Translational Medicine: Recent Episodes
Oxford University
Research in Medicine needs to ultimately translate into better treatment of patients. Researchers at the Nuffield Department of Medicine, University of Oxford, collaborate to develop better care and improved preventive measures. Findings in the laboratory are translated into changes in clinical practice, from Bench to Bedside.
Dr Janjira Thaipadungpanit from our MORU unit in Bangkok, Thailand, tells us about her research on molecular diagnosis and bacterial genotyping A molecular microbiologist, Dr Janjira’s research focusses on using bacterial typing based on genome to confirm which disease is present in a patient. She aims to develop a single whole genome sequence type test using mutliple-PCR assays that can determine from a single sample of blood what bacteria or viruses are present in a patient’s blood – thereby speeding up diagnosis and potentially saving lives in resource-limited settings. Head of Molecular Microbiology at MORU, Dr Janjira Thaipadungpanit’s research interests include the molecular epidemiology of leptospirosis and melioidosis using multilocus sequence typing or genome data and molecular diagnosis to identify the causes of acute febrile illness and sepsis in patients.
Dr Markus Winterbert from our MORU unit in Bangkok, Thailand, tells us about his research on biomarkers for tropical diseases Having a background in malaria physiology and biochemistry, Markus Winterberg’s research focus is on the interaction between host, pathogen and drug, the metabolism of antimalarial drugs and discovering biomarkers for tropical diseases. Markus aims to use these biomarkers to develop non-invasive, field-based rapid diagnostic tests for tropical diseases that quickly identify pathogens, thereby improving diagnostics and the treatment of patients. Dr Markus Winterberg is Head of Laboratory and a Principal Investigator in MORU’s Department of Clinical Pharmacology. The key aspect of his research is ‘trop-med-omics’, the application of mass spectrometry-based bioanalysis in tropical medicine, particularly using proteomics and metabolomics to identify a disease in a patient.
Premjit Amornchai from our MORU unit in Bangkok, Thailand, tells us about her work as biosafety level 3 lab manager and microbioogy safety officer To prevent relapse or reinfection, melioidosis requires a specific and prolonged treatment. Melioidosis is endemic at least 45 countries, but greatly under-reported, with a microbiological culture required to confirm diagnosis. This can take 2-7 days. In Thailand, up to 40 percent of hospital admitted melioidosis patients die. Premjit works with MORU researchers who have produced a rapid diagnostic test that aims to improve both diagnosis and public awareness of melioidosis. Microbiologist Premjit Amornchai heads MORU’s Bio-Safety Level (BSL) 3 Laboratory in Bangkok, Thailand. Safety is very important for Premjit. The BSL3 Lab handles several dangerous materials, most notably, Burkholderia pseudomallei, a highly pathogenic bacterium commonly found in soil and water in Southeast Asia and northern Australia. The pathogen causes the difficult to diagnose, deadly bacterial infection melioidosis.
Professor Bob Snow from our KEMRI-Wellcome programme in Nairobi, Kenya, tells us how his research brings together epidemiological profiles and government policies to maximise malaria control programmes in Africa Quality data is vital to design better malaria control programmes. This project helps various African countries gather epidemiological evidence to better control malaria. Professor Bob Snow showed how sub-regional, evidence-based platforms can effectively change malaria treatment policies. Professor Bob Snow has developed a large programme of work on the phenotype of malaria disease, its relationship to parasite exposure and its wider public health burden. Technical advisor to the Kenyan Government (and member of a number of international malaria advisory panels), Professor Snow provides the bridge between basic malaria epidemiology and malaria control policy in the region. Malaria control in Africa.
Dr Lorenz von Seidlein from our MORU unit in Bangkok, Thailand, tells us about his research on malaria elimination in the Greater Mekong sub-region Multidrug resistant P. falciparum malaria is now established in parts of Thailand, Laos and Cambodia, causing high treatment failure rates for artemisinin combination therapies, the main falciparum malaria medicines. A further spread from Myanmar to India then sub-Saharan Africa would be a global public health disaster. TME seeks the best ways to eliminate drug-resistant malaria, using both technical solutions and novel ways that engage entire communities. Dr Lorenz von Seidlein coordinates MORU’s Targeted Malaria Elimination (TME) study, which seeks to eliminate artemisinin resistant falciparum malaria by treating entire communities that have significant levels of subclinical malaria parasite infections and transmission with the antimalarial Dihydroartemisinin-piperaquine (DHA-PIP).
Professor Derrick Crook from our Experimental Medicine division tells us about his research on tracking infections Professor Derrick Crook's research consortium focusses on translating new molecular technologies and advances in informatics into the investigation of microbial transmission, diagnosis of infectious disease and identifying outbreaks of communicable disease. This research aims to translate deep sequencing of pathogens on an epidemiological scale for tracking infections, and is focussed on four different major pathogens: Staphylococcus aureus (including MRSA), Clostridium difficile, Norovirus and Mycobacterium tuberculosis. Understanding how an infection spreads is vitally important for prevention. Whole genome sequencing of microorganisms allows us to construct family trees of infections, from donnor to recipients, and understand how microbes behave in general. Through its genetic code, we can also predict whether a germ is susceptible or resistant to a specific antibiotic, and give patients a more stratified and personalised treatment.
Dr Olga Tosas-Auguet from our unit in Kenya tells us about her research on mapping bacterial antibiotic resistance Dr Olga Tosas-Auguet aims to develop ad evaluate a new approach to large scale surveillance of bacterial antibiotic resistance in low income settings. This approach can then be taken forward to a testing stage, initially in partnership with an emerging network of policy makers and healthcare practitioners in Africa. Resistance to antibiotics is a growing issue worldwide. Mapping where the resistance is as well as its distribution and diversity is hampered by the lack of laboratory facilities in many parts of the world. New technologies allow the characterisation of whole pathogen communities, giving us clues where multi-drug resistant organisms come from. This can help set up a better public health perspective surveillance.
David Dance from our LOMWRU unit in Laos tells us about his research on bacterial infections in Laos, particularly melioidosis David Dance is a Clinical Microbiologist supporting the work of LOMWRU (Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit) on bacterial infections of importance to public health in Laos. He is particularly interested in all aspects of melioidosis (Burkholderia pseudomallei) infection, especially gaining a greater understanding of the global distribution of the disease and the environmental factors that underpin its distribution. Laos is seing a growing number of melioidosis, a bacterial infection caused by a bacterium that lived in the environment. Meliolidosis is a disease greatly under-recognised and treatment is specific, making it a major threat to farmers in developing countries. A better understanding of the prevalence of this infection and how it spreads allows us to better target prevention and treatment.
Dr Georgina Humphreys coordinates the WorldWide Antimalarial Resistance Network (WWARN) study groups by encouraging partner engagement and managing the data curation and development of publications. WWARN is a network of research that analyses pooled data of numerous clinical trials. The sheer size of those data sets allows study groups to answer questions that couldn't be asked of a normal size clinical trial, such as the efficacy of an anti-malarial drug on malnourished or severely anaemic children. This research helps design policies to maintain the efficacy of current anti-malaria drugs, currently threatened by growing resistance.
Dr Gail Carson is Head of ISARIC Coordinating Centre (International Severe Acute Respiratory and Emerging Infection Consortium), a network of networks established in 2011 to ensure a rapid research response to outbreaks of pandemic potential. A quick and efficient response to an outbreak requires strong central communication and coordination. Information needs to be shared quickly and then fed into patient care and policy. A wider approach, cutting across disciplines and specialities, helps limit the number of infected people and the impact on the economy.
Professor Skirmantas Kriaucionis aims to to elucidate the molecular function of DNA modifications in normal cells and cancer. Although all cells in our body have the same genome, they look different and perform different functions. Epigenetic modifications such as methylations ensure which sets of genes are expressed in specific cells and how this specificity is inherited. Cancer cells show particular epigenetic abnormalities which can be targeted for cancer therapies.
