.”

 

Mind the gap – new insight could lead to more effective drug treatments

Faculty researcher Professor Dan Davis has made a discovery that could improve drug treatments. Alongside his team at the Manchester Collaborative Centre for Inflammation Research (MCCIR), Professor Davis was investigating how different types of immune cells communicate with each other and how they kill cancerous or infected cells. Professor Davis says:

“We studied the immune system and stumbled across something that may explain why some drugs don’t work as well as hoped. We found that immune cells secrete molecules to other cells across a very small gap. This happens when immune cells talk to each other, and also when they kill diseased cells. But crucially, some types of drugs aren’t able to penetrate the gap between the cells. So they can’t easily reach targets within the gap and work effectively.”

Comparing molecules of different sizes, the team used microscopic imaging to see which ones could fit into the gap between an immune cell and another cell. Only the smaller molecules could penetrate the gap. They even found that when an immune cell attaches itself to another cell, it clears out all but the smallest molecules between them. Professor Davis explains:

“Our research demonstrates that any drugs targeting immune cells need to be very small. Antibody proteins, for example, are too big. They aren’t able to get into the gap between the cells – they’re even cleared away when cells meet. To make them more effective they must be smaller – which is something that GSK (GlaxoSmithKline) are working on.”

PhD student Adam Cartwright played a key role in the research, splitting his time between Professor’s Davis’s lab and GSK. He says:

“Being able to test out our theory with medicines that GSK has designed was fantastic.  The idea that something I found out can be used to develop treatments to help patients is incredibly exciting.”

Faculty researcher receives grant for pancreatic cancer project

Dr Jason BruceFaculty researcher Dr Jason Bruce has been awarded a grant of around £180,000 by The Pancreatic Cancer Research Fund (PCRF.)

PCRF have awarded a total of £1.2million to ambitious projects tackling the UK’s deadliest cancer. It is the second year that they have invested over £1million in a single funding round, enabling innovative research that could lead to new treatments for this aggressive and complex disease.

Dr Bruce’s work focuses on pancreatic cancer cells and the unique way that they extract energy from the nutrients which help them to survive and grow. The cancer cells use this energy source to pump calcium out of the cell. As high levels of calcium can be fatal to such cells, Dr Bruce’s project will aim to utilise new drugs and cut off the supply of energy to the calcium pumps. This would kill cancer cells whilst leaving healthy ones unharmed.  Maggie Blanks, PCRF’s founder and CEO, said:

“This is an amazing achievement, and it is thanks to the tireless fundraising of our supporters around the country who know that funding research is the only way to accelerate the development of new treatments and diagnostic tools that will improve patients’ chances of survival.”

New test could identify infants with rare insulin disease

Faculty research has led to a new test which could help to identify congenital hyperinsulinism at an earlier stage. This rare but

Needlesdevastating disease causes low blood sugar levels in babies and infants and can lead to lifelong brain damage and permanent disability. The condition occurs when cells in the pancreas release too much insulin and cause frequent low blood sugar episodes. In the most serious cases, the pancreas may need to be removed.

In more than two thirds of infants who suffer from congenital hyperinsulinism, the genetic causes are unknown. After analysing the genes and hormones of thirteen infants with the disease at Manchester Children’s Hospital, Dr Karen Cosgrove and her team discovered the new way of testing.

Their test measures a pair of hormones called incretins, which tell the cells in the pancreas to release more insulin to regulate sugar levels in our blood. When a child’s body releases more incretin hormones than is normal, the pancreas will release too much insulin. This will cause dangerously low blood sugar levels. Dr Cosgrove explained:

“This is the first step to understanding what causes the disease in these particular patients (with unknown genetic causes.)  In future, the test may influence how these children are treated medically, perhaps even avoiding the need to have their pancreas removed. Although we are the first researchers to report high incretin hormone levels in patients with congenital hyperinsulinism, further studies are needed to see if our test works on a larger group of patients.”

You can watch Dr Cosgrove discussing the research below:

Mining big data yields Alzheimer’s discovery

Faculty scientists have utilised a new way of working to identify a gene linked to neurodegenerative diseases such as Alzheimer’s. The discovery may help to identify which people are most likely to develop the condition.

