News in brief
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MICRA Celebrates 1000 Members with Two New Co-Directors
Professor Nancy Papalopulu Becomes a Fellow of the Academy of Medical Sciences
Two University Institutes Secure €3.4million to Train Future Generation of Investigators
Video Reveals Cancer Cells' Achilles' Heel
A Hub for Engineering and Exploiting the Stem Cell Niche
Exciting Breakthrough in Search for Neurodegenerative Disease Treatments
Paired Fins of Fossil Fish Could Have Implications for Human Evolution
Monkey Study Reveals Why Middle Managers Suffer Most Stress
University and UMIP Runners Up in BBSRC Award
Worm Wagon Team Win International Women's Day STEM Award
Extinct giant camel found in Arctic discovery
Retirement of Janet Vale
Faculty at the Forefront of Inflammatory Bowel Disease Network
Cell Movement Explained by Molecular Recycling
Understanding How Cells Stick
Important Advances in Treatment of Eye and Kidney Conditions
World First for Fly Research
Budding Researchers to Experience Cutting-edge Research Thanks to Pioneering Project
New Use for Old Drug Could Bring Hope to Alzheimer's Patients
Secrets of a Tadpole’s Tail Could Have Big Implications for Human Healing
May 2013
MICRA Celebrates 1000 Members with Two New Co-Directors
The Manchester Interdisciplinary Collaboration for Research on Ageing (MICRA) is celebrating its 1000th member following the announcement of two new co-directors. Professors Cay Kielty and Dean Jackson, both from the Faculty, have joined the existing leadership team of James Nazroo, Chris Phillipson, Alistair Burns, and Neil Pendleton to support the continued growth and development of MICRA across the University and beyond. Until recently, Cay was Associate Dean for Research in the Faculty and she now leads on cross faculty working. She holds a chair in medical biochemistry with a focus on regenerative medicine. Dean is a cell biologist, the Head of Section for Cellular Systems, and a member of the FLS Senior Management team.
MICRA has a diverse membership built up over three years as a network promoting interdisciplinary research on all aspects of ageing. Membership is open to anyone interested in this field and has attracted academics, students, voluntary sector providers, staff from the NHS, the private sector, and the government, as well as many older people. Most members have attended MICRA events, including the monthly public seminars in which academics from different disciplines present alongside practitioners on key ageing issues. Seminars are now regularly attracting audiences of around 100, looking at topics such as ‘Ageing, Dementia, Creativity and Storytelling’ and ‘Population Ageing and the Future of Cities.’ 115 attended last month’s public lecture by Dr Aubrey de Grey. You can join MICRA by following the link at the bottom of their homepage.
Professor Nancy Papalopulu Becomes a Fellow of the Academy of Medical Sciences
Professor Nancy Papalopulu has been elected to the Fellowship of the Academy of Medical Sciences as recognition for her contribution to the advancement of medical science. Out of 351 candidates, Professor Papalopulu was one of only 44 UK researchers to be recognised in this year’s list.
To be elected as an Academy Fellow, a scientist must display excellence in medical research, show innovative applications of scientific knowledge, or provide eye-catching service to healthcare. Professor Sir John Tooke, President of the Academy of Medical Sciences, said:
“The Academy of Medical Sciences exists to promote the best of medical science for the benefit of society. Our new Fellows are recognised for their exceptional contribution and collectively represent the array of talent present in the UK medical science community. They will further strengthen the Academy and I look forward to working with them over the coming years.”
Professor Papalopulu joined the Faculty from The University of Cambridge in 2006. Her research studies the development of the nervous system from fertilised egg to embryonic brain. Her work focuses on understanding how cells decide to divide or differentiate at the molecular level; a decision which is crucial for the correct development of the nervous system. Most recently, she made an important discovery into how cyclical fluctuations in levels of protein and small RNAs regulate the fate that cells adopt.
This research into the nervous system could prove integral to the treatment of many medical conditions. It is for this work, and the role she plays in helping future scientists to undertake similar crucial research, that Professor Papalopulu has been recognised as a Fellow of the Academy of Medical Sciences. Professor Papalopulu discussed her election to the Academy:
“Basic research underpins medical discoveries and it is a great honour that my research has been recognised in this way by the country’s leading medical scientists. I am looking forward to serving the community as a Fellow of the Academy of Medical Sciences.”
The Faculty would like to offer our heartfelt congratulations.