Professor Frank Smithuis is the director of MOCRU, Myanmar Oxford Clinical Research Unit. MOCRU involves a network of 6 clinics and 650 community health workers in remote areas. Up until now, Myanmar has spent little on heathcare and receive little assistance from rich countries. Prevention is difficult, which leaves diagnosis and treatment. MOCRU has set up a network of community health workers, trained and supplied with diagnostics and treatments, to help improve access to healthcare for remote communities.
Housed within the Target Discovery Institute, the Alzheimer’s Research UK Oxford Drug Discovery Institute (ODDI) juxtaposes drug discovery expertise alongside scientific and academic understanding of patients, disease mechanisms and model systems. The burden caused by Alzheimer’s disease and other dementias represents one of the biggest problems for our healthcare systems. The last medicine was approved in 2002 and today we only have symptomatic treatments. ARUK-ODDI brings together chemists, biologist, psychiatrists and neuroscientists, many of them with pharmaceutical background, aiming to accelerate the discovery of novel and effective treatments.
Dr Claire Palles studies whole genome sequencing data and targeted analyses with the aim of discovering genetic variants that affect susceptibility to colorectal cancer and Barrett’s oesophagus. The gastrointestinal track is responsible for more cancers than any other system. A condition called Barrett's oesophagus, characterised by a change in the cells lining the oesophagus, can lead to oesophageal adenocarcinoma. Only few people with Barrett's oesophagus will go on to develop cancer, and genome sequencing studies aim to identify genetic risk factors and therefore better target high-risk patients.
LOMWRU researchers conduct clinical research to help improve global, regional and Lao public health. They focus on infectious diseases, and also investigate diseases of nutrition and poverty. Poor quality medicines are a serious threat to our health. Falsified medicines and substandards medicines are a problem for all countries, but particularly for low and middle income countries where we see, for example, a large epidemic of fake anti-malarial drugs. Globally, better medicine regulatory authorities will help improve the quality of our medicines.
Director of OUCRU-Nepal, Dr Buddha Basnyat studies high altitude illness as well as undifferentiated febrile illness in the tropics, both common but neglected problems in Nepal. High altitude illness can be prevented by a simple rule: don't go too high, too fast. Drugs can also be used, and Dr Basnyat showed that a much lower dose of Diamox, a commonly used drug, is as effective. His research also focusses on the effect of high altitude on pilgrims, an older, poorer and more vulnerable population.
Professor Kevin Baird leads our Eijkman-Oxford Clinical Research Unit (EOCRU) in Jakarta, Indonesia. Delivering health care in Indonesia is a challenge, made more difficult by the geography and distances. Our EOCRU unit specialises in clinical trials on tropical infections, particularly Plasmodium vivax malaria. Current treatments with primaquine are effective but very toxic for patients with G6PD deficiency. Better point of care diagnostics can help us treat all patients safely.
Dr Mehul Dhorda heads the Asia Regional Centre of the WorldWide Antimalarial Resistance Network (WWARN). Artemisinin resistance is firmly established in many parts of Southeast Asia and threatens the lives of millions of people. To improve regional intelligence and aid containment efforts, Dr Dhorda promotes the collection of high quality data on malaria drug resistance. His research aims to simplify and harmonise data, securely store results and analyse comparative or collective pooled analyses.
Professor Peter Simmonds studies the epidemiology, evolution and emergence of a wide range of human pathogenic viruses. RNA viruses are major pathogens that represent the majority of new viruses emerging over time. They are particularly good at evading the host's response to infection. A better understanding of the interaction between virus and host can lead to a better control of viral infections. Recent discoveries on viral genome composition and structure might allow us to manipulate this interaction and generate new, safer vaccines.
Professor Frank von Delft works to ensure that X-ray structures can serve as a routine and predictive tool for generating novel chemistry for targeting proteins. In the process of drug discovery, X-ray crystallography is the most sensitive way to find out which compounds bind to a target protein. Recent advances in technology allow researchers to test many more compounds, much more rapidly. The ultimate aim is to bring much needed new treatments to patients.
Professor Ben Cooper from MORU in Thailand uses mathematical modelling and statistical techniques to help understand the dynamics of infectious disease and evaluate potential control measures. Antibiotic resistance is one of today's major global health problems. Mathematical models help us answer what if questions and evaluate the impact of specific interventions such as hands hygiene on the spread of bacterial drug resistance. Effective solutions are then translated into policy changes or changes in practice at national or international level.
Dr Richard Maude's work combines clinical studies, descriptive epidemiology and mathematical modelling of malaria in South and Southeast Asia. Malaria epidemiology focuses on two main challenges to malaria elimination: antimalarial drug resistance and the movement of people that are spreading the malaria parasite. Travel surveys and cellphone records, combined with population parasite genetics help predict the spread of malaria and of drug resistance. Close coordination with all groups and agencies involved is crucial to malaria surveillance and elimination strategies.
Naomi’s work focuses on supporting researchers to collect, clean and store research data. PRESERVING EVIDENCE FOR THE FUTURE Research is only as good as the evidence it generates, and data management is a critical part of this process since it supports findings. High quality data must be preserved for long term use and available to the research community. Ultimately, data is not about numbers, but about people's lives and health.
Dr Kesinee Chotivanich's laboratory provides facilities and resources to researchers, students, and collaborators who are interested in tropical diseases, with the aim to improve patients’ care. More effective diagnosis and treatments are needed to reduce the morbidity and mortality affecting malaria patients. Researchers at the Malaria Laboratory at MORU study the pathophysiology of the disease, and test new compound drugs for anti-malarial activity. In the context of growing artemisinin resistance, this research will have a global impact.
Dr Brian Marsden aims to make structural and chemical biology data accessible to non-experts, by providing computational resources including data management, sample tracking, in silico modelling support plus provision of public access to SGC data. Protein structures are powerful tools in the development of medical drugs, but they are not very accessible to non-specialists. Research informatics presents these structures more simply and interactively, and helps scientists make decisions. This will hopefully accelerate the development of new medicines.
Dr Ross Chapman studies the molecular events triggered by DNA damage detection, and why defects in these events lead to immune deficiency and cancer in humans. GENOME INTEGRITY
Whilst controlled DNA breaks allow for our vast repertoire of antibodies, DNA damage happening out of context can lead to cancer or predisposition to cancer. Recent developments in personalised medicine exploit the DNA repair weaknesses of cancer cells to selectively kill them. A better understanding of the underlying mechanisms can help develop innovative and targeted therapies.
There is a great need for better treatments for malaria and for a preventative malaria vaccine. SPACIAL EPIDEMIOLOGY & VACCINES
Understanding the variation of malaria risk between houses, villages or region, and how malaria is transmitted in and around that variability helps develop better malaria control programmes and use their resources more wisely. Since malaria control tools are becoming less effective with time, progress in vaccine design is essential.
The Cambodia Oxford Medical Research Unit (COMRU) is based in Siem Reap, northern Cambodia, which remains one of the poorest countries in South East Asia with extremely limited health services. PNEUMONIA IN CAMBODIA
Infectious diseases are prevalent in Cambodia, a country that is struggling with poor infrastructure. Streptococcus pneumoniae causes the most severe form of pneumonia and is now targeted by the pneumococcal conjugate vaccine. Dr Paul Turner is studying the effect of this vaccine in field conditions in SE Asia, as well as other direct applications such as the evaluation of a new diagnostic test for Typhoid and interventions to reduce the burden of infections acquired within hospitals.
Dr Nicola Burgess-Brown heads the Biotechnology Group at the SGC, which generates proteins suitable for structural and functional studies. Recombinant protein expression in host cells such as bacterial or insect cells facilitates the production of large amounts of proteins, which can be used for crystallisation to obtain the protein structure, or in cellular assays to look at their function. Collaborations with partners such as academics, industry and patient groups aim to find compounds that can be developed into potential drugs.
