Researchers to tackle key questions about health and disease with major Wellcome Trust grants

Four Imperial scientists are among the first recipients of the Wellcome Trust’s new Investigator Awards - News

by Sam Wong
Friday 10 June 2011 

Four Imperial scientists are among the first recipients of the Wellcome Trust’s new Investigator Awards - major long-term grants given to outstanding researchers addressing the most important questions about health and disease announced this month.

Professors Kenneth Harris, Sara Rankin, David Holden and Gavin Screaton are among 27 researchers to receive the inaugural awards, which range from around £1 million to £3 million. They are looking for new ways to fight dengue fever, exploring how the brain processes information, how drugs could mobilise stem cells and how bacteria survive in human cells.

Sir Mark Walport, Director of the Wellcome Trust, says: "The Wellcome Trust Investigators, together with our existing Fellowship holders, represent some of the very brightest minds in biomedical science. They are seeking answers to challenging research questions that could potentially transform our understanding of the mechanisms of health and disease.

"We are demonstrating our confidence in these outstanding individuals by providing longer-term, flexible funding; in return, we expect that they will make significant advances in knowledge in their field and act as ambassadors within the research community, helping us achieve our aim of improving human and animal health."

Investigator Awards provide funding for scientists with an excellent track record and in an established post. The awards are designed to offer the flexibility and time to enable them to tackle important research questions.

Battling bacteria

Professor David Holden

Professor David Holden, from the Department of Medicine, will use his Investigator Award to understand the mechanisms that enable two important bacterial pathogens - Salmonella enterica and Streptococcus pyogenes - to survive and persist within mammalian cells.

Different strains of Salmonella cause typhoid fever, of which there are over 21 million cases worldwide each year, and diarrhoeal disease. Streptococcus causes several important diseases in humans, including throat and skin infections, as well as more severe invasive diseases, such as streptococcal toxic shock syndrome and necrotising fasciitis. Streptococci probably cause more deaths per year globally than TB or malaria, but are greatly under-researched by comparison.

Both Salmonella and Streptococcus have the capacity to avoid or withstand attack by their host’s immune system, enabling them to survive inside human cells, and to enter a longer term persistent state in which they are insensitive to antibiotic treatments.

“We will use a variety of molecular genetic and cell biological techniques to identify the genetic basis of these phenomena and carry out mechanistic studies to understand how the encoded proteins enable bacterial survival and persistence in host cells,” Professor Holden said. “Knowledge gained from these studies could be used in the future to help in the design of next-generation vaccines and novel antibiotics.”

Mobilising the body’s repair kit

Professor Sara Rankin

Professor Sara Rankin’s research in the National Heart and Lung Institute aims to develop innovative regenerative medicines that mobilise stem cells from the bone marrow.

Adult bone marrow contains mesenchymal stem cells that are known to help promote tissue repair. Stem cell therapies have been developed using these mesenchymal stem cells, which involve extracting these cells from the bone marrow and multiplying them in the lab, before injecting them back them back into the body. However, this type of stem cell therapy is expensive and is associated with a number of regulatory, practical and technical hurdles. Professor Rankin has developed a way to mobilise the cells from the bone marrow into the blood. This innovative approach is more cost-effective and overcomes many of the difficulties that have held back stem cell therapy.

With funding from the Investigator Award, Professor Rankin plans to study further the molecular mechanisms involved in mobilising the stem cells, the characteristics of mobilised stem cells and how ageing might affect the process.

“My work is aimed at developing therapies for mobilising mesenchymal stem cells, which may have a wide range of clinical applications, including heart disease, orthopaedic injuries and autoimmune diseases,” Professor Rankin said. “This award will lead to an in-depth understanding of the mobilisation process at the molecular, cellular and tissue level that is vital for the development of safer, more effective therapies.”

Unlocking the brain

Professor Kenneth Harris

Professor Kenneth Harris, from the Department of Bioengineering, has a joint award with Professor Matteo Carandini at University College London to investigate how circuits in the brain integrate information from the sense organs with signals from within the brain.

Dedicated centres in the brain process inputs from the eyes and ears. However, little is known about how groups of neurons in these areas integrate multiple sensory inputs into a coherent pattern, and how brain activity driven by the senses interacts with internal patterns of activity from within the brain. This non-sensory activity could be providing the context that we use to interpret sensory signals and act on them.

Professor Harris and his collaborators aim to improve our understanding of how circuits in the brain integrate external and internal signals. To do this they will record electrical activity in the brains of mice as they move through a virtual reality world in an air-suspended ball.

“We think that information-processing circuits in the brain are functioning abnormally in diseases such as schizophrenia, but currently we know very little about how these circuits operate in the healthy brain,” Professor Harris said. “With this grant, we’re looking to uncover fundamental laws that predict how circuits in the brain react to sensory inputs depending on the internal state of the brain. Once we have a better understanding of how the brain works normally, we can then start to look at what might be going wrong in conditions like schizophrenia.”

Fighting dengue fever

Professor Gavin Screaton

Professor Gavin Screaton’s research in the Department of Medicine aims to gain a better understanding of the pathology and immunology of dengue fever, to help inform the design of new treatments and vaccines.

The dengue virus is endemic in many parts of the world, especially in southeast Asia and the western Pacific. The World Health Organisation estimates that a fifth of the world’s population is at risk, with around 50 million infections each year. One in 20 cases leads to severe leakage from the circulatory system, which can result in shock, haemorrhage, and in rare cases can be fatal. Currently there are no drugs or vaccines available to combat the disease.

Scientists know very little about why some people suffer severe illness while others can be infected without showing any symptoms. Professor Screaton and his collaborators will look to discover more about dengue and the body’s response to infection more generally.

“Over a number of years, our lab has formed important collaborations to allow us access to clinical material, and developed a range of skills needed to study dengue on a broad front,” Professor Screaton said. “The laboratory is now uniquely poised to take the first steps in translating our early findings with the virus into new treatments.

“Stable funding, although not a prerequisite for successful science, is a very significant enabler. We plan to carry out a broad series of experiments to tackle dengue disease, some of which are high risk and some of which will take a number of years to bear fruit. As with all good science, surprises will occur, opening up exciting new areas to explore. The long term and generous support from an Investigator Award will allow me to pursue these without the distraction of having to continuously seek piecemeal funding.”