Biological Sciences New Boundaries 2014

Biological Sciences New Boundaries 2014

Centre for Biological Sciences

Protecting the jaguars of Belize

Preserving habitats in Central America Revolutionary epigenetics

Maternal health and diseases in later life

Understanding memory loss in Alzheimer’s disease Pioneering neuroscience research

Groundbreaking veterinary drugs Postgraduate research into new veterinary treatments

In this issueWelcome to Biological Sciences New Boundaries. In this issue, you will discover how our research is addressing some of the most challenging issues facing our world, from investigations into the molecules that form the building blocks of life, to the protection of endangered species in rainforests.

On page four, find out how researchers at Southampton are helping to protect the habitats of jaguars in the small Central American country of Belize, funded by a Darwin Initiative grant from the UK Government.

On page 10, read about how Professor Karen Lillycrop is looking at how changes at a molecular level to a baby’s genes before birth, can play a part in their future risk of disease.

Research into proteins, their structures and functions is world-leading at Southampton. Find out more in an interview with Dr Paul Skipp on page 14.

With diagnosed cases of Alzheimer’s disease set to rise to 135.5 million by 2050, Southampton academics are pioneering research into the proteins that are necessary for synaptic plasticity – considered to be the primary mechanism by which memories are stored in the human brain. Read more on page 16.

Continuing with the theme of tackling major societal challenges through our work, postgraduate research at Southampton has led to the development of new veterinary drugs. You can read more about this on page 20.

For more information, visit our website www.southampton.ac.uk/biosci/research

Please send us your feedback

We are keen to receive any feedback you have about Biological Sciences New Boundaries. If you have any comments or suggestions, please send them to [email protected]

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More highlightsUsing proteins to unlock the mysteries of diseasesGaining a full understanding of how genes produce proteins.Page 14

1 Protecting the jaguars of Belize Helping to preserve the jaguars’

habitat in Central America. Page 4

2 Revolutionary epigenetics Maternal health and diseases in later life.

Page 10

3 Understanding memory loss in Alzheimer’s disease

Neuroscientists at Southampton are playing a key role in new interdisciplinary research. Page 16

4 Groundbreaking veterinary drugs Interview with Dr Marcus Guest,

geneticist at Syngenta Crop Protection. Page 20

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Protecting the jaguars of BelizeFor the ancient Mayan, Aztec and Andean cultures of Central and South America, the jaguar symbolised strength and power. Although these big cats still roam freely through tropical and sub-tropical forests from southern North America to South America, their continued survival is now threatened by habitat loss and persecution. Research by Dr Patrick Doncaster and his former Southampton PhD students is helping to protect the jaguars’ habitat in the small Central American country of Belize.

“Without a wildlife corridor to protect this narrow strip from encroaching development, Belize’s southern and northern borders will no longer be linked by continuous forest, and the isolated southern forest will not sustain viable jaguar populations.”

Dr Patrick Doncaster, Reader in Population Ecology

4 Biological Sciences New Boundaries | University of Southampton

5Biological Sciences New Boundaries | University of Southampton

Jaguars need thousands of square kilometres of continuous forest to meet their needs for survival and reproduction. Patrick’s team has worked with the charitable organisation Panthera and the University of Belize to secure Belize’s first wildlife corridor for jaguars and other endangered cats. This forest corridor protects a unique link in the chain of continuous natural habitats within the Mesoamerican corridor stretching between South and North America. The corridor is now the only remaining connection between northerly and southerly forests at this latitude anywhere from the Atlantic to the Pacific.

The work was funded by a Darwin Initiative grant from the UK Government to Patrick at the University of Southampton. The case for the land to be included in Belize’s National Protected Areas Plan was made by his

collaborators in the country, Bart Harmsen from the University of Belize and Rebecca Foster from Panthera. Their fieldwork to collect the evidence base led to them establishing the first training framework in field conservation for Belizean students.

“All six species of cat in Central America are endangered by habitat loss,” says Patrick. “Although 60 per cent of land in Belize is still covered by forest, it is partitioned into northern and southern blocks, converging to a 20km strip bisected by the Western Highway, the country’s busiest trunk road. Without a wildlife corridor to protect this narrow strip from encroaching development, Belize’s southern and northern borders will no longer be linked by continuous forest, and the isolated southern forest will not sustain viable jaguar populations.”


Bart and Rebecca originally began researching large cats in Belize as Patrick’s PhD students, funded by the Natural Environment Research Council (NERC) and the Wildlife Conservation Society. They gathered extensive evidence of the ecology and behaviour of jaguars and pumas from camera traps and faecal remains in a large forest reserve and its surrounding unprotected farmland. These data were used to build computer simulations of their populations, which predicted that the cats were vulnerable to dying out in existing blocks of protected land unless these blocks were joined together by wildlife corridors. Following the research, Panthera recruited Bart as the Panthera Research Fellow at the University of Belize, and Rebecca as the Director of the Belize Jaguar Program.

In April 2011, Belize’s National Protected Areas Secretariat heard the case for the Corridor. During the meeting, Rebecca demonstrated the need to link up protected habitats for wildlife populations, based on the project’s monitoring and modelling. Her arguments persuaded the Secretariat to incorporate the 872km2 corridor into the National Protected Areas System Plan.