The team compared genes in mice and humans. Using brain scans from ENIGMA Consortium and genetic information from The Brain scansMouse Brain Library, they were able to identify MGST3, a novel gene which regulates the size of the hippocampus in both mouse and human. This gene was shown to be linked to neurodegenerative diseases. Dr Reinmar Hager, senior author of the study, said:

“What is critical about this research is that we have not only been able to identify this specific gene, but also the networks it uses to influence a disease like Alzheimer’s. We believe this information will be incredibly useful for future studies looking at treatments and preventative measures.”

The team used two of the world’s largest collections of scientific data, The ENIGMA Consortium and The Mouse Brain Library. The ENIGMA Consortium is led by Paul Thompson, based at the University of California. It contains brain images and gene information from almost 25,000 subjects. The Mouse Brain Library, established by Robert Williams from the University of Tennessee Health Science Centre, contains data on over 10,000 brains and numerical data from more than 20,000 mice. David Ashbrook, a researcher in Dr Hager’s team, explained why combining the databases was so useful:

“It is much easier to identify a genetic variant in mice as they live in such controlled environments. By taking the information from mice and comparing it to human gene information, we can identify the same variant much more quickly. We are living in a big data world thanks to the likes of the Human Genome Project and post-genome technologies. A lot of that information is now widely shared. By mining what we already know we can learn so much more, advancing our knowledge of diseases and ultimately improving detection and treatment.”

For more information, please read the full paper which was published in BMC Genomics.

For further enquiries, please contact david.ashbrook@manchester.ac.uk

Discovery could lead to better melanoma treatment

A Faculty led research team has discovered that immune cells may be responsible for drug resistance in melanoma patients.

Melanoma cellsAlong with colleagues at the Cancer Research UK Manchester Institute, Dr Claudia Wellbrock found that chemical signals produced by immune cells known as macrophages also act as a ‘survival signal’ for melanoma cells. When the researchers blocked this signal – called TNF alpha – melanoma tumours were smaller and easier to treat. The research suggests that targeting this ‘survival signal’ could lead to new treatments. Dr Wellbrock says:

“This discovery shows that immune cells can actually help melanoma to survive. Particularly when patients are receiving treatment, the immune cells produce more of the ‘survival signal,’ which makes treatment less effective. So combining standard treatment with immunotherapy could provide more long-lasting and effective treatments to increase survival.”

Melanoma is the most deadly form of skin cancer with around 13,300 people diagnosed in the UK each year. Rates of the disease have increased more than fivefold since the 1970s. Professor Richard Marais, Director of the Cancer Research UK Manchester Institute, said:

“Melanoma is particularly difficult to treat as many patients develop resistance to standard treatment within a few years. This research provides a key insight into why this is the case. Drugs which block this ‘survival signal’ have already been developed; using these along with standard treatment may be a promising new approach for melanoma patients.”

Insulin offers new hope for the treatment of acute pancreatitis

Faculty scientists have discovered that insulin can protect against acute pancreatitis, a disease for which there is currently no treatment. The condition involves the pancreas digesting itself, resulting in severe abdominal pain, vomiting, and systemic inflammation. There are around 20,000 cases every year in the UK, with around 1000 proving fatal. There is currently no immediate cure. Dr Jason Bruce, the research team leader, said:

“The major causes of pancreatitis include bile acid reflux from gall stones and excessive alcohol intake combined with a high fat diet. When alcohol and fat accumulate inside pancreatic acinar cells — the cells that secrete digestive enzymes into the gut — the resulting small molecules (metabolites) deplete cellular energy levels and increase cellular calcium. This causes uncontrolled and catastrophic cell death and the cells burst, releasing their toxic enzymes, which digest the pancreas and surrounding tissue.”

However, recent research from Dr Bruce’s laboratory shows that insulin, which is normally released from the beta cells of the insulinpancreas, prevents the toxic effects of alcohol and fatty acid metabolites.