Two University Institutes Secure €3.4million to Train Future Generation of Investigators
The Manchester Institute of Biotechnology (MIB) and Photon Science Institute (PSI) have secured a Marie Curie training network grant worth €3.4 million to train the future generation of investigators. The four year grant entitled “MAGnetic Innovation in Catalysis”, known as the MAGIC Innovative Doctoral Programme, will see the MIB and PSI host 12 early stage researchers who will be appointed to three-year PhD training programmes. The University of Manchester will partner with six Universities (Tokyo, Freiburg, Lund, Joseph Fourier in France, Edinburgh and Copenhagen) and five companies (AZ, Bruker, TGK, Conformetrix, and SarOMICS). Each early stage researcher will be closely linked to the international and industrial partners who will be actively involved in their research projects. Professor Nigel Scrutton, Director of MIB, said:
“The concept of team-based activity is well founded across research groups in MIB and PSI and will enrich the training experience by bringing multiple skills embedded in these teams to MAGIC programmes. Our aim is to train the future generation of leading investigators of biological catalysis/enzymology in developing new enabling technologies that can advance physical understanding of catalysis and mechanism. These collaborative research projects will explore the mechanistic details of enzyme systems by adopting innovative, versatile and unique experimental techniques to probe the contributions of motions across multiple spatial and temporal timescales and quantum chemical effects. In turn, these novel methods will transform current experimental capabilities and will be applied to a range of important biological catalysts to probe the mechanistic importance of coupled motions and quantum physico-chemical effects.”
It is expected that this grant will commence in February 2014.
April 2013
Video Reveals Cancer Cells' Achilles' Heel
Professor Dan Davis and his team at the MCCIR have discovered why the cancer drug rituximab kills cancerous B cells so effectively. The drug is widely used in the treatment of B cell malignancies such as lymphoma and leukaemia, as well as with autoimmune diseases such as rheumatoid arthritis. The findings could be integral to the design of future cancer treatments.
Using high-powered laser based microscopes, researchers made videos of the process by which rituximab binds to a diseased cell and then attracts white blood cells, known as natural killer (NK) cells, to attack. They discovered that rituximab tended to stick to one side of the cancer cell, forming a cap and drawing a number of proteins to that side. Effectively, it caused a front and back to the cell – with a cluster of protein molecules on one side.
What most surprised the scientists was how this changed the effectiveness of NK cells. When NK cells latched onto a rituximab cap which had already drawn a protein cluster to one side of the cell, it killed the cell 80% of the time. Without the cluster of proteins, it killed only 40% of the time. Professor Davis said:
“These results were unexpected. It was only possible for us to unravel why this drug was so effective through the use of video microscopy. Watching what happened within the cells, we could identify why rituximab is so effective. It tended to reorganise the cancerous cell, making it especially prone to being killed. Our findings demonstrate that the ability to polarise a cell by moving proteins should be considered when new antibodies are tested as potential cancer treatments. It appears they can be twice as effective if they bind to a cell and reorganise it.”
Dr Matt Sleeman, Senior Director of Biology at MedImmune, said:
“This great observation can influence how we as a biotech company identify and design future therapies. It shows how innovative thinking can be achieved by working with top academics. I am excited by the potential of the MCCIR to bring further innovation and ultimately bring benefits to patients. ”
A Hub for Engineering and Exploiting the Stem Cell Niche
Faculty professors Sue Kimber and Cay Kielty are partners in a new cross-university consortium which will form a research platform to address the gaps in knowledge, the challenges, and the opportunities for regenerative medicine offered by stem cells and their microenvironment (‘niche’). This hub will bring together world-leading expertise from Manchester, Edinburgh, KCL, Cambridge, Bristol, ICL, and Keele. The consortium is funded by an award to the UK Regenerative Medicine Platform, led by the Medical Research Council.
The hub aims to discover and deliver niche-based approaches to regenerative medicines by focusing on exemplar tissues such as cartilage. It will establish a platform of cutting-edge technologies which the UK community can apply to a spectrum of disease in which the failure of tissue repair causes societal suffering and economic hardship.
The overall objective of the hub is to promote the regeneration of healthy tissues by identifying the niche signals that direct stem cells to restore tissue function. This knowledge will allow stem cells to be regulated using biological agents, drugs, and other methods, and thus be exploited therapeutically. They also anticipate that new understandings of the abnormal niche created by inflammation following tissue damage will improve the effectiveness of repair by transplanted cells.
