dc.contributor.advisor |
Hall, Christopher |
|
dc.contributor.advisor |
Warman, Guy |
|
dc.contributor.author |
Rolland, Leah |
|
dc.date.accessioned |
2021-11-04T23:03:52Z |
|
dc.date.available |
2021-11-04T23:03:52Z |
|
dc.date.issued |
2021 |
en |
dc.identifier.uri |
https://hdl.handle.net/2292/57267 |
|
dc.description |
Full Text is available to authenticated members of The University of Auckland only. |
|
dc.description.abstract |
Circadian rhythms are in place to optimise the timing of fundamental physiological processes to synchronise them with daily environmental changes. The host immune response to bacterial infection has a circadian rhythm. This rhythm has two characteristic states, an active state where there is
enhanced clearance of bacterial infections and an inactive state with less effective bacterial clearance.
These two states coincide with the organism’s behaviour: active immunity when the organism is
active, and the threat of infection is most significant, and scaled-down immunity when the organism
is inactive or resting. Clock proteins control circadian rhythms in cellular function. The molecular
clock operates within almost all cell types in the body, including the phagocytic cells of the innate
immune system (neutrophils and macrophages), and influences their ability to respond to infection.
Therefore, the molecular clock within these immune cells is a unique target to modulate immune
responses for therapeutic benefit. However, whether other critical bactericidal components of the
innate immune system (such as the complement system) are under the control of the molecular clock
is very poorly understood. Recent work from the Hall laboratory has shown that zebrafish larvae
deficient of the light-responsive clock gene per2 show decreased expression of complement factor
c3a.3. To validate and expand on these initial findings, we confirmed that per2 and c3a.3 expression
in the larval zebrafish liver and that under steady-state, per2 but not c3a.3 shows time-of-day
differences in expression levels across the 14h:10h LD cycle. Under infection, the magnitude of c3a.3
expression corresponds with endogenous levels of per2 expression. Over-expression of per2 in the
liver of per2-/- larvae rescues reduced c3a.3 expression in the liver of per2-/- larvae, and confirms the
requirement for Per2 in the expression of c3a.3 at steady-state. This work furthers our understanding
of how the innate immune system can adapt to anticipate infections and provides novel mechanistic
insights into the molecular clock’s regulation of the anti-bacterial complement system. |
|
dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
Masters Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
|
dc.rights |
Restricted Item. Full Text is available to authenticated members of The University of Auckland only. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
|
dc.title |
All Systems Go: Timing of the Host Response to Infection |
|
dc.type |
Thesis |
en |
thesis.degree.discipline |
Biomedical Science |
|
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Masters |
en |
dc.date.updated |
2021-09-30T21:53:56Z |
|
dc.rights.holder |
Copyright: the author |
en |