With the Darwin grant to Patrick, the University became one of the original funders of the Environmental Research Institute in Belize. This institute trained 89 undergraduates in its first three years, many of whom have gone on to work in government departments or to take further degrees.


Patrick has pursued his passion for wild mammals throughout his career. His first degree in Environmental Science at the University of East Anglia offered the opportunity to study ecology, a new option in the late 1970s. His PhD at the University of Oxford in the 1980s was one of the first research projects to study the ecology of urban foxes. “By equipping foxes with tracking devices, we discovered that they lived at much higher densities in towns than in the countryside,” he says. “Their social groups were smaller and uniquely dynamic, with territories that continually shifted in response to changing patterns of access in this finely divided landscape.” Patrick then moved to France for a project in marshland near Poitiers tracking the coypu, a 7-kg rodent native to South America. This species was introduced to Europe for the fur trade at the beginning of the last century, and established itself in the wild to become an invasive pest throughout Europe. It causes serious damage to arable farms by raiding crops and eroding the banks of watercourses. Patrick’s work on coypu populations in France and in their native Argentina showed how the species has adapted to its region

of introduction, while still remaining vulnerable to the harsher European winters. After completing this project, Patrick worked at the Université Pierre et Marie Curie in Paris on a study of flycatchers, demonstrating how these birds sustain healthy regional populations even in highly fragmented habitat, with a continuous exchange of individuals between forest patches. He then returned to the University of Oxford, this time to study the prey-predator interactions of hedgehogs and badgers in agricultural land. His large-scale manipulations of numbers of hedgehogs under controlled conditions in the field showed for the first time that badgers can regulate hedgehog population sizes and distributions.

Joining the University of Southampton as a lecturer in 1995, Patrick developed new interests in theoretical ecology and evolutionary biology while retaining his involvement with the biology of mammals. Current work on the evolution of co-operation and altruism in animals has led to an exploration of human behaviour in the face of impending climate change.

“Tackling global threats such as climate change requires a collective effort, which inevitably calls for some personal sacrifices,” Patrick says. “It remains a major problem to motivate cutting back on emissions of harmful greenhouse gases, at all scales from individuals in communities to governments on the global stage.” Patrick has been tackling this challenge in his undergraduate teaching by having the students play games of collective risk. He adds: “These role plays bring into sharp focus the trade- off between personal gain and public good that so often leads to a tragedy of the commons in which everyone is a loser. In the controlled setting of a game, students can safely explore alternative ways to cooperate with each other.” To find out more, visit www.southampton.ac.uk/biosci/wildlifecorridor


http://www.southampton.ac.uk/biosci/wildlifecorridor

Microbiological pipette in the genetic laboratory


Revolutionary epigenetics In the 1980s, University of Southampton scientist Professor David Barker pioneered the revolutionary new theory that common chronic diseases such as cancer, cardiovascular disease and diabetes could be affected by patients’ nutrition while in the womb.

His argument that the diet of a pregnant woman could influence the health of her children as they grew to adulthood is now widely accepted and has inspired much more research into the subject. Now, Professor Karen Lillycrop from the Centre for Biological Sciences at Southampton is exploring a further development of this concept, which suggests that changes at a molecular level to a baby’s genes before birth can play a part in their future risk of disease.

She says: “At a very early stage of life, molecules of CH3 are added to our DNA, which changes the activity of our genes to create structurally and functionally distinct cell types, such as nerve, blood and brain cells.” Karen continues: “Crucially, we now believe some of these alterations of the genes, induced in early life can affect our susceptibility to a range of diseases in later life.”

The altered methylation marks on the genes can be identified and regarded as ‘biomarkers’ indicating potential future health issues to researchers.

Karen explains: “Environmental factors in early life can affect the methylation of our genes, leading to persistent changes in gene activity and alterations in metabolism.”

Scientists believe the causes of these abnormalities are not solely about nutrition; factors such as exercise, stress and even maternal love have also been shown to affect methylation.

Karen has discovered that the process where a child develops a predisposition to diseases, can be reversed and there is potential to develop treatments: “In theory, reversing the process is possible but it would involve making very subtle changes to cells at the molecular level. It is a very delicate process, as it would be very easy to cause more harm than good,” she says.

At Southampton, Karen and her colleague Dr Graham Burdge are also investigating whether such effects can be passed from one generation to the next. Their results already suggest there is a distinct connection between nutrition

in pregnancy and the health of offspring, and even grandchildren.

“This transgenerational aspect of the research is so important because our findings show that what your grandmother and grandfather ate may influence your DNA and gene activity too. That is why getting maternal health right is so important to avoid cycles of obesity and reduce non-communicable diseases,” adds Karen.


Global epigenetics research

The researchers have joined forces with academic colleagues around the world who are working on epigenetics and building partnerships with private sector partners including Nestlé and Abbott Nutrition, who are interested in improving the health and wellbeing of their customers. This international collaboration, the EpiGen Consortium was established in 2006 at Southampton. It brings together 200 leading researchers in six organisations in three countries and has

attracted considerable research grants. The Consortium comprises researchers from Southampton, Liggins Institute, University of Auckland, AgResearch New Zealand, the Medical Research Council and the Singapore Institute of Clinical Sciences. Working together with the MRC Lifecourse Epidemiology Unit and the Southampton NIHR Biomedical Research Unit in Nutrition, Diet and Lifestyle the aim of EpiGen (led in the UK by Southampton’s Professor Keith Godfrey, Professor Cyrus Cooper, Dr Graham Burdge and Professor

Karen Lillycrop) is to translate basic research in epigenetics into biomarkers and interventions to reduce the burden of non-communicable disease. In the UK, this translational research is centred around the Southampton Women’s Survey.