The development of new medicines is dependent on the identification of novel drug targets. CHEMICAL BIOLOGY
In the search for new medicines for cancer or inflammatory disorders, small molecules are invaluable tools for testing the activity of possible target proteins. Those small chemical compounds can also affect the morphology and phenotype of cell samples collected from patients, opening the possibility to develop new therapeutics.
Dr Direk Limmathurotsakul's research focuses on the epidemiology of melioidosis, a bacterial infection caused by Burkholderia pseudomallei. Melioidosis is endemic in at least 45 countries, but greatly under-reported. Up to 50% of cases seen in hospital die. Our researchers at MORU have produced a rapid diagnostic test that aims to improve both diagnosis and public awareness. Better coordination between researchers and policy makers is needed to face upcoming emerging infectious diseases.
Dr Claudia Turner heads the clinical research program at the Cambodia Oxford Medical Research Unit (COMRU), in collaboration with the Angkor Hospital for Children. Whereas children mortality has dramatically decreased over the past 15 years, almost half the remaining mortality still occurs during the first 4 weeks of age. Neonatology, or care of newborns, doesn't need to be difficult or expensive. Low cost intervertions involving communities, such as keeping babies warm, save lives.
Dr Chris Paton studies the use of open-source Electronic Health Records (EHR) software, online learning and mobile technology to improve healthcare delivery in low-resource settings. LEARNING HEALTH SYSTEM
In a learning health system, health care providers use electronic health records to identify problems, implement local solutions and check if the solutions are effective.
Health informatics, or the use of IT in healthcare, needs to find innovative solutions for low income settings, such as the use of open-source softwares and mobile technology. This approach has been used to deliver training to rural healthcare workers in Kenya.
With 390 million infections occuring each year, dengue is the most important mosquito-borne viral infection, and no vaccine is currently available. DENGUE
The majority of people infected with the dengue virus experience a flu-like febrile illness, but in a small proportion of patients, particularly children, the virus causes the blood vessels to become leaky which can induce shock and lead to death. Improved diagnosis and understanding of the disease process enable better outcomes for patients with severe dengue.
Growth hormones and cytokines regulate the key physiological processes of growth and differentiation as well as responses to injury and infection. FIBRODYSPLASIA OSSIFICANS PROGRESSIVA
Growth factors and signals are fundamental to many diseases. A single point mutation in the DNA coding for a bone morphogenetic protein is responsible for the development of FOP, a very debilitating disease where muscles are progressively turned into bones. Understanding these mechanisms allowed the selection of a drug, currently used to treat cancer, that may possibly be repurposed to treat FOP.
In pregnant women, severe malaria is responsible for high maternal mortality, and uncomplicated malaria results in in high morbidity. Professor Rose McGready works on the treatment and epidemiology of uncomplicated malaria in pregnancy. Pregnant women are particularly vulnerable as pregnancy reduces the immunity to malaria, increasing the susceptibility to malaria infection and the risk of illness, severe anaemia and death. For the unborn child, maternal malaria increases the risk of spontaneous abortion, stillbirth, premature delivery and low birth weight - a leading cause of child mortality.
Men who have sex with men (MSM) are a stigmatised group in Africa, but a predominant actor in the transmission of HIV. Professor Eduard Sanders is interested in putting together public health interventions to reduce HIV transmission in vulnerable populations, facilitating the early diagnosis of acute HIV infections and preventing its further spread. He also researches bacterial sexually transmitted infections in high risk populations, and HIV-1 early treatment trials.
Misfolded proteins can either create the loss of a cellular function, or escape degradation, causing aggregation diseases. Dr John Christianson's research focusses on ER-associated degradation, which is responsible for clearing non-functional and orphan translation products. These processes play a central role in inherited diseases such a cystic fibrosis and various forms of cancer. Dr Christianson's long term goal is to identify novel points of interventions for cancer therapies.
Chorea-Acanthocytosis: ChAc is a rare progressive neurological disorder caused by mutations in a very complex gene. Dr Antonio Velayos-Baeza is interested in two main projects: Chorea-acanthocytosis (ChAc), a rare autosomal-recessive disorder that is characterised by progressive neurodegeneration and red cell acanthocytosis (spiky red blood cells), and Developmental dyslexia, the most common of the childhood learning disorders.
Professor Robert Gilbert's research focuses on the molecular mechanisms underlying membrane pore formation and cell adhesion. Switching mechanisms within our cells are in part responsible for their development. MicroRNAs control a whole set of proteins associated with stem cell biology, particularly cancer stem cells. Targeting these components raises the potential for new anti-cancer therapeutics, which work by switching off protein production rather than inhibiting them later.
The main aim of Dr Xue's research is to understand the molecular and cellular mechanisms mediating inflammatory diseases, and to translate their findings into therapeutic concepts to treat these diseases. Drugs and treatments for inflammatory diseases are scarce and often induce major side effects. A better understanding of the molecular mechanisms governing inflammatory diseases would allow us to develop new drug and treatments, at great benefit for both patients and the NHS.
Resistance to drugs in bacteria can be aquired by swapping genes between individual bacteria. Computer programs developed by Dr Iqbal enable doctors to predict which antibiotics will be met with drug resistance, enabling the selection of the right drug. BIOINFORMATICS & PATHOGEN GENOMICS Dr Zamin Iqbal studies the DNA of bacteria and parasites, and compares the genomes of individual pathogens to track the spread of antibiotic resistance. Pathogens accumulate small genetic changes over time, and by tracking these changes, it is possible to map the spread of an infection. This enables better surveillance of pathogen evolution, within a host, within a hospital and across the world.
Computational and stastistical methods help us understand evolution as well as genetic disease. Professor Gerton Lunter is interested in investigating the processes of evolution and biology using computational methods. His focus is on sequencing data; Professor Lunter develops methods to investigate evolutionary questions in population genetics.
Melioidosis is a neglected tropical disease, and a major infectious killer in South East Asia. Melioidosis particularly affects people with diabetes. Dr Susanna Dunachie works on tropical diseases such as melioidosis, scrub typhus and vivax malaria. Melioidosis is a bacterial disease that results in pneumonia, liver and splenic abscesses and septic shock. The disease can reactivate after a latent period and is inherently resistant to many standard antibiotics. People continue to die around the world from this infection for which there is no vaccine. Understanding the disease is therefore crucial.
Over 250 Institutions participate in the effort of sharing data on the efficacy of antimalarial drugs, which involves standardising and re-analysing data. Professor Philippe Guérin is Director of the WorldWide Antimalarial Resistance Network (WWARN). The best lines of defence against malaria are avoidance of mosquito bites and effective drug therapy. WWARN tracks the emergence of antimalarial drug resistance to ensure that anyone affected by malaria receives effective and safe drug treatment.
Artemisinins are very poweful tools in the treatment of malaria, and the emerging loss of their activity has the potential to create a major public health problem. MALARIA TREATMENT
Dr Charlie Woodrow is based at MORU in Bangkok, Thailand, where he coordinates clinical and laboratory studies on resistance to artemisinins. Bringing together diverse datasets of clinical, in vitro and molecular data has helped better understand the emerging resistance, particularly in Myanmar.
Identifying and addressing ethical issues are key to the success of any clinical trials, particularly when working with vulnerable populations. Dr Phaik Yeong Cheah leads the Department of Bioethics & Engagement at the Mahidol Oxford Tropical Medicine Research Unit (MORU) in Thailand. She is particularly interested in ethical issues in community engagement, data sharing, consent and assent in paediatric research.
In settings with high level of poverty and over-stretched health services, researchers have even greater responsibilities to the communities and study participants. SOCIAL AND BEHAVIOURAL RESEARCH
A social scientist and public health researcher based in Kenya, Professor Vicki Marsh aims to understand and strenghten policies based on social and ethical aspects of international collaborations. Improving communications between researchers and the patients and local communities is not only ethically important; it can also lead to better research.
