FightMalaria@Home

FightMalaria@Home

Crowdsourcing antimalarial drug discovery

Goal:

To discover novel targets for antimalarial drugs.

Context:

Malaria kills a child every 45 seconds. The disease is most prevalent in poorer countries, where it infects 216 million people and kills 650,000 each year, mostly African children under 5 years old [WHO]. And Plasmodium falciparum continues to evolve resistance to available medication. We therefore urgently need to discover new drugs to replace existing drugs. Importantly, these new drugs need to target NEW proteins in the parasite. The FightMalaria@Home project is aimed at finding these new targets.

Resources:

The Plasmodium falciparum genome has been sequenced, the proteome has been mapped, and protein expression has been confirmed at various stages in this apicoplexan's life cycle. Numerous crystal structures of target proteins are also available, and the remainder have been modelled using available structural templates. Excitingly, large research organisations (GSK, Novartis) have already tested millions of compounds and found nearly 19,000 hits that show promising activity against Plasmodium falciparum [MMV]. But they don't know which target protein is inhibited by these compounds. Drug discovery and development will be significantly enhanced by knowing the target protein for each of these hits.

Problem:

We plan to dock each of the 18,924 hits into structures of each of the 5,363 proteins in the malaria parasite. The computational power needed is enormous.

Solution:

We aim to harness the donated computational power of the world's personal computers. Most computers only use a fraction of their available CPU power for day-to-day computation. We have built a BOINC server that distributes the docking jobs to donated 'client' computers, which then do the work in the background. By connecting 1000s of computers this way, we'll be able harness the equivalent power of large supercomputers. If you would like to get involved, please follow the very quick installation instructions here.

Validation:

Once the computation for the FightMalaria@Home project is complete, we'll need to validate the targets in a laboratory. Sadly, this will cost a significant amount of money. We hope that academic groups around the world will take the data that we will generate and test the targets in their own laboratories. But to ensure success, we would like to do some of this testing ourselves. For that we need money. Lots of it. Money for salaries for at least one scientist, money for consumables (protein purification reagents, assay reagents), money for laboratory space, money for overheads, etc., etc...
Any donated funds that are not used for the validation of novel targets in malaria, or for replacement hardware to keep the BOINC server going, will be donated to the non-profit organisation Medicines for Malaria Venture.
Donations:

We have created a separate PayPal account for the FightMalaria@Home project. Donated money will go to this account, and not to a personal account. 


WHAT WE NEED:

1: New Server(s).

With 16,000 PCs connected in 127 countries, our old and donated server is running beyond its capacity. We urgently need new hardware to ensure that the work units are efficiently distributed and processed. When the FightMalaria@Home project ends, we will use the same system and hardware for a similar 'FightTB@Home' project which will be aimed at finding novel targets and drugs against Tuberculosis.


2: Protein Expression and Validation Assays.

The main aim of the FightMalaria@Home project is to predict the protein targets for compounds that kill malaria. For these results to be believed by the scientific and pharmaceutical community, they need to be validated in the laboratory. To do that, we'll need to produce these proteins in sufficient quantities to be able to use them in binding studies which will hopefully confirm that the specific protein is the target for the selected compound. This is labour intensive work that costs about €5,000 per protein.



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    • €25 
    • 53 mos
  • Claudio Bottaccini 
    • €50 
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  • Anne Ebertus 
    • €10 
    • 76 mos
  • Jay Eichelberger 
    • €50 
    • 77 mos
  • Anonymous 
    • €10 
    • 94 mos
See all

Organizer

Anthony Chubb 
Organizer
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