“This is an area of research that could bring significant benefits in the future. There is already a great deal that pregnant women can do now to ensure the good health of their children,” explains Karen. “We have to keep on emphasising the healthy living messages, encouraging people to cut down on sugar,

Supplements of folic acid are effective in cutting down on the possibility of developing conditions such as asthma and spina bifida


salt and fatty food and eat more fruit and vegetables. We know supplements of folic acid are effective in cutting down on the possibility of developing conditions such as asthma and spina bifida, and regular exercise is also important for people at all stages of life.” It is of vital importance to us that our research is translated from ‘bench to bedside’ in this way, by applying discoveries made in the laboratory to improve patient health wherever possible,” she adds.

Folic acid and cancer

The benefits of folic acid extend past the well known use of supplements during pregnancy. In 2013, Karen was awarded a £142,000 grant from the World Cancer Research Fund to investigate links between folic acid (vitamin B9) and the development of cancer.

Folic acid has been shown to protect against many forms of cancer including breast cancer, yet crucially, some studies have shown that in large doses, it may increase

cancer risk. The project is examining the relationship between folic acid and cancer risk, which will help us to develop advice on how much people should take.

Karen explains: “My work is aimed at improving our understanding of the basic mechanism by which folic acid might regulate the genes involved in cancer risk. This will give us insights into the fundamental biological processes that underpin the development of cancer and help devise new interventions to halt the disease.”

To find out more, please visit www.southampton.ac.uk/biosci/kal


The Centre is currently performing the largest proteomics experiment on asthma in the world


Q What is the Centre for Proteomic Research?

Sequencing the human genome was phenomenally important in the life sciences; the large-scale study of the proteins produced by these genes (Proteomics) is the next step. If you compare the achievement of charting our DNA to sending a man to the moon, achieving the same with proteins will be like landing a mission on Mars. There are many thousands of proteins in the human body, all key to controlling cellular processes. If we improve our knowledge of these proteins, we will be able to provide insight into the mechanisms of disease and discover new protein biomarkers to help with diagnosis. At the Centre, our eight-strong team use more than £2m of the latest mass spectrometry equipment to examine and measure the levels of these proteins at the molecular level.

Q How is your team involved with cutting-edge asthma research?

The Centre is currently performing the largest proteomics experiment on asthma in the world, analysing over a thousand samples from people with asthma across Europe to discover more about the different types of the disease. Working with Professor Ratko Djukanovic in Medicine at Southampton and more than 30 European academic and pharmaceutical partners, this major, five- year, €23m European Union research project is already

discovering that various sub-types (known as phenotypes) exist within severe asthma. This information will eventually help in the development of the next generation of drugs designed to target each type specifically. This high-throughput approach to research is contributing to the development of personalised medicine – the next big breakthrough in diagnosis and treatment.

Q What else are you working on?

Proteomics is an important research area for tackling many complex problems and issues both within the life sciences and in other areas. We have a number of collaborative research projects with Unilever investigating how chemicals interact with proteins in skin at the molecular level, to understand the process causing skin sensitisation – a process that can cause the skin condition allergic contact dermatitis. We are also investigating a range of infectious disease causing organisms including Mycobacterium tuberculosis, Streptococcus pneumoniae and Chlamydia.

Outside medical applications, we are working with oceanographers at Southampton investigating the tiny single-celled organism Emiliania Huxleyi or Ehux. This species of phytoplankton is very common in the world’s oceans. It secretes an ‘armour plating’ of calcium carbonate; their sinking to the sea bed disrupts the ocean carbon system making a difference to the amount of CO2 that can be stored in

the atmosphere and able to contribute to the CO2 greenhouse effect. Using proteomics, we are currently trying to understand how increasing levels of CO2 in the world’s oceans may affect Ehux.

Q How is your research interdisciplinary?

We contribute to a great deal of research across the University of Southampton. As well as the examples above involving scientists in many disciplines, our capacity to generate a high volume of data is valued by mathematicians who are interested in discovering new ways to extract more useful information using the shape of these large and complex datasets.

Q How do you see proteomic research developing in the future?

Proteomics is a discipline that is continually evolving. It has a huge future potential for answering major questions in biology and for bringing new clinical advances leading to improved clinical diagnosis and safer treatments. Within the Centre, we are currently developing new techniques that advance our understanding of how proteins interact with one another in different diseases, where these proteins are located within a cell or tissue, and how these proteins may be modified, important factors affecting their function.

For more information, visit www.proteome.soton.ac.uk

Using proteins to unlock the mysteries of diseasesResearch into proteins, their structures and functions is world-leading at Southampton. Dr Paul Skipp explains more about the groundbreaking research underway at the Centre for Proteomic Research.