Melanoma or skin cancer is one of the fastest rising cancer types. When identified early, melanoma is relatively easy to cure, but once it starts to metastasise, it becomes very difficult to treat. DEREGULATION OF TRANSCRIPTION
The interface between signal transduction and transcription regulation coordinates gene expression. Deregulation of transcription is a key factor in cancer. Professor Colin Goding studies how a precise programme of transcription regulation is achieved, particularly in the transition between normal and cancer stem cells, and the parallels with normal stem cell populations.
Transcription is a tightly regulated process, where chemical modifications initiate the duplication of genetic material. This epigenetic process is often dysregulated in cancer, but it can be targeted with small molecule inhibitors. EPIGENETIC SIGNALLING
Professor Panagis Filippakopoulos is interested in the molecular mechanisms of transcription, where the formation of non-covalent protein complexes is mediated by post-translational modifications. Dysfunction in this epigenetic signalling process is linked to disease, particularly cancer.
Asthma and COPD (chronic obstructive pulmonary disease) are common conditions that affect the lives of many people. Dr Mona Bafadhel studies the pathophysiology of COPD (chronic obstructive pulmonary disease). There are broadly two inflammatory phenotypes of COPD that are clinically indistinguishable but have different treatment responses. Dr Bafadhel is working on the development of novel therapeutic strategies for COPD, particularly to treat the regular periods of worsened symptoms that patients experience.
Alteration of gene expression is fundamental to many diseases. A better understanding of how epigenetic proteins affect diseases provides a starting point for therapy development and the discovery of new drug. Professor Paul Brennan research focusses on epigenetics: the mechanisms that control gene expression. He studies how chemical probes interfere with epigenetic enyzmes that can be targeted to treat various diseases. Epigenetics combined with disease biology will ultimately accelerate drug discovery.
A missing step in a metabolic pathway leads to the build-up of toxic compounds, and the lack of materials essential for normal function. Professor Wyatt Yue explores how genetic defects lead to disease at the molecular level, by determining 3D structures and biochemical properties of enzymes and protein complexes linked to congenital genetic errors. Professor Yue works closely with clinicians and paediatricians to decipher the underlying genetic, biochemical and cellular mechanisms of these diseases. His long-term aim is to help design novel therapeutic approaches for metabolic diseases.
Economics and health are interlinked in many ways, as seen in the vicious cycle between poverty and ill health. Dr Yoel Lubell leads the economic team at the MORU Mathematical and Economic Modelling Group, based in Bangkok, Thailand. His research focuses on the evaluation of diagnostics, treatments and vaccines for infectious diseases, with the aim of providing guidance on malaria elimination and control of artemisinin resistance in the Mekong region.
Too high a dose can result in toxicity and side-effects, too low a dose can cause the illness to come back and at worse develop resistance. Professor Joel Tarning is Head of Clinical Pharmacology in our MORU Unit in Bangkok, Thailand. He's working towards drug dose-optimisation using novel pharmacometric modelling approaches. He is particularly interested in antimalarial treatments for children and pregnant women.
Dr Christiane Dolecek speaks about the research on enteric fever she conducted in Vietman and Nepal. Dr Christiane Dolecek's clinical research focuses on tropical diseases, in particular enteric fever and malaria. She has led enteric fever clinical trials in Vietnam and Nepal with the aim to systematically assess the current WHO recommendations as well as new treatment options.
Professor Peter Horby is Senior Clinical Research Fellow. His research focusses on epidemic diseases such as Ebola and bird flu, and crosses the disciplines of basic science, medical science and public health. Influenza, SARS & Ebola
Research on emerging infectious diseases can only be conducted during outbreaks. Although virology has improved, a well calibrated and effective public health response is often lacking. Epidemiological and clinical research as well as mathematical modelling will give us answers during the epidemics and help us provide better diagnostics and better treatments.
Dr Gareth Bond, Associate Member of the Ludwig Institute for Cancer Research, studies the influence of genetic variants on the origins, progression and treatment of human cancer. SNP - single nucleotide polymorphisms
There is great heterogeneity between individuals in their risk of developing cancer, disease progression and responses to therapy. Specific single nucleotide polymorphisms (SNPs) are associated with human cancers. They have the potential to help us identify individuals more at risk of developing cancer, and better target preventative or therapeutic strategies.
Dr Jenny Taylor is the Programme Director for the Genomic Medicine Theme, Wellcome Trust Centre for Human Genetics. Her research bridges the gap between genetics research and the use of its discoveries in diagnosis or treatment of medical conditions. Clinical diagnoses can be broad descriptions, but today's test results can help better understand the condition as well as target treatment. Cancer is a good example in which personalised medicine can help decide which molecular targeted therapy is most appropriate.
Identifying genes that increase the risk of bowel or other cancers allows us to offer preventative measures, such as removing tumours at an early stage. A better understanding of how and why cancers grow also helps develop improved treatments. Ian Tomlinson, Professor of Molecular and Population Genetics at the Wellcome Trust for Human Genetics, works on the identification of genes that predispose to colorectal and other cancers. His research focuses on the relative importance of selection and genomic instability.
Cancer research now generates huge amounts of data, and sophisticated computational tools are needed to answer biological questions. Making sense of this variability at molecular level will help us better tailor treatments to individual cancer patients. Dr Benjamin Schuster-Böckler heads the computational group at the Ludwig Institute for Cancer Research. His work has demonstrated that epigenetic modifications influence the mutational landscape in cancer cells. He studies the effects of DNA-binding proteins on transcription factors, with the aim to understand the regulation (and mis-regulation) of the transcription of important oncogenes and tumour suppressors.
Video microscopy aims to improve target discovery and drug development and to do so generates large volumes of data. Professor Jens Rittscher has a joint appointment between the Ludwig Institute for Cancer Research, the Target Discovery Institute and the Department of Engineering Science. His research aims to enhance our understanding of complex biological processes through the analysis of image data acquired at the microscopic scale.
Dr Sebastian Nijman develops new approaches to study signalling networks in cancer cells and uncover specific weaknesses, particularly in breast and lung cancer. This can be used to develop more effective drugs and to better guide treatment decisions. In the context of cancer, genetic diversity means that we respond differently to various treatments. Pharmacogenomics sits at the intersection between genetics and drugs. Better understanding of the genetic landscape of cancer and the recent increase of targeted drugs allow us to better match patients with the best treatments, improving care.
Microbiology in Thailand Acurately diagnosing infections is particularly challenging in tropical environments. Researchers at the Mahidol Oxford Tropical Medicine Research Unit (MORU) are working to develop effective and practical means of diagnosing and treating malaria and other neglected tropical diseases, such as dengue fever. The development of rapid tests for dengue, similar to pregnancy tests, allow rapid and acurate diagnostics in the field.
Infectious diseases in South East Asia The Mahidol Oxford Tropical Medicine Research Unit (MORU) is a collaboration between the University of Oxford and Mahidol University, and was established with the Wellcome Trust in 1979. MORU aims to fight the infectious tropical diseases affecting rural communities in Asia and elsewhere in the developing world.
MORU's malaria research aims to directly improve the treatment of the disease globally. It's researchers focus on the treatment of severe malaria, the spread of antimalarial drug resistance, and the pathophysiology of falciparum and vivax malaria. These studies are used to formulate novel adjuvant therapies, and have been translated into recommendations for the use of artemisinin based combination therapies.
Daniel Paris: Rickettsial Disease Rickettsial diseases such as scrub typhus are important causes of fever in southeast Asia especially in rural communities. Discovered quite recently and not big killers, these diseases are among the most under-reported and under-diagnosed illnesses that are both treatable and preventable.
Rickettsial studies at he Mahidol Oxford Tropical Medicine Research Unit (MORU) focus on the epidemiology and incidence of the disease using hospital-based fever studies in Thailand and Laos. Our research unit has developed highly improved acute diagnosis of rickettsial illness. MORU also has ongoing studies to determine the pathophysiological mechanisms of scrub typhus infection.