The consortium’s funding will help UK scientists overcome barriers in this emerging field, allowing them to transform laboratory discoveries into the most effective clinical applications. Regenerative medicine is a relatively new field of science, but with its great potential to repair or replace damaged tissues, it could provide therapies for as yet incurable conditions such as heart disease, Parkinson’s, blindness, osteoarthritis, and liver failure. Minister for Universities and Science David Willetts said:
“Regenerative medicine is a hugely promising area of science, which is why it featured in our Strategy for UK Life Sciences and was identified as one of the eight great technologies. This investment will help take excellent basic research through to clinical application, benefitting patients and driving growth.”
Exciting Breakthrough in Search for Neurodegenerative Disease Treatments
Faculty scientists have taken a significant step towards developing an effective treatment for neurodegenerative diseases such as Huntington’s, Alzheimer’s, and Parkinson’s. Manchester Institute of Biotechnology researchers have detailed how an enzyme in the brain interacts with a drug-like lead compound for Huntington’s, inhibiting its activity. Their findings demonstrate that this can be developed as an effective treatment for these difficult to treat conditions.
Working with colleagues at the Universities of Leicester and Lisbon, the researchers identified the molecular structure of the enzyme kynurenine 3-monooxygense (KMO), found in the human brain. This is the first time the crystal structure of KMO has been established, and the process took five years to complete.
The scientists then studied how the compound UPF 648 binds incredibly tightly to the enzyme, acting as an inhibitor. Previous studies had shown that switching off the enzyme activity through drug binding should be effective when treating brain disorders. Professor Nigel Scrutton, who led the study, said:
“UPF 648 works effectively as an enzyme activity inhibitor. However, in its current form it doesn’t pass from the blood into the brain. Our research enables a search for new KMO inhibitors that are able to cross the blood-brain barrier. This provides real hope for developing drug therapies for diseases such as Huntington’s, Alzheimer’s, and Parkinson’s. ”
Dr Flaviano Giorgini from the University of Leicester said:
“This is a big move forward for the development of KMO inhibiting drugs. It is hoped that such compounds may ultimately be tested in clinical trials and prove beneficial for patients.”
Cath Stanley, Chief Executive of the Huntington's Disease Association, welcomed the findings:
“This research is a really exciting piece of the jigsaw that enables us to understand a little more and takes us a step closer to being able to provide an effective treatment for Huntington’s Disease”
Paired Fins of Fossil Fish Could Have Implications for Human Evolution
According to Faculty scientist Dr Robert Sansom, the discovery of paired fins behind the anus of an unusual fossil fish could have implications for human evolution. The fins were identified on Euphanerops, a fossil jawless fish that swam in the seas around 370 million years ago. The find makes the fish one of the first vertebrate to develop paired appendages. However, as Dr Sansom explains, the positioning of the fins is very unusual:
“Euphanerops is unique because its anal fin is paired, meaning there is one fin on each side of the fish. Until now anal fins have only been seen on jawed fish and have been unpaired. Euphaerops’ age is important as it dates from a time of deep evolutionary split between jawed and jawless fish, the two main divisions of vertebrates alive today. It represents an important stage in the evolution of paired appendages. It’s unclear why the fins are so far back on the fish, or what advantaged they might have provided. However, they do show that our early vertebrate ancestors tried out many different body plans before settling on two arms and two legs. Our bodies could have looked very different!”
Dr Sansom discovered the paired fins while studying Euphanerops fossils in Quebec. The research followed on from a 2009 study of early vertebrate evolution and fossil preservation with colleagues from The University of Leicester. Their findings have been published in the Royal Society’s journal Biology Letters. Dr Sansom says it was an exciting find:
“The unusual paired anal fin of Euphanerops lends support to the idea that there was some degree of developmental and evolutionary experimentation in fish. After the Devonian period and the extinction of a lot of species, the jawed vertebrate body exhibits fewer deviations from the formula of paired pectoral, paired pelvic, unpaired dorsal, and unpaired anal appendages. The discovery of new anatomical conditions will hopefully shed more light on the timing and sequence of the events underlying the origin and diversification of vertebrate appendages.”