In 2013, almost 45 million people around the world were suffering from dementia, a spectrum of illnesses that cause a gradual decay in brain function, of which Alzheimer’s is the most common. With life expectancy of patients increasing, researchers believe that this number will rise to 135.5 million by 2050. In the UK, it affects around 800,000 people. Apart from the personal toll of the disease on sufferers and their families, the financial cost to the UK in 2012 was £23bn. Although a great deal of research is underway and scientists are understanding more and more about the condition every year, there is still no effective cure for the disease or therapy to slow memory loss.

Many families have experienced living with someone with Alzheimer’s first hand, and despite speculation that genetics plays an important part in the development of the disease, the biggest risk factor is age; it affects one in six of the over 85s.

At Southampton, researchers in Medicine, Health Sciences and the Centre for Biological Sciences are working through the University’s Institute for Life Sciences (IfLS) to investigate dementia in projects funded by many external sources, including Alzheimer’s Research UK.

Proteins and neuroplasticity

IfLS Research Fellow, Dr Mariana Vargas-Caballero is studying memory loss and how two particular proteins found in excess in the brains of Alzheimer’s patients - amyloid beta and tau protein –interact and interfere with the capacity of cells to store memories.

“People diagnosed with Alzheimer’s may have had the disease for many years before symptoms start to show, so it is important to discover how the malfunction begins at this early stage,” she explains. “Nerve cells have the capacity to strengthen or weaken the connections between them through a function known as synaptic plasticity; this is considered the primary mechanism by which memories are stored in the human brain.”

Mariana is investigating how both amyloid beta and tau protein interact and interfere with synaptic plasticity and has already discovered that amyloid beta does not damage plasticity unless the tau protein is present too. She has been studying the chain of events that may link the proteins with reduced plasticity and has identified that the protein NMDA-GluN2B appears to explain the effects of amyloid beta on these connections.

Understanding memory loss in Alzheimer’s diseaseNeuroscientists at Southampton are playing a key role in the University’s groundbreaking interdisciplinary research into Alzheimer’s disease.


Dr Mariana Vargas-Caballero is investigating how proteins in the brain interfere with cells’ capacity to store memories


Mariana comments: “ NMDA-type proteins are crucial to making new memories and these are responsible for a common phenomenon: ‘brain cells that fire together are wired together.” These proteins are crucial for our brain to build up our knowledge of the world and to store memories of our daily life. However, too much of this kind of activity in the brain can have adverse effects, making brain cells too excitable. Such over activity causes the death of brain cells in diseases such as stroke and advanced Alzheimer’s disease. One of the two approved drugs for Alzheimer’s disease is effective for preventing this over activity in brain cells in the advanced stages of disease. However, Mariana’s research suggests that in the earlier stages of the disease, it is the ‘wiring together’ process that is ineffective. She explains: “ A different drug may be needed when people start losing their memory, or even before, to slow down or stop the chain of events that leads to the death of brain cells.”

The Vargas-Caballero laboratory is using mice specially bred to have amyloid beta in their brains. With PhD student Sarmi Sri, Mariana places them in maze tests, at different stages of the disease, to see whether their normal behaviour is affected or whether they can form new memories. She is also able to test whether the circuits in the mouse brain have been affected. These experiments will help the scientists understand more about how communication and plasticity between nerve cells breaks down when amyloid beta starts to build up.

“We are really interested in whether there is a time window during which nerve cells are particularly vulnerable to damage. Hopefully, our findings will inform new ways to reverse or prevent nerve cell damage in Alzheimer’s, to improve symptoms or slow the disease altogether,” she says. “It is frustrating that, in an age when we are close to finding effective therapies for such diseases as cancer and AIDS, Alzheimer’s is proving so stubborn to researchers.”

It is extremely important that experimental findings in mice can be translated to meaningful discoveries to treat Alzheimer’s in humans. Although brain banks with donated post-mortem tissue are becoming widely available, such tissue does not contain live cells and thus it is impossible to test many facets of their behaviour and function. To address this, the Vargas-Caballero laboratory has teamed up with neurosurgeons Diederik Bulters, Aminul Ahmed and colleagues from the Wessex Neurological Centre. They will use donated small brain tissue samples that would otherwise be discarded after neurosurgery to study how human neurons react to Alzheimer’s disease molecules. Student Chrysia Maria-Pegasiou will carry out an analysis of how the performance of these cells and their capacity to strengthen their connections deteriorates when amyloid beta and/or tau malfunction. This work will be carried out in collaboration with Professor Hugh Perry and the Southampton Research Biorepository (SRB), a biobanking facility provided for all experimental medicine researchers by the University of Southampton’s National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility.

Much multidisciplinary research is underway at the University in the area of Alzheimer’s disease. Dr Delphine Boche, Senior Lecturer in Clinical Neuroscience has led the Alzheimer’s Research UK South Coast Network for the past three years, promoting interdisciplinary work in this area. Early career researchers Dr Diego Gomez-Nicola and Dr Katrin Deinhardt have obtained New Investigator grants from the Medical Research Council and Biotechnology and Biological Sciences Research Council. Diego is examining the factors that influence the progression of brain degenerative disease and has published his research in the Journal of Neuroscience. He is interested in the control of the proliferation of microglial cells as a promising therapeutic approach. He comments: “I am interested in the self-repairing mechanisms of the brain,

looking at how neuronal populations are regenerated in chronic neurodegenerative diseases, as reported in the journal, Brain.” Katrin studies how neuronal function and health are maintained by local and long–range signals inside individual brain cells, and has obtained funding from Alzheimer’s Research UK to analyse what goes wrong with these processes in Alzheimer’s disease. Complementing these approaches, Dr Shmma Quarashie, with senior lecturer Dr Amrit Mudher, has made important insights into the way tau proteins kill neurons, using the fly Drosophila as a research model.

