The genetics of metabolic diseases

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.