Epigenetic regulation of antigenic variation in the malaria parasite

1. - Malaria- The Journey to find a Cure Epigenetic regulation of antigenic variation in the malaria parasite Dr Chris Tonkin Chris Tonkin

2. Malaria is a major human disease ➜ 2 billion people at risk; 300 to 500 million clinical cases 1 to 3 million deaths per year; mainly young children = 1 death every 30 seconds ➜ Symptoms: • Anemia • Tachycardia (fast heart rate) • fever, chills, nausea • flu-like symptoms • severe cases - coma and death

3. Global Impact of Malaria • Affects people in tropical and subtropical regions, where 85-90% of deaths occur in Africa

4. Economic Impact of Malaria Poverty Malaria

5. Economic Impact of Malaria Poverty Malaria

6. Economic Impact of Malaria Poverty Malaria

7. Economic Impact of Malaria Poverty Malaria • Countries affected by malaria have five times smaller economies

8. Economic Impact of Malaria Poverty Malaria • Countries affected by malaria have five times smaller economies • The burden of malaria has been estimated to cost $12 billion/ year • Cost of health care • Days lost in education • Working days lost due to sickness • Decreased productivity due to brain damage from cerebral malaria • Loss of investment and tourism

9. History of Malaria • Medieval translation : bad (mal) air (aria) • Formally known as Ague or Marsh Fever (association with swamps) French Army Doctor Charles Louis Alphonse Laveran Working in the military hospital of Constantine in Algeria

10. Discovery of the malaria parasite

11. Discovery of the malaria parasite Diseased

12. Discovery of the malaria parasite Diseased Normal

13. Discovery of the malaria parasite Diseased Normal

14. The malaria parasite is carried by Mosquitos Sir Ronald Ross working in the Presidency General Hospital in Calcutta who proved in 1898 that malaria is transmitted by mosquitoes. Anopheles spp. Only pregnant female mosquito’s feed on blood

15. Mosquito Human The malaria parasite is carried by Mosquitos Sir Ronald Ross working in the Presidency General Hospital in Calcutta who finally proved in 1898 that malaria is transmitted by mosquitoes. Anopheles spp. Only pregnant female mosquito’s feed on blood

17. Treatment for malaria is limited DDT. Initially Hailed as a miracle, thought that it would wipe out malaria. Resistance is widespread Insecticides: Only a handful. Parasite resistance to drugs is very common. Drugs: No effective vaccine. The holy grail of malaria research. Vaccine:

18. New treatments for malaria are Urgently needed

19. How do we find you treatments if we don’t know how the parasite works? Rational therapeutic design

20. ↓ ↓ Find the smallest biological components that cause disease Design new therapeutic strategies The reductionist approach Complex disease (Malaria)

21. Reducing complexity -Genes- ↓ ↓ Proteins /Enzymes(Factory workers) Design drugs and vaccines Genes are the blueprint for all life Genes (Managment team)

22. With Understanding of the Biology We Can Design New Treatments

23. With Understanding of the Biology We Can Design New Treatments

24. With Understanding of the Biology We Can Design New Treatments Enzyme

25. With Understanding of the Biology We Can Design New Treatments Enzyme

26. With Understanding of the Biology We Can Design New Treatments Enzyme

27. Two good targets for therapeutic intervention

32. Finding genes that are essential for parasite virulence NEEDLE IN A HAYSTACK! Years/Lifetime

33. parasite gene GFP A needle in a Haystack

35. A needle in a Haystack parasite gene

36. A needle in a Haystack ✂ ✂ parasite gene

37. A needle in a Haystack ne pa Gene knockout

38. ne pa Genetically modified malaria parasites Invade?

40. Research takes a very long time This work took 3 people working fulltime for 6 years Not all research works and gives good results Now we have 8 new anti-malarial targets that we did not have before

41. Is this all worth it? Research is expensive and slow Malaria is the biggest killer in the world We don’t have any choice