Monkey Study Reveals Why Middle Managers Suffer Most Stress
Dr Susanne Shultz, a Royal Society University Research Fellow in the Faculty of Life Sciences, recently oversaw a study into monkeys which reveals why middle managers of the human variety suffer the most stress at work. The study, undertaken by scientists at the Universities of Manchester and Liverpool, found that middle hierarchy monkeys are the most likely stress sufferers.
Katie Edwards, from Liverpool’s Institute of Integrative Biology, spent nearly 600 hours watching Barbary macaques at Trentham Monkey Forest. She monitored one female for a day at a time, recording all incidences of social behaviour. This included agonistic behaviours like threats and slaps, submissive behaviours such as displacing and screaming, and affiliative behaviours such as embracing and grooming. Faecal samples from the female were then collected and analysed for levels of stress hormones. Katie explains:
“Unsurprisingly, we recorded the highest level of stress hormones on the days following agonistic behaviour. Unlike previous studies that follow a group over a period of time and look at average behaviours and hormone levels, this study allowed us to link the observed behaviour of specific monkeys with their individual hormone samples from the period when they were displaying that behaviour.”
Another key aspect of the research noted where the observed monkey ranked in the social hierarchy. Those in the middle order had the highest recorded levels of stress hormones. Dr Shultz considers why:
“We found that monkeys in the middle of the hierarchy are involved in conflict with those below and above them, while those at the bottom are distanced from conflict. The middle ranking macaques are more likely to challenge, and be challenged by, those higher up the ladder.”
Katie says the results could also be applied to human behaviour:
“People working in middle management might have higher levels of stress hormones than their boss or the workers they manage. These ambitious mid-ranking people may face challenges of moving upwards, whilst also maintaining authority over lower-ranking workers.”
University and UMIP Runners Up in BBSRC Award
The University of Manchester and its technology transfer arm, University of Manchester Intellectual Property (UMIP), have been announced as joint runners-up in the Activating Impact category of the 2013 BBSRC Fostering Innovation Awards.
Activating Impact is a new category. It was created to celebrate the work of successful Knowledge Exchange and Commercialisation (KEC) teams or individuals who have made essential contributions in turning BBSRC supported bioscience research into real-life applications. The University places great emphasis on KEC and the Faculty is a major recipient of funding from the BBSRC.
The Faculty’s Associate Dean for Business Development, Professor Ian Kimber, has played a crucial role in the work that led to this award. Working closely with Dr Rich Ferrie, Head of UMIP, he helped create an intimate connectivity between the researchers and IP specialists.
This has contributed to the successful transfer of technology, and the subsequent healthcare impact, for many years. Ai2 Ltd and Conformetrix were just two examples recognised by the judges. Ai2 Ltd has developed anti-infective peptide technology for use in ophthalmics and medical devices, whilst Conformetrix have developed platform technology that uses nuclear magnetic resonance analysis to determine 3D molecular structures of drug compounds with high accuracy. This is a world first which allows Conformetrix to develop a pipeline of proprietary drugs for use against therapeutically important targets.
As joint runners-up, The University and UMIP will receive £25,000. This will help appoint an IP Impact Officer for one year, to work closely with Professor Kimber and Dr Ferrie on a pilot programme aimed at maximising impact from the pool of IP emanating from the Faculty. Professor Ian Kimber comments:
“I was delighted to learn that our bid was awarded joint second place in the finals. I believe this achievement recognises our commitment to developing new models and new mechanisms, ensuring that the fruits of our investment in research are exploited quickly and effectively to deliver real health and economic benefits.”
March 2013
Worm Wagon Team Win International Women's Day STEM Award
Faculty scientists Dr Sheena Cruickshank and Professor Kathryn Else, alongside Dr Joanne Pennock of The Faculty for Medical and Human Sciences, have received the International Women’s Day 2013 Award for Woman in Science, Technology, Engineering and Mathematics (STEM). The award is presented to women who have excelled in the STEM fields, and those having a positive impact on women or the wider community. The fact that the team have been chosen as this year’s recipients demonstrates just how successful they have been in their joint venture: The Worm Wagon.
The award-winning trio’s research focuses on Neglected Tropical Diseases, specifically soil transmitted parasitic worm infections. These illnesses have a huge impact on global health and often trap communities in poverty due to ill health and reduced schooling. A key 2020 goal for the World Health Organisation is to provide deworming medication to 75% of school-age children in endemic regions.