The team decided to look at insulin because it has been used to treat obese pancreatitis patients by reducing fatty acids on the blood. Diabetes makes pancreatitis worse and diabetics are at higher risk of developing the disease, but the team noticed that the incidence of pancreatitis is reduced in diabetics who receive insulin. Although tenuous, these findings suggested that insulin might have a protective role, but it remained unclear how the insulin was working. This research provides the first evidence that insulin directly protects from the disease in the acinar cells, the place of initiation. Dr Bruce explained:

“Insulin works by restoring the energy levels of pancreatic acinar cells, which fuels the calcium pumps on the cell membranes. These calcium pumps help to restore cellular calcium and prevent the catastrophic cell death and autodigestion of the pancreas. Although more research is needed to confirm that insulin works in animal models and human clinical trials, this study suggests that, combined with tight control over blood glucose, insulin may be an effective treatment for pancreatitis. Furthermore, if we can better understand how insulin works, then we might be able to design new and more effective drugs that might one day provide the first curative treatment for this disease”

Scientists closer to understanding why weight-loss surgery cures diabetes

Hormone cells interspersed throughout other intestinal cells

Faculty scientists are a step closer to understanding why diabetes is cured in the majority of patients that undergo gastric bypass surgery. It appears that the cure can be explained by the effect of surgery on ‘reprogramming’ specialised cells in the intestine that secrete powerful hormones when we eat. Dr Craig Smith, research leader on the study, said:

 “Our research centred on enteroendocrine cells that ‘taste’ what we eat and, in response, release a cocktail of hormones that communicate with the pancreas to control insulin release to the brain, convey the sense of being full, and optimize and maximize digestion and absorption of nutrients. Under normal circumstances these are all important factors in keeping us healthy and nourished. But these cells may malfunction, resulting in under- or over-eating.”

In the UK, approximately 2.9 million people are affected by diabetes. Among other factors, the illness is linked to genes, ethnicity, diet, and obesity. 75% of people suffering from both obesity and diabetes are cured of diabetes after a gastric bypass. Understanding how this surgery cures the disease is the crux of Dr Smith’s research:

“The most common type of gastric bypass actually also bypasses a proportion of the gut hormone cells. It is thought that this causes the cells to change and be reprogrammed. Understanding how they change in response to surgery may hold the key to a cure for diabetes. Our next challenge is to investigate the messages the gut sends out when we eat food and when things go wrong, as is the case in diabetes. We hope this work will result in the development of drugs which could be used, instead of surgery, to cure obesity and prevent diabetes.”

Scientists find trigger that creates different kinds of cell

A graphical abstract of the studyFaculty scientists have identified an important trigger that dictates how cells change their identity and gain specialised functions. The research brings them closer to being able to understand how complex organisms develop. This new knowledge will improve future research into how cells can be artificially manipulated. Professor Andrew Sharrocks, lead author on the study, said:

“Understanding how to manipulate cells is crucial in the field of regenerative medicine, which aims to repair or replace damaged or diseased human cells or tissues to restore normal function.”

The team focused on part of the genome that helps determine where and when a gene is expressed, known as an ‘enhancer.’ Different enhancers are active in different cell types, allowing the production of distinct gene products in different tissues. In this study, the team determined how these enhancers become active. Professor Sharrocks said:

“All of us develop into complex human beings containing millions of cells from a single cell created by fertilization of an egg. To transit from this single cell state, cells must divide and eventually change their identity and gain specialised functions. For example, we need specific types of cells to populate our brains, and our recent work has uncovered the early steps in the creation of these cells. One of the most exciting areas of regenerative medicine is the newly acquired ability to manipulate cell fate and derive new cells to replace those which might be damaged or lost, either through old age or injury. To do this, we need to use molecular techniques to manipulate stem cells which have the potential to turn into any cell in our bodies.”

One of the current drawbacks in the field of regenerative medicine is that the approaches can be relatively inefficient, largely because scientists do not fully understand the principles that control cell fate determination. Professor Sharrocks added:

“We believe that our research will help to make regenerative medicine more effective and reliable because we’ll be able to gain control and manipulate. Our understanding of the regulatory events within a cell shed light on how to decode the genome”

An insight into stroke survival at the Pint of Science Festival

Stroke survivor Christine Halford and her daughter NatalieA stroke survivor and her daughter told their story in a Manchester pub as part of a three-day science festival in Manchester. The Pint of Science Festival took place across Manchester, bringing Faculty experts together with members of the public.

