Grant: Operating Grant

Leishmania is a parasite of humans that causes a disease called leishmaniasis that can be fatal if not treated. There are three forms of leishmaniasis: cutaneous, mucocutaneous and visceral, that are elicited by various species of Leishmania. This disease is found in 98 countries with the estimated number of cases currently at 500,000 for visceral and 1.5 million for cutaneous leishmaniasis. There is no vaccine and the drugs used to treat leishmaniasis are very toxic to humans. As with many other parasites, Leishmania has a two stage life cycle involving an insect vector, the sandfly, and humans. Leishmania is transferred to humans when an infected sandfly takes a blood meal. Leishmania then infect and multiply inside white blood cells. Research is proposed to identify the genes and molecules in both Leishmania and human white blood cells that are involved in promoting the infection, growth and persistence of Leishmania. These studies are aimed to identify new drug targets and new drug therapies for the treatment of leishmaniasis. Current treatments for leishmaniasis are becoming increasingly ineffective due to the emergence of drug-resistant strains. Therefore, there is an urgent need to develop new classes of drugs that are active against Leishmania. Antimicrobial peptides are naturally occurring peptides used in organisms ranging from bacteria to mammals as part of a defense mechanism. Some of these have been shown to have anti-leishmanial activity. Our research will study the effectiveness of these peptides to treat different forms of leishmaniasis. This will involve re-designing the peptides for use in humans. Due to the similarities between Leishmania and other intracellular pathogens, understanding the mechanisms involved in causing leishmaniasis and the development of new therapies, will also help in the treatment and prevention of similar diseases.