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cAMP signalling in Trypanosoma brucei - basic cell biology and drug target identification

English title cAMP signalling in Trypanosoma brucei - basic cell biology and drug target identification
Applicant Seebeck Thomas
Number 109245
Funding scheme Project funding
Research institution Institut für Zellbiologie Departement Biologie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Cellular Biology, Cytology
Start/End 01.05.2006 - 31.08.2010
Approved amount 347'300.00
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All Disciplines (2)

Discipline
Cellular Biology, Cytology
Medical Microbiology

Keywords (11)

parasitic protozoa; malaria; sleeping sickness; Chagas disease; leishmaniases; phosphodiesterase inhibitor; drug development; cyclic nucleotide signalling; african sleeping sickness; inhibitor; chemotherapy

Lay Summary (English)

Lead
Lay summary
Lead:Protozoal diseases represent major public health problems in large parts of the world. A better understanding of signal transduction mechanisms in these parasites may pave the way for developing better, safer and more effective medication.Background:Chemotherapy against major protozoal diseases such as Malaria, Chagas disease, the leishmaniases and African sleeping sickness is at a dismal state. Drug development has not progressed very much over the last century, while drug resistance is rapidly increasing. Our project explores the cyclic nucleotide specific phosphodiesterases (PDEs) of Trypanosoma brucei, the causative agent of African sleeping sickness, as a new class of drug targets. PDEs are important in cellular signal transduction. Their inhibition is expected to disrupt vital signalling pathways and thus to block parasite proliferation. This laboratory has demonstrated that PDEs are highly conserved between parasitic protozoa and their human (or animal) hosts. The human PDEs are well studied drug targets, and inhibitors such as Viagra® have caught the public interest far beyond the medical profession. The fact that parasite and human PDEs are so closely related allows to exploit the vast expertise of the pharmaceutical industry for developing parasite-specific PDE inhibitors. Goal:The goal of the project is to demonstrate that PDEs are interesting targets for developing novel anti-parasitic compounds, and to demonstrate the feasibility of this general approach. The fact that human PDEs are extensively investigated by the pharmaceutical industry, combined with the observation that humane and parasite PDEs are very similar, offers the unique opportunity that the available expertise can be applied without modification for finding and developing such compounds. This concept has raised the active interest of several major companies, a coordinated effort between industry and academia in several countries is now in operation, and several other companies are considering such programs for the near future.Significance:Drug development efforts has traditionally been targeted to parasite-specific, “exotic” enzymes, and the results have not been impressive. Our project opens a new perspective in turning the current paradigm on its head and trying to use the highly conserved PDEs as targets. This approach is likely to facilitate the drug development pipeline since industry already commands a vast expertise in developing highly specific inhibitors against the human PDEs. Applying this expertise to the very similar parasite PDEs may be a relatively simple task and highly time- and cost-effective.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
67225 cAMP signalling in Trypanosoma brucei - basic cell biology and drug target identification 01.01.2003 Project funding

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