The festival provided an opportunity to hear about current research, discuss a range of topics over a drink, and take part in science-based pub quizzes and games. Each of the four Manchester pubs involved hosted a different scientific theme. In ‘Understanding Stroke’, part of the Stoke Association’s Action on Stroke Month, Professor Stuart Allan provided an insight into the brain of stroke survivors. Professor Allan said:

“We know that brain damage occurs within minutes of a stroke and that the quicker we can intervene to stop the processes that contribute to the death of brain cells the better.  With the advancements in stroke research in the last 20 years we know much more about these damaging events and that there can be brain repair post-stroke, meaning stroke patients now have a better chance of survival and recovery.”

The highlight of the event was provided by stroke survivor and nurse Christine Halford and her daughter Natalie, who offered moving first-hand accounts of their experiences of stroke. Natalie said:

“It’s imperative to raise awareness of stroke because nobody thinks it’s going to happen to them, until it does and your life is turned upside down. Stroke can happen to anybody of any age, at anytime and anywhere, which is why research is necessary as we still don’t have all the answers. The pub is a great setting as we can reach out to people who ordinarily would know nothing about stroke.”

Computer models helping to unravel the science of life

Scientists have developed a computer modelling simulation to explore how cells of the fruit fly react to changes in the “Cell, Martin Baron et al.”environment. The research is part of an ongoing study that is investigating how external environmental factors impact on health and disease.

The simulation shows how cells of the fruit fly communicate with each other during their development. The current phase of the study looks at how temperature affects cell signalling networks during development. This will help explain how flies – and other organisms – develop across a wide range of temperatures. Dr Martin Baron, lead researcher on the study, said:

“It is exciting that the computer model was able to make predictions that we could test by going back to the fly experiments to investigate the effects of different mutations which alter the components of the cells. It shows us that the model is working well and provides a solid basis on which to develop its sophistication further.”

The next phase of the study will see the team research how cell signalling networks adjust to other environmental changes, including nutrition. Dr Baron said:

“There is a lot of interest in how environmental inputs influence our health and disease by interacting with our genetic makeup. Our initial studies have already shown that changes to the adult fly’s diet can also affect how cells inside a fly communicate with each other and produce responses in certain fly tissues. This is a promising avenue for future studies.”

Baron explains that there are wider implications for understanding human health and disease:

“Many different types of signal control normal development but when some of these signals are mis-activated they can result in the formation of tumours. What we’ve learnt from studying the flies is that some communication signals can arise in different ways and this means that, in cancer, mis-activation of these signals can also occur by different routes. This is important because it can help us to understand how to stop mis-activation from occurring.”

New research links body clocks to chronic lung diseases

pulmonary-fibrosisFaculty research has shown that the body clock’s natural rhythm could be utilised to improve therapies that delay the onset of chronic lung disease. Dr Qing-Jun Meng and his team have discovered a rhythmic defence pathway in the lung, controlled by our body clocks, which is essential to combatting exposure to toxins and pollutants.

The team have found that the circadian clock in the mouse lung rhythmically switches genes on and off, controlling the antioxidant defence pathway. This 24-hourly rhythm enables the lungs to anticipate and withstand exposure to pollutants on a daily basis. Dr Meng said:

“We used a mouse model that mimics human pulmonary fibrosis, and found that an oxidative and fibrotic challenge delivered to the lungs during the night phase, when mice are active, causes more severe lung damages than the same challenge administered during the day, a mouse’s resting phase. Our findings show that timed administration of the antioxidant compound sulforaphane effectively attenuates the severity of the lung fibrosis in this mouse model.”

The research suggests that paying attention to the lung clock could increase the effectiveness of drug treatments for oxidative and fibrotic diseases, allowing for lower doses and reduced side effects.

Research team member Dr Vanja Pekovic-Vaughan said:

“This research is the first to show that a functioning clock in the lung is essential to maintain the protective tissue function against oxidative stress and fibrotic challenges. We envisage a scenario whereby chronic rhythm disruption (during ageing or shift work, for example) may compromise the temporal coordination of the antioxidant pathway, contributing to human disease.”

This study is a part of ongoing research exploring how chronic disruption to body clocks contributes to conditions such as osteoarthritis, cardiovascular disease, breast cancer, and mood disorder. Dr Meng said:

“Our next step is to test our theory that similar rhythmic activity of the antioxidant defence pathway also operates in human lungs.  This will enable us to translate our findings and identify the proper clock time to treat chronic lung diseases that are known to involve oxidative stress.”