The Worm Wagon showcases this research and is enthusiastically supported by other members of the Manchester Immunology Group. Activities revolve around videos of hatching worm eggs, field work in Ecuador, and messy mucus demonstrations. These activities have been enjoyed by over 45,000 people at schools, festivals, and museums. The scientists have also worked with community organisations and women and children from Asian communities, raising awareness of parasitic worm infections.
At the 2010 Manchester Science Festival, the Worm Wagon created two pieces of traditional Indian art (Rangoli) to highlight the role that science can play in reducing world poverty. The artwork raised awareness of on-going research and highlighted the global drive to reduce worm infection in school children. The events were a great success, prompting interesting discussion and contributing to the scientific direction in Manchester.
The Worm Wagon team are all committed to encouraging and promoting women in science. Professor Else and Dr Pennock work on improving Athena Swan status for their Faculties, while Professor Else also founded the Women in Life Sciences group at the University. Receiving this latest award is a deserved achievement, recognising the successful and dynamic work done to improve the situation for female scientists at the same time as combatting serious illness.
Extinct Giant Camel Found in Arctic Discovery
Faculty researcher Dr Mike Buckley was recently drafted in to identify ancient fossilised bones discovered on Ellesmere Island of the High Arctic. The fossils were collected by Dr Natalia Rybczynski of the Canadian Museum of Nature, but her research team had been struggling to identify them.
Important characteristics suggested the fragments were part of a large tibia, the main lower-leg bone in mammals. Digital files were produced using a 3D laser scanner, allowing the 30 fragments to be assembled and aligned. Dr Buckley then used recently developed collagen fingerprinting techniques to determine that the bones belonged to an 3.5 million year-old giant camel. This is the first evidence of the creature in the High Arctic, and the furthest North that a camel has ever been discovered.
The identification involved extracting minute amounts of collagen from the fossils. Using a collagen profile the bones were compared to 37 modern mammal species and a fossil camel found in the Yukon. The collagen profile was almost an identical match to the modern day Dromedary and the Ice-Age Yukon giant camel. Dr Buckley explained:
“This is the first time that collagen has been extracted and used to identify a species from such ancient bone fragments. The fact the protein was able to survive for three and a half million years is due to the frozen nature of the Arctic. This has been an exciting project to work on and unlocks the huge potential collagen fingerprinting has to better identify extinct species from our preciously finite supply of fossil material.”
Dr. Rybczynski says the discovery sheds new light on modern camels:
“We now have a new fossil record to better understand camel evolution, since our research shows that the Paracamelus lineage inhabited northern North America for millions of years, and the simplest explanation for this pattern would be that Paracamelus originated there. So perhaps some specialisations seen in modern camels, such as their wide flat feet, large eyes and humps for fat may be adaptations derived from living in a polar environment.”
Retirement of Janet Vale
The Faculty bid a fond farewell to Janet Vale on the 28th February 2013, following her retirement from the University. Janet began working here in 1966, and, if we consider her time as an undergraduate, has been a member of the Manchester family for over fifty years. After graduating, she immediately joined the staff as a Research Assistant in Pharmacology and Ophthalmology. Despite escaping to work in Sweden for a year, she would later become a lecturer in the same fields, remaining so until her recent retirement. Janet’s high levels of achievement as a lecturer, and in the many other roles she fulfilled, led to her being presented with a Distinguished Achievement Award from the University.
Janet’s work also extended beyond the teaching of Faculty of Life Sciences students. She was a Non-Residential Advisor at Whitworth Park Halls of Residence from 1975 onwards, a Senior Advisor in the Student Guidance Service, an important part of the University Ethics Committee, and, in perhaps her favourite role, she was the Secretary of The University Wine Club. That is one role she hopes to continue past her retirement.
Never one to let things get dull, Janet has also spent several summers teaching pharmacology in Tanzania. During this time she took advantage of her environment to climb Mount Kilimanjaro. She has also twice taken part in the BOGLE walk for Manchester RAG, and in 2011 she completed lectures wearing a red nose, raising £270 for Comic Relief. Despite raising much more than she’d expected, Janet did not renege on her promise to match whatever her students donated.
Janet says that the students were always the most important thing to her. She even worked as a pharmacist on Saturday afternoons to ensure that she kept up-to-date with developments, and could provide the best possible teaching to those students. As most of her time was split between teaching and student support, it will be these interactions that she misses the most. We can be sure that her students, and all at the University, will miss the presence of such a valued character in the University’s corridors.