An interesting parallel with the work on Alzheimer’s is research into how the retina of the eye degenerates in diseases associated with old age such as Age-related Macular Degeneration (AMD). Dr Salome Murinello, working under the supervision of senior lecturer Dr Jessica Teeling, has reported similarities in chronic neurodegeneration between Alzheimer’s and AMD, the most common form of blindness in the elderly. This could further inform the way that Alzheimer’s disease progresses in the brain.

Key facts

The Vargas-Caballero laboratory is currently funded by: The Institute for Life Sciences, Alzheimer’s Research UK, The Kerkut Trust, and Alzheimer’s Society.

For more information about the SRB biobank, contact SRB manager Andrew Trousdale on [email protected]


Q What prompted you to enrol for a PhD at Southampton?

My experience of the research environment at Southampton during my undergraduate course persuaded me to pursue a career in research. I was keen to find a PhD in a friendly but academically rigorous environment, and I was also keen to work in a field that was relatively applied. The CASE studentship on offer at Southampton with Bayer Animal Health, to work on new types of drugs to combat parasites, therefore fitted the bill nicely.

Q What did your research involve?

I was researching a new compound with the potential to treat parasitic nematode (round worm) infections. The nematode phylum is diverse, with many thousands of species that become parasites in both animals and plants. They have a high cost in terms of both human and animal health, and are a problem for agriculture. Resistance to these nematicides is continually emerging, leading to a requirement for new compounds. The aim of the project was to determine the mechanism of action of a new class of nematicide known as the cyclooctadepsipeptides. These had been shown to break the resistance, implying a new mechanism of action.

This research was led by Professors Lindy Holden-Dye and Robert Walker with Dr Neil Hopper at Southampton, alongside colleagues at Bayer. I used the microscopic nematode Caenorhabditis elegans so we could fully understand the molecular basis of its resistance-breaking properties.

Q How is a CASE studentship different to a conventional PhD?

These are collaborations between the University and an external partner. I wanted to work in an area of science where my research was closely linked to a practical application (such as developing a drug).

CASE studentships tend to be focused towards these more applied areas of science, reflecting the interests of the industrial partner. They also provide an opportunity to experience science in a commercial environment, offering a placement with the industrial partner.

Q What was the outcome of your work?

Our research supported the licensing of two new veterinary medicines Profender® tablets and Procox® liquid, which are now on sale. The discovery of a drug to counter parasitic worms has influenced international debate concerning the treatment of human infections. The World Health Organization is interested in emodepside as a treatment for neglected tropical diseases such as river blindness. These conditions afflict one sixth of people in the world.

Q What are the benefits of postgraduate study at Southampton?

I had a great experience staying on for postgraduate research at Southampton, and there were many new challenges. Learning new techniques and developing new skills inevitably results in many failed experiments, however in a vibrant group, such as Professor Lindy Holden-Dye’s, there is plenty of assistance available. Enthusiastic postdocs provided me with assistance on many technical problems, and the PhD allowed me to really develop my experimental, presentation and writing skills thanks to the support from supervisors. Postgraduate study at Southampton provided me with a fantastic learning environment that encouraged me to develop a range of skills that now support me in my current job.

Q What are you doing now?

I am currently working in research at Syngenta, an agritech company. I work in the area of crop protection research

developing new insecticides, where there is a continual need to develop new products. This is partly to control resistance but also to comply with changes in the regulations for use.

Key to the development and licensing of new insecticides is an understanding of their mechanism of action. I use many of the same techniques and skills that I developed at Southampton, exploiting the model organism C. elegans. In addition to this, we need to understand a range of other factors including metabolism, uptake, toxicity, spectrum and resistance mechanisms. Working at Syngenta, I have been able to contribute to our understanding of many of these factors in a range of projects. This has enabled me to get a broader view of the science behind the development of an insecticide product.

In order to be competitive, Syngenta needs to be at the cutting–edge of biotech. We are therefore continually reviewing literature and putting into practice new approaches that can assist in the development of crop protection products. Work at Syngenta differs from academia in that the focus of research can quickly change as we need to respond to commercial pressures. This can sometimes be a frustration, but it has the benefit of enabling you to work in a wide range of areas.

There is a vibrant scientific community at Syngenta which provides an interesting and motivating environment in which to work. From my experience of working in industry, I would recommend it to others. Starting with the skills acquired during a PhD is certainly beneficial and I would recommend this route into industrial science.

For all postgraduate opportunities available through the Centre for Biological Sciences visit www.southampton.ac.uk/biosci/postgraduate

Groundbreaking veterinary drugs Dr Marcus Guest, a geneticist at Syngenta Crop Protection discusses the development of new veterinary drugs, which resulted from his PhD research at Southampton.


http://www.southampton.ac.uk/biosci/postgraduate

In brief

Extending the shelf life of packaged salad

Professor Gail Taylor and her team have helped to produce salads with a longer shelf life. They worked with Vitacress, one of the biggest producers of packaged salads, to understand what keeps salad leaves fresh for longer. Their results are now being used by the company.

