Two MRC The Gambia scientists, Dr Climent Casals-Pascual (Malaria Programme) and Dr Thushan de Silva (Viral Diseases Programme) are the latest recipients of competitive MRC research awards.
Dr Casals, who has won a Clinical Scientist Fellowship, will be conducting a four year study into severe malaria (SM) caused by the parasite Plasmodium falciparum, an important cause of death mainly in children under five years of age. The current definition of SM includes various severe syndromes with associated mortalities ranging from 4% to 35% despite adequate treatment.

Proteins are involved in almost any biological function. The comprehensive study of all the proteins (the proteome) provides a global perspective of how a biological system works. Therefore, emerging technologies like proteomics offer powerful new tools to disentangle the mechanisms of complex diseases and help identify new therapeutic targets.

The plasma proteome includes all the proteins that can be found in the fluid phase of the blood. The study aims to identify the plasma proteome of children with SM, which will help in the identification of key molecules that participate in the development of severe disease. The identification of these molecules or biomarkers will provide a better understanding of the underlying mechanisms of SM, which may be translated into better diagnosis, management and eventually decrease the mortality of severe malaria.

The title of Dr Casal’s research project is ‘Pathobiological classification of severe malaria based on an integrated approach of high-throughput proteomics and systems biology’. He will be based at Oxford University, and will spend two months a year in The Gambia.

HIV antibody response: keys to vaccine development
Dr Thushan de Silva, the recipient of a three year Clinical Research Training Fellowship, will be conducting a project called ‘Neutralizing antibody responses in HIV-2: role in disease progression and protection from subsequent HIV-1 coinfection’

Natural infection with many viruses results in the production of antibodies which help clear the virus and protect us from subsequent re-infection. Eliciting such an antibody response is the basis of many effective vaccines, but unfortunately little is understood about protective antibody responses in HIV, which has hindered HIV vaccine design. Despite sharing many similarities with HIV-1, most patients with HIV-2 do not develop AIDS (although a minority do) and the reasons for this are not entirely clear. This project proposes to compare neutralizing antibody responses in HIV-1 and HIV-2 infected patients and explore whether stronger responses are found in HIV-2 infected patients who do not progress to AIDS, when compared to HIV-2 progressors and HIV-1 patients; at a stage where the immune system is relatively well preserved.

Early studies also suggested that HIV-2 antibodies could render HIV-1 non-functional and although some previous studies claimed HIV-2 infected individuals may be protected against subsequent HIV-1 infection, the majority suggest no protection or even an increased risk of acquiring HIV-1 superinfection. The research therefore proposes to compare HIV-1 cross-neutralizing antibody responses and enhancing antibody responses in HIV-2 patients who go on to acquire HIV-1 superinfection, with those who have remained HIV-2 mono-infected despite possible exposure to HIV-1.

Such information could provide vital clues to how the HIV surface interacts with antibodies and the importance of eliciting an antibody response in future HIV vaccines.

Dr de Silva’s study will commence in September 2008. MRC Scientists Donate Books to Medical School