Oxford Health Systems Research Collaboration (OHSCAR) Professor Mike English leads the Health Services Unit at the KEMRI-Wellcome Trust Research Programme in Nairobi, Kenya. This unit aims to strengthen equality in access to affordable quality health care in Africa. Studies are based on health systems clustered around five main topics: malaria, service delivery & access, information for decision making, governance and financing.
Professor English leads efforts to develop multidisciplinary links with Oxford through the Oxford Health Systems Research Collaboration (OHSCAR).
Governance in practice Dr Sassy Molyneux's main interests reside in Social science and Ethics in Public Health. Over the years, social scientists have developed a programme of empirical work on research ethics. This work is based on an understanding that while the ethics of human subjects research may be universal, there can be big differences across contexts and circumstances in key ethical issues or principles.
Novel light microscopy techniques allow us to track single viruses. From a virus centric approach, we can now study interactions between the host and the virus. In the case of HIV, we could demonstrate that the virus might enter the cell through endocytosis. A better understanding of virus-cell interactions will ultimately help us test and develop new drugs and vaccines.
DNA replication and Cancer The process of DNA replication is complex, and mistakes can lead to genome instability. Surveillance systems are not always successful which results in mutations that have the potential to inactivate genes or change their activity. This can lead to cancer, and many chemotherapeutic drugs are designed to disrupt DNA replication. A better understanding of these mechanisms can help us develop new drugs with reduced side effects.
Over the past decade, data-driven science has produced enormous sets of data. The convergence of statistics and computer science, in the field known as machine learning, provide the means to understand these large datasets. Ultimately, machine learning algorithms will be develop into clinical decision making support systems.
Between research and humanitarian Professor François Nosten's work concentrates on infectious diseases at the Thai-Burma border. The main focus of his research is on malaria, especially malaria in pregnant women and emerging drug resistance of malaria parasites.
Tuberculous Meningitis Professor Guy Thwaites is trying to improve outcomes for patients with tuberculous meningitis, the most severe form of tuberculosis. 100, 000 people a year get tuberculous meningitis and without treatment 100% of people with the disease will die.
Innate immune system Professor Alison Simmons is interested in the molecular aspects of innate immune recognition, the primitive arm of the immune system that defends the host from infection by other organisms in a non-specific manner. Defects in the innate immune system can result in difficulty clearing infections but also in inflammation.
Structure of viruses Professor David Stuart studies the structure of viruses at the molecular level. His work is particularly interested in virus-receptor interaction and the basic puzzles of virus assembly and he uses structural biology to answer these questions.
Adult gastrointestinal stem cells The gastrointestinal tract is lined with a single sheet of epithelium that is replaced every 4-5 days. The base of a flask-shaped structured called the crypt is where the gastrointestinal stem cells are found. These divide to form daughter cells that travel up the crypt to replace these cells. Dr Simon Leedham's current research focuses on the cell-signaling pathways that control intestinal stem cells and the dysregulation of these pathways in cancer.
Inflammatory signalling Dr Mads Gyrd-Hansen aims to elucidate fundamental mechanisms governing pro-inflammatory signalling during innate immune responses, and through this, to better understand how aberrant inflammatory signalling contributes to tumour development and cancer progression.
Airway inflammation Ian Pavord is Professor of Respiratory Medicine and has been joint Chief Medical Advisor to Asthma UK since May 2008. He has developed new techniques to get a better idea about airway inflammation and uses this information to investigate the best treatments to prevent asthma attacks.
Genetics and genomics of Streptococcus pneumoniae Angela Brueggemann's main focus is using high-throughput genotyping and whole genome sequencing techniques and unique collections of isolates to understand pneumococcal evolution, especially evolutionary changes related to antimicrobial and vaccine selective pressures.
Professor Townsend tells us about lessons to be drawn from the history of immunology in Oxford, from 1979 onwards, until his current research on active and passive immunity to influenza. All these developments happened in Oxford because the atmosphere was right, open, researchers were encouraged to explore, and there was an enthusiasm in a great environment. Experiments and discoveries were made possible by the very open attitude of the supervisors at the time, telling their team that they they could do anything they wanted.
Professor Peter Donnelly tells us how genetics helps us to understand common diseases and develop new drugs. Understanding which variations in our DNA affect susceptibility to diseases can provide new insights into the disease process and lead to new treatments. Professor Peter Donnelly leads large collaborative human genetic studies, and his group develops and applies statistical methods to extract maximal information from the large datasets generated by genomic studies.
Dr Trudie Lang tells us how the Global Health Network facilitates collaboration and resource sharing. Clinical trials establish the evidence base for prevention and treatment of disease and are critically important in the field of Global Health. Dr Trudie Lang leads the Global Health Clinical Trials group, which aims to promote and improve the conduct of non-commercial clinical research across all diseases in resource-poor settings.
Professor Nick White talks about the future of artemisinin and other drug therapies for malaria. Malaria kills more than half a million people every year. Following a number of groundbreaking clinical trials, Professor Nick White and his Thailand team successfully demonstrated the effectiveness of artemisinin drug therapy for malaria in adults, children and infants. He also pioneered artemisinin combination therapy, the first-line treatment for malaria worldwide.
Professor Chris O'Callaghan tells us about the role of our immune system in vascular disease. The accumulation of fat in the arteries, such as cholesterol, can cause a thickening of the artery wall known as atherosclerosis. Professor Chris O'Callaghan is researching the role of the innate immune system in atherosclerosis to better understand immune responses to vascular disease. This may lead to improved treatments.
Dr Najib Rahman talks about his research on respiratory medicine. The Pleura are thin membranes that cover the surface of the lungs. Dr Najib Rahman specialises in areas of respiratory medicine including pleural disease and the conduct and analysis of respiratory trials. Dr Rahman is currently conducting clinical studies in malignant and infectious pleural disease, and is Clinical Director of the Oxford Respiratory Trials Unit.
Professor Jonathan Flint talks about his research on psychiatric genetics. It is now known that genetic variants can form the basis of psychiatric disorders, such as depression and anxiety. Professor Jonathan Flint is investigating the genetics behind psychiatric disorders, in particular the origins of stress-related conditions, such as anxiety and depression, for which we have relatively ineffective treatments.
Professor Stefan Knapp tells us how the development of chemical probes helps us to find new drugs. The role of proteins in cellular signalling and disease is best studied through the development of highly specific chemical inhibitors, which can serve as a tool molecule for functional studies. Professor Stefan Knapp works to determine the structure of protein molecules to understand their regulation and to aid the design of selective inhibitors that can be developed further into efficient drugs
Dr Sumi Biswas talks about the development of a vaccine aimed at the mosquito stage of the malaria parasite cycle. Malaria transmission-blocking vaccines aim to induce immunity against the parasites that infect mosquitoes. Such vaccines will prevent malaria transmission on a wider scale, focusing on the community rather than the individual. Dr Sumi Biswas is working on the development of transmission-blocking vaccines to prevent the spread of malaria.
Dr Liz Carpenter talks about her research on membrane proteins and drug development. Membrane proteins are the gateways to our cells - with nutrients, waste products, and even DNA and proteins entering and leaving cells via these tightly controlled proteins. Drugs often target membrane proteins; therefore, understanding their molecular structure helps us design better drugs. Dr Liz Carpenter uses X-ray crystallography to solve membrane protein structures. This information is then used to improve treatments for heart disease and neurological diseases.
Dr Alexander Finlayson tells us how MedicineAfrica aims to bring healthcare professionals around the world in a global expert network. Disparity in healthcare between the developed and developing world is a major global health problem. MedicineAfrica, an online health facility, aims to connect doctors and healthcare professionals in Africa to clinical support teams around the world. Dr Alexamder Finlayson established MedicineAfrica in 2008, and is now working to develop this platform for future users, such as medical students, doctors and nurses, in other countries including Palestine and India.