“Developing high quality, nutritious, sustainable salad leaves is really important for Vitacress,” Gail explains. “They need science to achieve that, and our research has directly impacted on the business.”

The researchers used funding from an Industrial Partnership Award (IPA) from the Biotechnology and Biological Sciences Research Council (BBSRC) to study the genetics of processable salad leaves.

Firstly, they identified what it was about certain salad leaves that gave them a longer shelf life. They found that smaller, tougher leaves, with lots of small cells packed closely together, lasted longer. They then worked out which regions of the lettuce genome were responsible for these desirable characteristics.

As a result of this research, the scientists have initiated a programme in which crop breeders are selectively breeding plants with the genetic material responsible for leaves with a longer shelf life. During the project, the researchers also made the unexpected discovery that using less water when growing salad also improves its shelf life, which has added environmental benefits.


Saving Tasmanian devils from cancerA rare contagious cancer that has almost wiped out Tasmanian devils on their island could help researchers better understand the human form of the disease.

Biological scientist Dr Hannah Siddle has moved to Southampton from the University of Cambridge to establish her own research lab to study the condition; she also values the interdisciplinary approach to research of the University’s Institute for Life Sciences (IfLS).

“A wildlife photographer saw the first devil with a facial tumour in Tasmania in 1996. The cancer spread quickly and only the animals in the north west of the island are still free from the disease,” she explains. “Conservationists are trying to save the devils from extinction in the wild, but they need to know how the cancer cells move between the animals and how it can be cured.”

Hannah started working on the problem following her PhD at the University of Sydney in evolutionary genomics on wallabies. In devils, cells affected by the cancer have lost a layer of MHC molecules, which enable the immune system to recognise external threats and cancer cells. However, the genes that control these molecules are still there and can function. Hannah is hopeful a vaccine can be developed to ‘turn on’ these MHC molecules to both protect Tasmania’s remaining devils and help in the fight against human cancers.

Capturing images of fossilised single-celled organismsEvolutionary ecologist Dr Thomas Ezard is using the University’s new Carl Zeiss - XRadia X-ray microscope to secure images of tiny aquatic creatures, no larger than grains of sand, which could help us understand more about how ecology shapes evolution.

The £500,000 equipment housed in the µ-VIS X-ray Imaging Centre has helped Thomas examine fossils of the planktonic foraminifera down to a size of 1.02 microns. They are found in large quantities in all the world’s oceans and can be dated precisely to when their shells form sediment.

“Thanks to the advanced imaging equipment, we can better understand the developmental life history of these creatures and how they responded within their lives to changing climate conditions millions of years ago,” he says. “We can therefore get a better understanding of how ecology shapes the formation of new species.”

Thomas, who has an Advanced Fellowship from the Natural and Environmental Research Council (NERC), works with colleagues in Ocean and Earth Science at the National Oceanography Centre Southampton, as well as the Institute for Life Sciences.

Pioneering research in cystic fibrosisDr Jeremy Webb has been awarded £250,000 to continue his work into understanding the causes of disease in cystic fibrosis (CF) patients. The grant from the National Institute for Health Research (NIHR) will investigate how lungs in CF patients are affected by biofilms; viscous layers of sticky bacteria which are resistant to antibiotics and difficult to remove.

The two year national study, with Dr Gary Connett and Professor Saul Faust from the University Hospital Southampton NHS Foundation Trust, will analyse up to 200 samples of biofilm from around the country.

“This research is important because we know very little about how long-term infection by biofilms in the lungs affects the progression of disease in CF patients,” explains Jeremy. “If we can understand it better, we can go on to develop treatments that target biofilms much more effectively.”

Jeremy, with colleagues at the University of New South Wales in Sydney, Australia, has already found that nitric oxide can break up biofilm in lungs; they have secured a full patent for this discovery and clinical trials are underway in Southampton as part of the University’s ‘bench to bedside’ research programme.

The University of Southampton, in partnership with Imperial College London, has also secured a £750,000 grant from the CF Trust to establish a Strategic Centre of Excellence for research into the disease.


Funding for research on body clocks and their biological impact Biological scientist Dr Herman Wijnen has been awarded two new grants to investigate how animals keep time on a daily basis. Approximately £385,000 has been awarded by the Biotechnology and Biological Sciences Research Council (BBSRC) to study the way that the fruit fly Drosophila melanogaster synchronises its body clock to daily environmental temperature cycles.

“This research could provide valuable insights in the way that the behaviour and life cycle of harmful insects, such as agricultural pests and disease vectors, is governed by temperature,” he says. “What’s more, the body clocks of flies and humans are connected to temperature response mechanisms by very similar regulatory molecules. So, we may even learn something about the way that our own body temperature rhythms are used as daily time cues.”

A €100,000 European Union Marie Curie Career Integration Grant will allow a new PhD researcher to follow up on studies of sleep/wake behaviour by current Southampton postgraduate researcher, Karolina Mirowska. Together with other members of Herman’s laboratory, Karolina discovered a developmental role in flies for one of the molecular clock components that is also found in humans. “The goal is to find out how this component acts in the developing brain to set up adult sleep/wake rhythms”, adds Herman.

Gift helps biological science students gain first hand experience of research A biological sciences graduate has generously funded a vacation scholarship for undergraduates to carry out their own practical research project in the University laboratories.

