Translational Medicine

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.