Research Projects

Giardia lamblia, a pathogenic protist, is the most common cause of protozoal diarrhea worldwide. Treatment-refractory giardiasis is particularly prevalent in India, where high endemicity of the parasite is a major cause of reinfection. A therapeutic agent targeting the actively-feeding trophozoite form of the parasite within the host and blocking its transition to the cyst stage will be an effective deterrent against community transmission. Membrane fusion machinery, including NSF and α-SNAP, is crucial for trophozoites' uptake of nutrients and their transition to cysts, enabling the parasite's transmission to new hosts. This proposal aims to characterize these factors and determine the feasibility of targeting them for therapeutic purposes. Giardia expresses two closely-related NSF paralogues and three paralogues of α-SNAP, which are considerably diverged from each other. Preliminary data indicates that some of these paralogues discharge certain parasite-specific roles. Targeted inhibition of the precise paralogue, engaged in parasite-specific function, is likely to cause less side effects. Experiments will be conducted to determine if the paralogues of NSF and/or α-SNAPs discharge non-canonical roles in Giardia, such as maintenance of its complex cytoskeletal structures.