Professor Kay Grunewald tells us how structural cell biology can help us understand virus infection. Cells constitute the smallest autonomous units of life. The tightly regulated structural and functional organisation is currently only rudimentary understood. Professor Kay Grünewald uses electron cryotomography in combination with other techniques to analyse virus' 'life cycle' in situ, which requires an understanding of its transient structures at the molecular level. Imaging techniques allow us to understand the communication between the virus and the components of the cell it is infecting, which can ultimately help to treat infectious diseases.
Dr Christian Eggeling tells us how new imaging methods help us understand immunology at the molecular level. To study complex biological and immunological systems, such as living cells, scientists rely on highly sensitive and non-invasive analysis techniques. Super-resolution optical microscopy allows us to study immunological processes on the molecular level. We can get new insights into how our body reacts to viral or bacterial attacks. Dr Christian Eggeling's research focuses on the application and development of superior, ultra-sensitive, live-cell fluorescence microscopy techniques. This has the potential to help us design new drugs and developing new ways of treating diseases.
Professor David Jackson tells us about the role of the lymphatic system in immunity and cancer. The lymphatic system is a network of vessels collecting the fluids leaked from the blood vasculature. Its filtering function makes it an ideal compartment for the immune system. It is also a pipeline for metastasizing tumour cells to spread to distant tissues. Professor David Jackson studies how leukocytes and tumour cells enter the lymphatic vessels from the surrounding tissues. Professor Jackson's research has the potential to help us better control the spread of tumours, block unwanted immune responses in autoimmune diseases, block tissue rejection and make vaccines more effective.
Professor Graham Ogg talks about the role of our skin as a barrier against infection. Skin frequently represents the first point of contact with pathogens and allergens, but there is still very little known about the role of the surface immune system in fighting unwanted invaders. Barrier dysfunction can lead to the development of eczema. Understanding these mechanisms can help us develop new treatments targeting the skin, as well as the inflammatory response. Dr Graham Ogg aims to understand the role of skin immune responses by studying common skin diseases and infections.
Professor Fiona Powrie talks about the importance of our guts, and her research in gastroenterology.
Dr Simon Travis tells us how clinical trials bring tomorrows treatments to patients today. Before translating basic research into the clinic it is important first to undergo clinical trials in order to identify safe treatments and therapies for disease. Led by Dr Simon Travis the Gastroenterology Clinical Trials Facility at Oxford University works to translate basic research into clinical trials of novel therapies for gastrointestinal and liver diseases.
Professor Vincenzo Cerundolo tells us how research in immunology leads to the development of new cancer treatments. Immunotherapy stimulates the bodys immune system and can be a powerful treatment for cancer. With the aim of developing better treatment strategies for cancer patients, Professor Vincenzo Cerundolo is working to gain a better understanding of the cell-to-cell interplay required for optimal expansion and activation of tumour-specific T cell populations.
Professor Xin Lu talks about the links between cancer and regenerative medicine. Professor Xin Lu is the Director of the Oxford branch of the Ludwig Institute for Cancer Research. Her lab works toward identifying molecular mechanisms that suppress tumour growth and metastasis and focuses on understanding the factors that lead to uncontrollable cell growth.
Dr Jan Rehwinkel talks about the role of our innate immune system in our fight against flu virus. Dr Jan Rehwinkel and his group study the bodys immune reaction to viruses such as flu and HIV 1 which affect millions of people worldwide. The aim is to impact on the management of infectious diseases and the development of vaccinations. This work also has an impact on auto-immune diseases such as Lupus.
Dr John Frater talks about his research into finding a cure for HIV. It is increasingly apparent that highly active antiretroviral therapy (HAART) may not be the long-term solution to the management of HIV infection, and that other avenues need to be explored. As a result of various recent cases, the idea of eradicating HIV altogether is becoming less unimaginable to some scientists.
Professor Sarah Gilbert talks about her work on viral vectored vaccines. Professor Sarah Gilbert has been making and testing vaccines designed to induce T cell responses for ten years, chiefly using antigens from malaria and influenza. Based at the Jenner Institute, several of the vaccines developed in Professor Gilberts laboratory have progressed into Clinical Trials.
Professor Lars Fugger talks about his research on multiple sclerosis. Professor Lars Fugger focuses on translational studies in multiple sclerosis and uses a multidisciplinary approach. He is seeking to understand the molecular basis for the MHC association in MS and how MHC genes interact with environmental factors such as viruses. Professor Fuggers group consists of both basic scientists and clinicians.
Dr Raghib Ali talks about INDOX, the cancer research network in India. Dr Raghib Ali is the Director of INDOX Cancer Research Network. His main interest is in colorectal (bowel) cancer and other chronic, non-communicable diseases. Incidence of colorectal cancer in India has been relatively low historically; understanding why may help us establish risk factors and also lead to new treatments.
Dr Jay Berkley tells us about his work on childhood nutrition and immunity in East Africa. Dr Jay Berkley works in the KEMRI/Wellcome Trust Collaborative Research Programme in Kilifi, Kenya. His research interests include tackling infection and inflammation to prevent mortality in malnourished children. He is also an expert advisor on severe acute malnutrition to the Ministries of Health, and the World Health Organisation.
Dr Holm Uhlig talks about the role of the immune system in our gastrointestinal tract. Dr Holm Uhlig is based at the Translational Gastroenterology Unit and studies defects in the immune response and regulation leading to immunopathology. Dr Uhlig is interested in children with inflammatory bowel disease, and aims to understand the complex puzzle of molecular mechanisms involved.
Professor Richard Cornall tells us about his research on autoimmunity. Professor Richard Cornall aims to understand the causes of autoimmune diseases. Autoimmunity occurs when the immune system which is normally designed to attack pathogens ends up attacking the body. Professor Cornall is also interested in how people differ in their inherited susceptibility and why these differences are sustained in human populations by natural selection.
Dr Simon Draper tells us about his progress in malaria vaccine research. Dr Simon Draper's research interests include studies of vaccine induced malaria immunity. His group focuses on translational medicine. They will take their most promising vaccine candidates and manufacture them as clinical grade material. The next step is proof of concept clinical trials in healthy volunteers.
Dr George Warimwe talks about his research on Rift Valley Fever. Dr George Warimwe is working with the International Livestock Research Institute (ILRI) A Centre of Excellence in Africa, and the Jenner Institute to develop a vaccine against Rift Valley Fever in humans, that will also be useful as a vaccination against the disease in livestock.
Dr Katharine Owen talks about the different types of Diabetes in young adults. There are more forms of diabetes than the commonly known type 1 and type 2. Dr Katherine Owen investigates the different characteristics of monogenic diabetes with the aim of creating systematic diagnostics for aetiology of diabetes, and implementing that in clinical care. The ultimate aim is to promote personalized medicine for everybody with diabetes.
Dr Patrick Pollard tells us about his research on cancer metabolism. Cancer cells produce energy predominately by a high rate of glycolysis. It has been suggested that this change in metabolism is a fundamental cause of cancer. Dr Patrick Pollard aims to elucidate the alternative metabolic strategies used by cancer cells to proliferate, even under conditions of stress.
Professor Mark McCarthy tells us how genomics helps us understand diabetes. Professor Mark McCarthy (Robert Turner Professor of Diabetes) leads a multidisciplinary research team including clinicians, nurses and lab-based research staff. One of their major focuses lies in translating gene identification and genetic information into advances in functional understanding and clinical management.
Dr Richard Antrobus talks about his research in the development of a universal flu vaccine. Dr Antrobus has been conducting a Phase I study of a Universal Vaccine for Influenza. Progress so far indicates that this approach induces a potent T cell response, and Dr Antrobus is currently assessing whether this response is equally potent in the elderly - one of the 'at risk' groups of the Influenza virus.
Dr Arturo Reyes-Sandoval tells us about his research on a vaccine against Plasmodium vivax. Dr Reyes Sandoval aims to develop a novel malaria vaccine against Plasmodium vivax, one of the four malaria parasites that affect humans. P. vivax is found in Africa, Asia, Latin America and the Western Pacific. 40 percent of the world's population is exposed to the disease that is responsible for around 130 to 350 million clinical cases every year.
