Translational Medicine

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.