Faculty at the Forefront of Inflammatory Bowel Disease Network
Faculty researcher Professor Werner Müller is the Scientific Coordinator for a new €12 million systems research network, created to identify better treatments for Inflammatory Bowel Disease. The network, called SysmedIBD, includes universities and companies from the UK, Germany, the Netherlands, Israel, and New Zealand.
The five year project is aiming for a better understanding of the disease. To achieve this, the team will attempt to identify risk genes, investigate the effects of diet, and develop methods for better prediction of treatment for patients. The research network will use the systems medicine approach. This utilises specific patient details to build mathematical models and provide the best possible treatments for each individual. Professor Müller explains:
“This systems medicine approach will lead to a better personalised diagnosis and treatment of patients. We will target the central pathway of inflammation in the hope that by understanding the signalling processes we can eventually manipulate them. IBD affects every patient differently making it difficult to develop effective treatments. Current treatments are very expensive and many patients develop resistance to the drugs. We hope that this intense programme of research will help us to overcome the current limitations of treatments for this incurable condition.”
The term IBD refers mainly to Crohn’s Disease and Ulcerative Colitis. Both conditions are chronic long-term diseases that involve inflammation of the gastrointestinal tract. In the UK, IBD affects about one person in every 350. This new network aims to bring relief to these people. Professor Jonathan Rhodes from the collaborating group at the University of Liverpool says:
“This is a great boost for Inflammatory Bowel Disease research in the UK and stands an excellent chance of leading to benefits for patients.”
Funding for the project has come from the European Union’s Seventh Framework Programme. The €12 million grant is being shared between 12 participants, with the largest share, €2.5 million, coming to The University of Manchester.
February 2013
Cell Movement Explained by Molecular Recycling
Faculty scientists have identified how cells control the recycling of molecules, a process which is essential for their movement. This discovery provides a better understanding of how our bodies heal wounds.
Dr Mark Morgan and his team at the Wellcome Trust Centre for Cell Matrix Research have been studying the role of integrins in this process. Integrins are molecules capable of grabbing hold of the fibres that surround the cell, allowing the cell to drag itself along. However, there are several types of integrin on the cell surface and their varying properties affect how quickly the cell moves.
Once used by the cell, integrins are moved inside the cell and stored. When necessary, they are recycled back to the surface where they can once again bind with the surrounding fibres. Dr Morgan’s team uncovered the method by which cells control the type of integrins recycled. They found that Syndecan-4, another cell surface molecule, is able to detect and interpret subtle changes in the cell’s surface and respond accordingly. Dr Morgan says:
“Syndecan-4 plays a critical role in regulating wound healing, so, ultimately, we hope that this work will inform the development of novel therapeutic strategies to improve wound healing.”
The team identified the role of Syndecan-4 using sophisticated imaging techniques to study the movement of fibroblast cells. Dr Morgan explained their findings:
“When we changed the way Syndecan-4 senses the environment outside the cell, we were able to alter the way that it transmits signals into the cell and control integrin recycling. By manipulating the molecules in this way we found that we could either force the cells to move in a fast forward motion or stop altogether.”
The team plan to investigate how Syndecan-4 can be manipulated to control cell movement, and if new wound healing strategies can be developed as a result. They will also test whether this mechanism is involved in tumour progression and metastasis as disruptions in cell movement are often seen in cancer, vascular disorders, and chronic inflammatory disease.
Understanding How Cells Stick
Faculty researchers and scientists from the Georgia Institute of Technology have generated new insights into how cells stick to each other and to tissue structures known as extracellular matrices. These are essential functions in the formation of organs and organisms. Abnormalities in these areas are thought to play important roles in a range of disorders involving cell adhesion and movement, including cardiovascular disease and cancer.
The findings outline a surprising aspect of cell adhesion, involving molecules known as integrins. The research uncovered a phenomenon termed ‘cyclic mechanical reinforcement,’ in which the length of time bonds between cells and their surroundings exist is extended through repeated pulling and release between the integrins of the extracellular matrix. Professor Martin Humphries, Dean of the Faculty, says the study suggests new capabilities for cells:
“This paper identifies a new kind of bond that is strengthened by cyclical applications of force, and which appears to be mediated by shape changes in integrin receptors. The findings shed light on a possible mechanism used by cells to sense extracellular topography and to aggregate information through ‘remembering’ multiple interaction events.”