Colin Baigent, Professor of Epidemiology, Clinical Trial Service Unit, Oxford, talks about why the drug Statin saves lives.
Dr Helen Fletcher talks about progress in the development of a vaccine against tuberculosis. Dr Helen Fletcher works on multi-partner projects to discover biomarkers of protection from TB disease, develop clinical trials capacity in Africa, and develop new vaccines for TB. Dr Fletcher has also developed her own research programme on transcriptional profiling of immune responses following both TB and malaria vaccination.
Dr Opher Gileadi tells us how cells maintain genome integrity and how we can use it in our fight against cancer. Dr Opher Gileadi studies the structure and chemical biology of proteins involved in DNA repair and in recovery from DNA damage. DNA damage can be both a cause of cancer and a tool in fighting cancer, and the work aims to uncover ways to better target and destroy cancer cells.
Dr Kerstin Luhn talks about her research on Dengue infection. Dr Luhn is investigating the effect of Dengue virus infection on innate immune cells to understand why Dengue, unlike other viral infections, is associated with high levels of immunopathology. An in vitro Dengue model is used and results are confirmed with Dengue patient samples from a cohort in Vietnam.
Professor Tomas Hanke tells us about his research on HIV vaccine development. The long term aim for Professor Tomáš Hanke is to develop a safe, effective and accessible HIV-1 vaccine. His group tests novel ideas and vaccine strategies, and focusses on a safe but rapid translation of the most promising laboratory results to phase I/II clinical trials in human volunteers.
Professor Stephen Gough talks about the development of personalised diabetes treatment. Prof. Stephen Gough believes that you cannot give every patient affected by diabetes the same treatment; where people react differently to treatments provides a background to his research. Prof. Gough aims to provide the right treatment to the right person at the right time in their disease for optimum results.
Professor Gil McVean tells us how statistical genetics helps us understand and treat disease. Prof Gil McVean is the Head of Bioinformatics and Statistical Genetics at the Wellcome Trust Centre for Human Genetics. His research covers several areas in the analysis of genetic variation, combining the development of methods for analysing high throughput sequencing data, theoretical work and empirical analysis.
Dr Leanne Hodson talks about her research on liver fat metabolism. Dr Leanne Hodson's research focuses on fatty liver disease, defined as having over 5 percent liver fat, and a 'silent disease' as many people are not diagnosed. Dr Hodson aims to find targets for new medications which will help lower the risk of accumulating liver fat.
Dr Barbara Fielding talks about her research on the metabolism of fatty acids. Dr Barbara Fielding believes that nutritional advice should be based on a thorough understanding of metabolic responses to food ingestion, and that it is important to investigate the metabolism of dietary fat after both single and multiple meals, as is customary daily behaviour in Western societies. Ultimately, this will help to make specific dietary recommendations.
The largest trial investigating the benefits of cholesterol lowering in kidney patients. The Study of Heart and Renal Protection (SHARP) concluded that around a quarter of all heart attacks, strokes, and operations to open blocked arteries could be avoided in people with chronic kidney disease by using the combination of ezetimibe and simvastatin to lower blood cholesterol levels.
Dr Ellie Barnes talks about her research on Hepatitis C and her work on a T cell vaccine. Dr Ellie Barnes aims to develop a prophylactic and a therapeutic hepatitis C virus vaccine to combat a global epidemic currently infecting 170 million people worldwide. Many chronically infected patients silently develop complications of liver disease that can include hepatocellular cancer, liver cirrhosis and liver failure.
Dr Anna Gloyn talks about her research on the genetics of Diabetes. The research undertaken by Dr Anna Gloyn focuses on using naturally genetic variants identified in humans as tools to identify critical regulatory pathways for insulin secretion and action. Current research projects are focused on the translation of genetic association signals for type 2 diabetes and glycaemic traits into molecular mechanisms for diabetes and clinically useful tools.
Dr Tao Dong tells us about her collaborations in China on infections such as HIV, flu and Hepatitis B. Dr Tao Dong's research interests include antigen-specific T cell responses in human virus infections and their contribution to the consequences of the disease. Hepatitis B virus has recently been added to the list of viruses which Tao and her group studies, which includes influenza and hepatitis C virus/HIV co-infection.
Prof. Arjen Dondorp tells us about his work on severe malaria and the development of new therapies. Prof Arjen Dondorp is the Deputy Director and Head of Malaria Research at the Mahidol-Oxford Tropical Medicine Research Unit in Bangkok, Thailand. His main research interests include the pathophysiology and treatment of severe malaria, antimalarial drug resistance and the improvement of intensive care practice in developing countries.
Professor Sarah Rowland-Jones tells us about her work on HIV with children in Africa. Prof. Sarah Rowland-Jones' work mainly focuses on anti-viral immunity, and in particular how immune responses modify the outcome of HIV infection. Her research aims to contribute to the design of vaccines and immunotherapies against HIV infection, including HIV-2 infection, in developing countries where an effective vaccine is desperately needed.
Professor Patrik Rorsman talks about Diabetes and how beta cells within the pancreas control insulin secretion. Patrik Rorsman is professor of diabetic medicine in the Oxford Centre for Diabetes, Endocrinology and Metabolism. Professor Rorsman has been at the forefront of research on hormone-secreting cells in the pancreas for more than 20 years, work that is highly relevant to understanding the causes and treatment of type 2 diabetes. The Wellcome Trust award will allow him to study further the metabolic and hormonal regulation of hormone secretion in the pancreas.
Dr Lucy Dorrell tells us how our immune system controls HIV and how we can live with this virus. The aim of Dr Lucy Dorrells' research is to develop immunotherapy to reduce the dependence of those infected with HIV-1 on their current treatment - antiretroviral therapy (ART). This is because 9 million of the estimated 33 million people living with HIV/AIDS today are not able to access the ARTs which they are in immediate need of.
Professor Paul Klenerman talks about our relationship with persistent viruses, such as Hepatitis C. Prof. Paul Klenerman studies the evolutionary relationships between persistent viruses and their human hosts. He aims to understand the role of our immune responses in determining the outcome of Hepatitis C virus infection. Hepatitis C virus infects around 200 million people worldwide and is a major cause of liver disease.
Professor Dominic Kwiatkowski talks about his work on global health, how genomics can help us fight infections such as malaria. Prof. Dominic Kwiatkowski aims to reduce the burden of infectious disease in the developing world. He translates advances in genome science into clinical and epidemiological applications. He mostly works on malaria but many of his tools and methodologies in genetics, statistics, informatics and ethics have applications for other diseases.
Dr Dianne Newbury talks about the contribution of genetics to specific language impairment. Dr Dianne Newbury is looking for the genes that predispose to Specific Language Impairment, a complex genetic disorder. Two regions, located on chromosomes 16 and 19, are linked with this disorder. Interactions between several normal genetic variants and environmental factors make certain individuals more vulnerable to language problems.
Dr Seph Borrow tells us how her research on HIV Immunology helps design better vaccines. There is an urgent need for vaccines to combat persistent infections like HIV. Dr Seph Borrow is studying factors affecting virus control by HIV-specific CD8+ T cells, to inform the design of T cell-based HIV vaccines. She is also exploring the possibility of harnessing innate immune responses to combat HIV.
Professor Chris Pugh tells us about the links between genetics, renal disease and oxygen sensing. The kidney plays a central role in our metabolism, by controlling various physiological balances. Genetics plays an important role in renal disease since gene defects lead to all sorts of malfunctions. Prof. Chris Pugh is working on the oxygen sensing functions of the body; whilst these were discovered in the context of erythropoietin production the underlying system controls about 1000 genes.
Dr Silvia Paracchini talks about the influence of Genetics in Dyslexia. Dr Silvia Paracchini aims to indentify the genetic components of dyslexia and understand the underlying biology. Other disorders such as Specific Language Impairment or Attention Deficit Hyperactivity Disorder are commonly linked to dyslexia. Dr Paracchini is looking for possible common genes for these clinically distinct disorders. Her research has the potential to uncover some of the biological mechanisms involved in human cognition.
