Malaria

Question 1

What targets can be targeted in liver stage?

Answer 1

UIS4 (upregulated in sporozoite) is required in early liver stage development after the PVM is formed
UIS4-GAP = no liver proliferation

fabb/f is required in later stage development
fabb/f-GAP = no blood stage infection as no merozoites are released from the liver schizont

Question 2

What processes can be targeted in the blood cycle?

Answer 2

N-myristoylation
NMT inhibitors kill parasites in vitro

Ubiquitylation
E1 (ubiquitin activating enzyme) inhibition my UBA1 blocks parasite growth and schizont development

Question 3

What targets are there in gametogenesis? (anti-transmission targets)

Answer 3

p45 and p48 is required for gamete adhesion/fertilisation

HAP2 is required for gamete fusion

PF16 - armadillo protein is a bad target as its homologue SPAG-6 is also required for sperm motility

Question 4

What targets are there in the mosquito asexual stages?

Answer 4

PPKL and SHLP1 (phosphatases) are required for ookinete motility and midgut invasion

ESP1 is required for sporozoite egress from oocyst

TRAP, MAEBLE and CSP are required for salivary gland invasion. CSP is the target of gsk’s Mosquirix vaccine.

Question 5

Which genes maintain asexual schizogony?

Answer 5

HP1 and Hda2

Question 6

Which gene does high levels of LysoPC repress

Answer 6

GDV1