Cheng Zhu, a professor at Georgia Tech, had this to say:
“Many cell functions depend on cell interaction with the ligands of the extracellular matrix. The cells respond to their environment, including many mechanical aspects. This study extended our understanding of how connections are made and how mechanical forces regulate interactions.”
Using delicate force measuring equipment, Professor Zhu and his collaborators studied adhesion between integrin and a protein component of the extracellular matrix known as fibronectin. Cyclic forces applied to the bond switched it from a short-lived state with lifetimes of roughly one second, to a long-lived state that can exist for more than one hundred seconds.
The researchers now hope to determine whether or not the cyclic mechanical reinforcement they observed is a universal property of cellular adhesion molecules. They hope to discover how cells use this cyclic mechanical reinforcement, so they can form a better understanding of the processes that allow cells to move together with the abnormal cellular adhesion mechanisms that occur in diseases.
Important Advances in Treatment of Eye and Kidney Conditions
Faculty scientists have made important discoveries regarding why our immune system attacks our own tissues, causing eye and kidney diseases. This research could pave the way to new treatments for the eye condition Age-related Macular Degeneration (AMD) and the kidney condition atypical Haemolytic Uremic Syndrome (aHUS).
Both conditions are associated with incorrectly controlled immune systems and a protein called CFH which is responsible for regulating a part of our immune system called the complement cascade. Genetic alterations in CFH are known to increase a person’s risk of developing either AMD or aHUS, but rarely both. The reasons for this have remained unexplained until now.
Research teams led by Professor Paul Bishop and Professor Tony Day have expanded on previous work which demonstrated how a single common genetic alteration in CFH prevents it from fully protecting the back of the human eye. They found that the altered form of CFH couldn’t bind properly to a layer under the retina called Bruch’s membrane. This resulted in low-level inflammation and tissue damage, and, eventually, AMD.
In their most recent study, the Manchester researchers identified why certain CFH mutations result in diseases in specific tissues. Their studies showed that the region of CFH that helps protect the kidney had no effect in the eye. Instead, the other part of CFH, which is central to the AMD-associated genetic alteration, was crucial for protecting the eye, but did not contribute to the binding of CFH to kidney tissue. Their findings show, for the first time, that the level of importance of the two regions of CFH changes depending on which tissue the protein finds by itself. Dr Simon Clark said:
“Our findings suggest that the particular structure within the eye and kidney tissue determines precisely how and where CFH will bind. It’s as if the tissues have their own molecular postcodes. This is important because if we’re going to improve treatments for devastating diseases, such as AMD, we need to be able to develop tissue-specific therapies.”
World First for Fly Research
The Faculty of Life Sciences is at the forefront of fly research thanks to a unique scheme from Dr Andreas Prokop. Alongside Cambridge University’s John Roote, Dr Prokop has created the first ever basic training package for research using Drosophila, also known as the fruit fly. It’s hoped that more researchers will be encouraged to use the humble fly when studying conditions such as cancer and Alzheimer’s disease.
The Faculty is host to one of Europe’s biggest fly facilities. It provides temperature controlled rooms for storing fly stocks, dedicated work spaces to sort the flies, and high tech microscopes for training and experiments. The facility is currently used for various studies, with subjects ranging between evolution, cancer, sleep patterns, and drug tolerance.
Drosophila have been used for scientific research for over a century, but many scientists remain unaware of their value. To combat the difficulties that newcomers to flies may face because of this, Dr Prokop put together a training package for undergraduate students. The material assumed no prior knowledge of flies and took students back to basics.
Together with John Roote, Dr Prokop has now taken the student manual to the next level, developing it into a four part training package for all scientists. This includes an introductory manual, a practical session on gender and marker selection, a PowerPoint presentation, and a training exercise in mating scheme design. Sanjai Patel, who manages the Faculty’s Fly Facility, has already seen the impact of the training package:
“I was spending a lot of my time training students how to use the flies for their research. They would struggle with some of the basic concepts and kept coming back with questions. The training manual is self-explanatory. After they’ve been through it they’re usually confident enough to start using the flies.”
The training package has received positive feedback from all who have tested it so far. With the help of this new knowledge, it is hoped that more scientists will be encouraged to make use of the versatile fruit fly in their crucial research in the future.