Professor Sir Andrew McMichael tells us about recent developments in the search for a vaccine against HIV. Prof. Sir Andrew McMichael is working on human immunology and vaccines, first looking at flu virus and now HIV. His current lines of research include analysing early molecular events in HIV infection, T cell immune response to HIV and the use of vaccination to control HIV infection.
Dr Bee Wee tells us about Palliative Care in Oxford and her research on end of life care and fatigue. Dr Bee Wee is the Head of Palliative Care Research and Development, based at Sir Michael Sobell House in Oxford. Her current lines of research include End of life care for people with incurable cancer and advanced non-malignant disease, Symptom management and Rehabilitation.
Professor Kevin Marsh tells us about his research on Tropical Medicine in Kenya. Prof. Kevin Marsh has a broad research interest in child health in the tropics, with a particular focus in the immune epidemiology of malaria. Prof. Marsh is director of the KEMRI Wellcome Programme in Kenya; he also coordinates the malaria immunology group within the programme.
Professor Yvonne Jones talks about cell-cell communication and how this can help us develop new drugs. Prof. Yvonne Jones is director of the Cancer Research UK Receptor Structure Research Group. Her research focuses on the structural biology of cell surface recognition and signalling complexes. Receptors embedded in the surface are potential targets for therapeutic intervention in many diseases including cancer.
Professor Fredrik Karpe explores the links between obesity and diabetes. Prof. Fredrik Karpe initiated the Oxford Biobank for prospective genetic epidemiological research. Integrative physiological and genomic approaches are used to study lipid and carbohydrate metabolism. Prof. Karpe also studies the links between obesity, insulin resistance, type 2 diabetes and cardiovascular disease.
Dr Benedikt Kessler tells us how proteomics helps find biomarkers. In most living organisms, the ubiquitin-proteasome system is responsible for the degradation of proteins, either because they're damaged or they reach the end of their life span. Ubiquitin marks a protein for elimination. Alterations in this process are responsible for many human diseases. Dr Benedikt Kessler studies the role of deubiquitylating enzymes that remove ubiquitin from substrate proteins.
Professor Tim Key tells us about the role of life style and diet in the development of cancer. Prof. Tim Key is interested in the role of diet and hormones in the development of cancer, particularly cancers of the breast, prostate and bowel. Prof. Key is the principal investigator of the EPIC-Oxford cohort of sixty thousand participants, for various studies on cancer, hormones and nutrition.
Dr Katja Simon tells us about her research on autophagy in red blood cells. Autophagy is the cellular process in which cells degrade their toxic waste and damaged organelles. Dr Katja Simon studies how the lack of autophagy seems to trigger DNA mutations and the development of leukemic cells. This might help us make better use of current therapies and develop new ones.
Dr Paul Bowness tells us about his work on spondyloarthritis. Dr Paul Bownessis works on Ankylosing Spondylitis, the commonest form of spondyloarthritis. This rheumatic disease seems to be caused by an overacting immune system. It has a major genetic component: at least 5-10 genes are known to contribute the disease, with HLA-B27 being by far the most important. Dr Bowness studies how these genes work in the immune systems of both healthy people and patients with arthritis.
Dr Cecilia Lindgren explores the links between obesity and genetics. Obesity and its consequences are major and growing challenges for health care worldwide. Over 30 genes associated with body mass index have now been identified. Dr Cecilia Lindgren uses genetic and genomic approaches to better understand the underlying mechanisms and pathways involved in the regulation of overall energy balance.
Dr Hal Drakesmith tells us how his work on iron availability can help us fight infections. Iron plays essential biochemical roles in oxygen binding, ATP synthesis and DNA metabolism. The level of iron available in different tissues is controlled by the small peptide hormone hepcidin. Dr Hal Drakesmith studies how hepcidin is modulated during infections, since iron availability plays an important role in the course of major infectious diseases such as HIV, malaria and Hepatitis C. Genetic variation plays an important role in individual susceptibility to many common diseases. New insights into genetic variants which modulate gene expression allow us to better understand why people develop these diseases. We can then target treatments much more effectively. Ultimately, we will be able to identify patients at risk of developing disease.
Dr Helen McShane has been working on a new TB vaccine for 10 years. She explains why developing countries are especially in need of a new vaccine since HIV and TB epidemics overlap and show a devastating synergy. There are about 9 million new cases and 1.7 million deaths every year from tuberculosis. Dr Helen McShane developed MVA85A, a vaccine with the aim to boost the cellular immune response induced by BCG. BCG, now over 100 years old, remains the only licensed vaccine against Tuberculosis. It confers good protection against severe disease and meningitis but doesn't protect against lung disease. MVA85A was the first vaccine of the new generation to enter into efficacy testing. It is currently being tested in The Gambia, Senegal and South Africa.
Professor Chas Bountra explains how new drugs can offer novel treatments for neurodegenerative and gastrointestinal diseases, as well as pain disorders. Professor Chas Bountra is interested in identifying and validating target proteins for drug discovery. Various technologies and strategies have allowed him to progress promising clinical candidates into Phase I, II, III studies, and to market. Drug candidates are first selected by screening compounds capable of binding to a target protein. Those compounds are then tested in various assay systems, healthy volunteers and finally in patients. Academic research excels at defining good target proteins. Pharmaceutical companies then facilitate the transition from basic research to clinical trials, producing new therapies for patients.
Dr Julian Knight explains how new insights into genetic variants which modulate gene expression allow us to better understand why people develop these diseases, and allow us to target treatments more effectively. Dr Julian Knight studies how genetic variation between individuals affect the way immune and inflammatory genes are expressed. This helps understand genetic susceptibility to common conditions such as infectious, inflammatory or autoimmune diseases. He recently published a book titled 'Human Genetic Diversity, functional consequences for health and disease'. Genetic variation plays an important role in individual susceptibility to many common diseases.
Dr Erika Mancini explains how malfunctions in the regulation of chromatin structure often leads to complex multi-system diseases and cancer, notably leukemia. Dr Erika Mancini is interested in the role of chromatin in the regulation of gene transcription. All our cells contain the same set of genes, but only some of them are transcribed at any point in a particular tissue. Regulation of gene transcription is strongly linked to chromatin, physical packaging of the DNA within the nucleus. Molecular Mechanisms influencing DNA packaging Chromatin plays an important role in the regulation of gene expression. The movement of nucleosomes, packing and unpacking DNA, is governed by chromatin remodelling ATPases. Malfunctions in the regulation of chromatin structure often leads to complex multi-system diseases and cancer, notably leukemia.
Dr Climent Casals-Pascual explains how the development of new tools to diagnose and manage malaria more effectively will allow us to decrease the mortality of this condition. Dr Climent Casals-Pascual is interested in severe malaria, particularly its diagnosis and clinical management. Clinical symptoms of severe malaria are similar to those of other diseases like pneumonia and meningitis. In tropical countries, poor diagnosis often results in sub-optimal treatments. Integrating proteomic, genomic and clinical data will help us explain differences in clinical outcome in severe malaria.
Professor Adrian Hill has been studying the immune system and malaria susceptibility in African children for years. We asked him about his latest findings in the development of vaccines against malaria. Professor Hill develops vaccines against malaria based on inducing cellular immune responses (T lymphocytes) instead of the more commonly used stimulation of antibodies. Prophylactic vaccines developed in Oxford are now showing great promise in clinical trials.
Dr Krina Zondervan is interested is women's health conditions, particularly endometriosis. Dr Zondervan studies genetic, molecular and environmental factors influencing this complex disorder. Women suffering from endometriosis experience severe pelvic pain and may suffer from infertility. Endometrial-like cells develop outside the uterine cavity. These cells are influenced by hormonal changes and respond similarly as the cells lining the uterus. Causes of endometriosis remain unknown and treatments are limited to either surgery or the use of hormonal drugs.