Dr Sarah Caddick, who studied for a PhD with Dr John Chad and graduated in 1993, is now the Neuroscience Advisor to Lord Sainsbury of Turville and the Gatsby Charitable Foundation. She returned to Southampton to meet biomedical sciences student Tom Gleeson, who was awarded the competitive scholarship in 2013. He says: “I enjoyed working alongside postgraduate researchers in the laboratory and it has motivated me to continue in research by studying for a doctorate”. During the summer, Tom worked with supervisor Dr Herman Wijnen and PhD student Karolina Mirowska on a project using the genetic animal Drosophila melanogaster, the fruit fly, as a model system to investigate sleep disruption in Alzheimer’s disease. He has obtained interesting preliminary data suggesting that a protein implicated in neurodegeneration affects the ‘clock’ neurons in the fly.

Sarah’s gift has resulted in the creation of the John W Caddick Neuroscience Scholarship in memory of her father. She says: “I wanted to make the donation to support scientific education and help inspire the next generation of neuroscientists. It is very rewarding for alumni to keep in touch with the University and make a difference for today’s students.”

Looking at molecules inside living cellsJohn Chad, Professor of Neuroscience, is working with colleagues at the Optoelectronics Research Centre (ORC) to develop pioneering microscopic techniques to image activity within living cells at the nanoscale. He hopes this will help him understand how the brain cells can assemble themselves.

Existing optical imaging technology has wavelength-limited resolution that is much coarser than needed to image individual component molecules. This latest research with Dr Ed Rogers at the ORC at Southampton can spatially confine light to a size well below the wavelength, producing much finer resolution. Experiments have already proven the technique works with materials such as metals and ceramics, the next stage is to adapt and speed up the process to capture movement inside living cells.

“This has the potential to help biological scientists understand much more about life at a molecular level,” explains John. “It will be more difficult to produce high resolution images of molecules within living organisms but it is well worth persevering with the challenge.”

This interdisciplinary research has been funded by a transitional grant from the Engineering and Physical Sciences Research Council (EPSRC) under the auspices of the University of Southampton’s Institute for Life Sciences (IfLS) in collaboration with Dr Joanne Bailey, Dr Tracey Newman and Professor Peter Smith.

In brief


New advances in treatment mean most women who develop cancer now survive the disease. However, conventional radiotherapy and chemotherapy can leave patients infertile by damaging eggs in the ovary. Professor Keith Jones has been awarded a grant by the Biotechnology and Biological Sciences Research Council to understand how eggs respond to this attack on their DNA and why some are able to repair themselves.

“This basic research into eggs’ cell biology is essential because attempts so far to freeze eggs before treatment and revive them afterwards have not been very successful,” says Keith. “Our eventual aim is to enable women to embark on cancer treatment knowing that their levels of fertility will not be damaged by it.”

Most of the eggs in the ovary are in a very early stage of development and are quickly killed by radiation of drugs involved in cancer treatment. It is the eggs that are reaching maturity and capable of being fertilised that Keith and his five-strong team at the Centre for Biological Sciences are examining.

Curing cancer while preserving fertility


J. Dillon, I. Andrianakis, R. Mould, B. Lent, W. Liu, C. James, V. O’Connor, L. Holden-DyeDistinct molecular targets including SLO-1 and gap junctions are engaged across a continuum of ethanol concentrations in Caenorhabditis elegansThe FASEB Journal 2013 Vol. 27 PP. 4266-4278

C. Hu, J.Dillon, J. Kearn, C. Murray, V. O’Connor, L. Holden-Dye, H. MorganNeuroChip: a microfluidic electrophysiological device for genetic and chemical biology screening of Caenorhabditis elegans adult and larvaePLoS One 2013 Vol. 8 PP. e64297

H.L. Hsieh, H. OkamotoMolecular interaction of jasmonate and phytochrome A signallingJournal of Experimental Botany 2014 Vol. 65 PP. 2847-2857

H. Okamoto, M. FutaiVacuolar-type ATPases in animal and plant cellsEncyclopedia of Biophysics 2013 PP. 2719-2724

C.P. Doncaster, A. Jackson, R.A. WatsonCompetitive environments sustain costly altruism with negligible assortment of interactionsScientific Reports 2013 Vol. 3 PP. 1-6

C.P Doncaster, A. Jackson, R.A. WatsonManipulated into giving: when parasitism drives apparent or incidental altruismProceedings of The Royal Society B. Biological Sciences 2013 Vol. 280

P.K. Menguer, E. Farthing, K.A. Peaston, F.K. Ricachenevsky, J.P. Fett, L.E. WilliamsFunctional analysis of the rice vacuolar zinc transporter OsMTP1Journal of Experimental Botany 2013 Vol. 64 PP. 2871-2883

F.K. Ricachenevsky, P.K Menguer, R.A. Sperotto, L.E. Williams, J.P. FettRoles of plant metal tolerance proteins (MTP) in metal storage and potential use in biofortification strategiesFrontiers in Plant Science 2013 Vol. 4

D. Gómez-Nicola, N.L. Fransen, S. Suzzi, V.H. PerryRegulation of microglial proliferation during chronic neurodegenerationThe Journal of Neuroscience 2013 Vol. 33 PP. 2481-2493

