|dc.description.abstract||Poly is a novel, essential protein in Drosophila melanogaster, loss of function
of which results in late larval lethality. Importantly, Poly is evolutionarily conserved
with a human homologue. poly mutation was isolated in a P-element mutagenesis
screen that aimed to generate a larger collection of single P-element induced
mutants. Mutant poly larvae are characterized by extreme larval longevity without
pupation, formation of melanotic masses, smaller imaginal discs and brains, and
abnormal nuclear morphology in neuroblasts. During the course of my project, I
attempted to identify cellular processes and pathways that Poly might be involved in.
Interestingly, my data suggest that Poly is a novel interactor and regulator of Insulin
receptor/target of rapamycin (InR/TOR) signalling in Drosophila.
Linking environmental cues to cell growth and metabolism is an essential
process that multicellular organisms need to accomplish successfully for normal
development. InR/TOR signalling is a highly conserved pathway that mediates the
link between the environment and cellular processes such as growth, metabolism and
ageing. My analysis in Drosophila suggests that Poly interacts physically with the
InR and mutation of Poly leads to an overall down-regulation of InR/TOR signalling
in Drosophila as revealed by decreases in the phosphorylation levels of Akt, S6K
and 4E-BP - all downstream effectors of this pathway. In addition, loss of poly
results in constitutive activation of autophagy in Drosophila fat body and a decrease
in stored triglyceride levels. Furthermore, I show that localisation and levels of Poly
protein are dependent on insulin action in both Drosophila and human cells.
Together, these data suggest that Poly is a novel mediator of InR signalling that
promotes an increase in cell growth and metabolism.
Taking into consideration the observed poly mutant phenotype, I also
investigated the potential involvement of Poly during cell cycle progression and the
Drosophila innate immune response. While my analysis suggests that poly loss of
function does not have a direct effect on cell cycle progression, alteration of Poly has
consequences on various aspects of the Drosophila innate immune response.
Therefore, I conclude that the Drosophila innate immune response is a cellular
process in which Poly plays a crucial role.||en