Tools to investigate parasite biology Flashcards
How can we work out what the parasite causing infection is?
- Can take cross sections of the parasite and reconstruct via 3D imaging
- Can look at the morphology and structure using microscopy, does the parasite look similar to known parasites?
- Can perform whole genome sequencing and compare to known databases, is there any homology etc?
How can we test to see if a parasite is infectious in humans?
- Can test in humans, tends to be unethical
- Can use experimental models
When were humans purposely infected with Plasmodium?
When infected with neurosyphilis in the pre-antibiotic era
What is neurosyphilis caused by?
Bacterial infection in the brain
How can neurosyphilis be treated by malaria?
Malaria causes relapse fever
Causes bouts of fever which can kill the bacteria
Treating disease with fever is known as?
Pyrotherapy
Which Plasmodium species was used to infect individuals?
Plasmodium vivax
The Plasmodium vivax could be treated with?
Quinine which was available
After the discovery of antibiotics such as penicillin?
Malariotherapy fell into disuse
What are some experimental models to test if a parasite is infectious?
- Human tissue culture
- Organ-on-a-chip
- Animal models e.g. humanised mice
Liver-on-a-chip was developed by?
University of Oxford
MIT
What was tested on liver-on-a-chip in 2018?
HBV infection
Organ-on-a-chip advantages?
- Can mimic infection
- Can study lifecycles and cell invasion
- Can test drugs
- Can create personalised medicines
University of Pennsylvania liver-on-a-chip?
Bioengineered the chip which includes fluorescent markers that can detect key cell functions e.g. cell death/damage
Benefits of mouse models?
- Laboratory mice are genetically identical
- Short life-cycle
- Can be easily stored
- Produce high numbers of offspring
- Can be humanised - mimic human immune system
- Easy to look after
- Can alter their microbiome
- Can perform knockouts/deletions
- Can overexpress genes
- Can test drugs in mice
Which herbicide was discovered for treatment of malaria?
Artemisinin
Artemisinin was discovered by?
Chinese scientist Tu YouYou
Derived from which plant?
Sweet wormwood
Has been used by Chinese herbalists for?
~2000 years
As a response to resistance developing?
Monotherapy is discouraged
What therapy does WHO recommend?
Artemisinin based Combination Therapy: ACT
This therapy is focussed on using other drugs with artemisinin to reduce the chance that resistance develops
What has been found to be the cause of artemisinin resistance?
K13 mutations
Mutations in the propeller region of kelch 13 gene
Where is the kelch gene located?
Chromosome 13
How can we identify what causes resistance?
Genomics
Compare resistant strains to non-resistant strains
Look for SNPs
Look to see if there are any changes to proteins as a result of the SNPs
Genetically engineer parasites, see if the SNP is actually linked to resistance- in order to confirm