D. Gomez-Nicola, J. Teeling, C. Guaza, J.P. Godbout, D.D. TaubThe role of inflammatory mediators in immune-to-brain communication during health and diseaseMediators of Inflammation 2013 Vol. 2013 PP. 1-3

A. Anastasia, K. Deinhardt, M.V. Chao, N.E. Will, K. Irmady, F.S. Lee, B.L. Hempstead, C. BrackenThe Val66Met Polymorphism Alters the BDNF Prodomain Structure to Induce Neuronal Growth Cone RetractionNature Communications 2013 Vol. 4

H. Bowling, G. Zhang, A. Bhattacharya, L.M. Pérez-Cuesta, K. Deinhardt, C.A. Hoeffer, T.A. Neubert, W.B. Gan, E. Klann, M.V. ChaoAntipsychotics Activate mTORC1-Dependent Translation to Enhance Neuronal Morphological ComplexityScience Signaling 2014 Vol. 7 PP. ra4

E. Miranda, I.K. Nordgren, A.L. Male, C.E. Lawrence, F. Hoakwie, F. Cuda, W. Court, K.R. Fox, P.A. Townsend, P.K. Packham, S.A. Eccles, A. Tavassoli

Cyclic peptide inhibitor of HIF 1 heterodimerization that inhibits hypoxia signaling in cancer cellsJournal of the American Chemical Society 2013 Vol. 135 PP. 10418-10425

K.M. Rahman, P.J.M. Jackson, C.H. James, B.P. Basu, J.A. Hartley, M. de la Fuente, A. Schatzlein, M. Robson, R.B. Pedley, C. Pepper, K.R. Fox, P. Howard, D.E. ThurstonGC-Targeted C8-linked pyrrolobenzodiazepine-biaryl conjugates with femtomolar in vitro cytotoxicity and in vivo antitumor activity in mouse modelsJ Journal of Medicinal Chemistry 2013 Vol. 56 PP. 2911-2935

Journal papers published from January 2013 – June 2014This sample of journal papers indicates the breadth of research in Southampton’s Centre for Biological Sciences. For more research papers, please view individual staff profiles online.


M.J. Tallis, E. Casella, P.A. Henshall, M.J. Aylott, T.J. Randle, J.I.L. Morison, G. TaylorDevelopment and evaluation of ForestGrowth-SRC a process-based model for short rotation coppice yield and spatial supply reveals poplar uses water more efficiently than willowGCB Bioenergy 2013 Vol. 5 PP. 53-66

T. H. G. Ezard, G.H. Thomas, A. PurvisInclusion of a near-complete fossil record reveals speciation-related molecular evolutionMethods in Ecology and Evolution 2013 Vol. 4 PP. 745-753

S. Townley, T.H.G. EzardA G matrix analogue to capture the cumulative effects of non-genetic inheritanceJournal of Evolutionary Biology Vol. 26 PP. 1234-1243

P.J.S. Smith, I. Davis, C.G. Galbraith, A. StemmerSpecial issue on high-resolution optical imagingJournal of Optics 2013 Vol. 15 PP. 1-3

S. Vang, H.T Wu, A. Fischer, D.H. Miller, S. MacLaughlan, E. Douglass, M. Steinhoff, C. Collins, P. J. S. Smith, L. Brard, A.S. BrodskyIdentification of Ovarian Cancer Metastatic miRNAsPLoS ONE 2013 Vol. 8

J. Gibson, R.D. Gilbert, D.J. Bunyan, E.M. Angus, D.J. Fowler, S. EnnisExome analysis resolves differential diagnosis of familial kidney disease and uncovers a potential confounding variantGenetics Research 2013 Vol. 95 PP. 165-173

J. Gibson, W. Tapper, S. Ennis, A. CollinsExome-based linkage disequilibrium maps of individual genes: functional clustering and relationship to diseaseHuman Genetics 2013 Vol. 132 PP. 233-243

S.I.R. Lane, K.Y. Jones Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytesNature Communications, 5, 3444

D. Gómez-Nicola, N.L. Fransen, S. Suzzi, V.H. PerryRegulation of microglial proliferation during chronic neurodegenerationThe Journal of Neuroscience 2013 Vol. 33 PP. 2481-2493

V.H. Perry, J. Teeling Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegenerationSeminars in Immunopathology 2013 Vol. 35 PP. 601-612

H.V. Siddle, A. Kreiss, C. Tovar, C.K. Yuen, Y. Cheng, K. Belov, K. Swift, A.M. Pearse, R. Hamede, M.E. Jones, K. Skjødt, G.M. Woods and J. KaufmanReversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancerProceedings of the National Academy of Science USA 2013 Vol. 110 PP. 5103-5108

H.V. Siddle, J. KaufmanA tale of two tumours: Comparison of the immune escape strategies of contagious cancersMolecular Immunology 2012 Vol. 55 PP. 190-193

M.A. Chapman, S.J. Hiscock, D.A. FilatovGenomic divergence during speciation driven by adaptation to altitudeMolecular Biology and Evolution 2013 Vol. 30 PP. 2553-2567

M.A. Chapman, J.R Mandel, J.M. BurkeSequence validation of candidates for selectively important genes in sunflower PLoS ONE 2013 Vol. 8 PP. e71941


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Biological Sciences New Boundaries 2014

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