Using model organisms to facilitate advances in medical parasitology Flashcards
LO
- The learning outcomes for this part of the module are related to pharmacological strategies for parasite control.
- After studying this topic, the lecture and recommended reading you should be able to:
- Understand the core processes for drug discovery in medical parasitology
- Critically evaluate the use of model genetic organisms for the study of parasitic helminths.
What are some of the challenges that need to be addressed with medical parasitology?
Population-based chemotherapy programmes
Complex life cycles; intimate association with human host
Emerged and emerging anthelmintic resistance
Low-cost therapies
i.e., the need the safe, broad spectrum, resistance-breaking, low-cost novel nematicidal drugs
Target site for currently used anthelmintics
With the experimental routes to new drugs like Phenotypic-based screening, what can this be tested on and what effect is seen?
Name some good model organisms
C. elegans
Ascaris suum
These are both nematode round worms
Why are model organisms used when testing out new drugs?
- Easy (and cheap) to culture and maintain in the lab
- Phylogenetically related
- Conserved neurobiology
- (very) genetically tractable
- Suitable for high-throughput chemical screening
- Suitable for delineating mode of action
Tell me how they are easy (and cheap) to culture and maintain in the lab
How are nematodes phylogenetically related?
What may be used to evaluate drug targets in parasitic species in the future?
‘model hopping’
What needs to be done for ‘model hopping’?
identify gene of interest in parasitic nematode
identify orthologous gene in C. elegans
obtain phenotype of C. elegans mutant e.g. drug resistance
generate transgenic C. elegans expressing the parasitic gene and test whether this reinstates sensitivity to the drug
Suitable for high-throughout chemical screening
How are model organisms suitable for delineating mode of action?
Ivermectin receptor
Benzimidazole mode of action
Levamisole receptor
Emodepside receptor*
*Guest et al. 2007 on BB, extra reading
… and mechanisms of resistance…
What are the two main mechanisms for delineating the mode of action?
Mutations in drug targets
Detoxification
What are the limitations to the model organism approach?
nAChR genes present in C.elegans and parasitic nematodes
What is in site for the future?
