Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - MALARIA TARGETS ID (Mapping the Targets of Antimalarial Compounds Through Chemical Profiling.)

Malaria is the most devastating parasitic infectious disease affecting over two hundred million people every year and killing close to half a million children. The WHO estimates that half of the word population is at risk, with 1.2 billion people having a high risk of infection, mainly in developing countries. Unfortunately, growing resistance to front-line drugs including the current gold standard for malaria therapy, i.e. artemisinin-based combination therapy, has made the identification of novel antimalarial targets and the development of new therapies extremely urgent.
In an effort to synergize basic research with malarial drug development the pharmaceutical industry has identified thousands of new compounds with antimalarial activity. These hits represent a treasure-throve of chemical tools to study parasite biology and identify new targets. However, in order to harness the potential benefits of these compounds it is crucial to understand how these small molecules kill the malaria parasite.
Our group has been using chemical biology approaches to identify the targets of some of these bioactive compounds with the goal of validating new antimalarial targets. In particular, we use small molecule tools called activity-based probes (ABPs) that allow us to simultaneously monitor the activity of dozens of enzymes in the malaria parasites. These tools can be used in screening methods to determine whether small molecules are able to inhibit any of the enzymes that can be monitored using ABPs. Over the last two years we have been focused on identifying targets among two enzyme families known to play essential roles in parasite development. After optimizing the assay conditions, which now allow us to screen around 400 compounds/day against 40 different enzymes, we have identified five compounds that modify the activity of some of these enzymes. We are currently using chemical proteomic approaches to identify these targets, which we aim to genetically validate as novel antimalarial targets over the next two years.
Dr Deu obtained a PhD in comparative biochemistry from UC Berkeley and pursued a Postdoc in chemical biology at Stanford University. He returned to Europe in 2013 after receiving a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society to start his independent research career at the National Institute for Medical Research (currently the Francis Crick Institute) in London. His research group is one of first to combine state-of-the-art chemical biology and genetic approaches to identify and validate novel antimalarial targets, to study their biological function, and eventually to start new antimalarial drug development programs in collaboration with industry. Since receiving the CIG in 2014, Dr Deu has increased the size of his group from two to six members including four postdocs and two PhD students, one of which is funded through the CIG grant. Dr Deu has established a strong research program including collaboration with academic group in the UK, Europe (Poland, Netherlands, Czeck Republic, Italy and Spain), United States and Australia, as well as joined research projects with industry (GlasgoSmithKline).

Reported by

United Kingdom


Life Sciences
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top