Tools to investigate parasite biology

Question 1

How can we work out what the parasite causing infection is?

Answer 1

• 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?

Question 2

How can we test to see if a parasite is infectious in humans?

Answer 2

• Can test in humans, tends to be unethical

- Can use experimental models

Question 3

When were humans purposely infected with Plasmodium?

Answer 3

When infected with neurosyphilis in the pre-antibiotic era

Question 4

What is neurosyphilis caused by?

Answer 4

Bacterial infection in the brain

Question 5

How can neurosyphilis be treated by malaria?

Answer 5

Malaria causes relapse fever

Causes bouts of fever which can kill the bacteria

Question 6

Treating disease with fever is known as?

Answer 6

Pyrotherapy

Question 7

Which Plasmodium species was used to infect individuals?

Answer 7

Plasmodium vivax

Question 8

The Plasmodium vivax could be treated with?

Answer 8

Quinine which was available

Question 9

After the discovery of antibiotics such as penicillin?

Answer 9

Malariotherapy fell into disuse

Question 10

What are some experimental models to test if a parasite is infectious?

Answer 10

• Human tissue culture
• Organ-on-a-chip
• Animal models e.g. humanised mice

Question 11

Liver-on-a-chip was developed by?

Answer 11

University of Oxford

MIT

Question 12

What was tested on liver-on-a-chip in 2018?

Answer 12

HBV infection

Question 13

Organ-on-a-chip advantages?

Answer 13

• Can mimic infection
• Can study lifecycles and cell invasion
• Can test drugs
• Can create personalised medicines

Question 14

University of Pennsylvania liver-on-a-chip?

Answer 14

Bioengineered the chip which includes fluorescent markers that can detect key cell functions e.g. cell death/damage

Question 15

Benefits of mouse models?

Answer 15

• 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

Question 16

Which herbicide was discovered for treatment of malaria?

Answer 16

Artemisinin

Question 17

Artemisinin was discovered by?

Answer 17

Chinese scientist Tu YouYou

Question 18

Derived from which plant?

Answer 18

Sweet wormwood

Question 19

Has been used by Chinese herbalists for?

Answer 19

~2000 years

Question 20

As a response to resistance developing?

Answer 20

Monotherapy is discouraged

Question 21

What therapy does WHO recommend?

Answer 21

Artemisinin based Combination Therapy: ACT

This therapy is focussed on using other drugs with artemisinin to reduce the chance that resistance develops

Question 22

What has been found to be the cause of artemisinin resistance?

Answer 22

K13 mutations

Mutations in the propeller region of kelch 13 gene

Question 23

Where is the kelch gene located?

Answer 23

Chromosome 13

Question 24

How can we identify what causes resistance?

Answer 24

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