January 2013
Budding Researchers to experience Cutting-edge Research Thanks to Pioneering Project
The Faculty of Life Sciences was central to a recent successful bid for funding from Research Councils UK (RCUK). As part of a University wide programme, the Faculty will play a key part in the pioneering School-University Partnerships Initiative, an RCUK campaign which aims to introduce young people from diverse backgrounds to cutting-edge research.
As one of only twelve institutions to succeed in their application, the University will receive a share of £3.5 million funding. RCUK hope that this cash injection will help to raise the aspirations of the young people involved, leading them to further study and success in their future lives.
As part of the University’s involvement Faculty staff and researchers will run a Life Sciences Summer School for Teachers. Teachers at schools and colleges will get a rare opportunity to update their knowledge on current research techniques as they undertake lab tours, hands-on practical work, and exclusive seminars. These experiences should equip teachers with the skills and information to confidently use contemporary research in the classroom and encourage research skills in their learners.
Many of the young people involved will come from groups currently under-represented at university, such as those in receipt of free school meals, those with experience of local authority care, and disabled pupils. Discussing the initiative, David Willetts, Minister for Universities and Science, said:
“Maintaining a good supply of scientists and researchers is vital to our economy and society, but to do this we need to draw talent from as wide a pool as possible. That is why the School-University Partnerships Initiative is so important.”
New Use for Old Drug Could Bring Hope to Alzheimer's Patients
Scientists working at PharmaKure, a drug discovery company spun out from The University of Manchester’s UMIP programme, are hoping that their research into new uses for old drugs may soon bring hope to Alzheimer’s patients. Alzheimer’s is the most common form of senile dementia, affecting more than 15 million people worldwide, and it is also the fourth biggest killer in Britain today, behind only heart disease, cancer, and stroke.
It is, therefore, a great concern that there are currently no drugs to cure Alzheimer's, and that the best available only alleviate symptoms for 6-12 months. However, based upon recent research, PharmaKure has just patented its first drug for Alzheimer’s treatment and is currently looking for investment to fund the necessary screening and trials.
The drug, known as PK-048, was first discovered in the 1980s. Envisaged as a drug candidate for Parkinson’s disease, it had never been tested for treatment of Alzheimer’s. Previous trials have shown that the drug is orally active, non-toxic, and crosses the blood-brain barrier, a crucial requirement for an Alzheimer’s drug. Commenting on trials of the drug, Dr Farid Khan, said:
“The potential for PK-048 to help alleviate the symptoms and potentially cure Alzheimer’s disease is really exciting. 30% of all newly marketed medicines are either existing drugs or formulations of old drugs which have been shown to be safe in patients. If these can be found to work for other diseases then development costs and risks can be drastically reduced, creating a huge investment potential.”
Discussing the potential of the research on PK-048 and other drugs which could have new uses, MSP Chief Executive, Rowena Burns, added:
“The impact of PharmaKure’s research will have a worldwide reach and help to cement Manchester’s reputation as a centre of excellence in life sciences.”
Secrets of a Tadpole’s Tail Could Have Big Implications for Human Healing
Professor Enrique Amaya and his team at the Healing Foundation Centre have been trying to better understand the remarkable regenerative capacities of frogs and salamanders in the hope that their research may improve human ability to heal and regenerate. During their studies, focused on tadpole tail regrowth, the team made a surprising and exciting discovery.
Unexpectedly, during their research, it was discovered that several genes involved in metabolism were activated during tail regeneration, particularly genes linked to the production of reactive oxygen species (ROS). The most surprising thing about these findings was that ROS are commonly believed to be harmful to cells. Discussing this research Professor Amaya said:
“We were very surprised to find these high levels of ROS during tail regeneration. Traditionally, ROS have been thought to have a negative impact on cells, but in this case they seemed to be having a positive impact on tail re-growth. When we decreased ROS levels, tissue growth and regeneration failed to occur. Our research suggests that ROS are essential to initiate and sustain regeneration response. We also found that ROS is essential to activate signalling activity implicated in essentially every studied regeneration system, including those found in humans.”
The next step for the team at the Healing Foundation Centre will be to study ROS and their role in healing and regenerative processes more clearly. With a better understanding, Professor Amaya and his team hope to apply their findings to human health and identify whether manipulating ROS levels in the body could improve our ability to heal and regenerate tissues. Although there is still a long way to go, these early findings may prove crucial to the future of regenerative medicine.