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    Mechanistic target of rapamycin (mTOR) activation during ruminant mammary development and function : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Palmerston North, New Zealand
    (Massey University, 2013) Sciascia, Miriama
    This thesis examines the abundance of total and activated mechanistic target of rapamycin (mTOR) pathway components in the developing and functional ruminant mammary gland. mTOR pathway activation is stimulated by a wide range of intra- and extracellular signals, such as amino acids (AA) and hormones, making the mTOR pathway a potential candidate for the development of intervention strategies designed to increase ruminant lactation potential. Tissues from two trials shown to improve lactation potential; dam-fetal nutrition and exogenous growth hormone (GH) administration during lactation, were used to measure changes in total and activated mTOR pathway protein abundance. Results show mammary glands of d 140 fetal lambs carried by maintenance fed dams and dairy cows administered exogenous GH, had increased abundance of total and activated mTOR and mitogen activated protein kinase (MAPK) pathway proteins. Increased abundance was associated with changes in biochemical indices. In the GH study MAPK pathway activation was stimulated by IGF-1 signaling whilst mTOR pathway activation was proposed to be mediated by AA signalling. Data from the GH study shows, L-arginine a known activator of the mTOR pathway, was the only AA reduced in both plasma and the lactating gland. Upstream factors were not identified for the phenotype observed in the dam-fetal nutrition study, but similar mechanisms were proposed. To elucidate the potential regulation of mTOR pathway activation by L-arginine and examine the effect on milk production, in vitro bovine cell culture models were evaluated. Results show that none of the models evaluated produced a lactating phenotype – a pre-requisite to accurately study the lactating gland in vitro. Finally, this thesis shows L-arginine administration from d 100 to d 140 of pregnancy, in twin bearing ewes had no effect on mTOR protein abundance or activation. However, administration from d 100 to parturition improved maternal gland health. In summary, this thesis associates improved lactation potential with increased total and activated mTOR pathway protein abundance, and the administration of L-arginine during late gestation with improved gland health. These findings provide fundamental knowledge that may lead to the development of novel technologies to increase ruminant gland performance and health.
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    A molecular genetic analysis of the requirement of TOR kinase signalling for plant growth : a thesis presented in partial fulfilment of the requirements for the degree Doctor of Philosophy in Plant Biology at Massey University, Palmerston North, New Zealand
    (Massey University, 2015) Rexin, Daniel
    Eukaryotes have developed a highly complex mechanism to incorporate signals from nutrient, energy, stress, developmental, and environmental cues to modulate their growth. To promote this growth, eukaryotes have to coordinate the expansion in cellular mass and size through macromolecular synthesis with the increase in cell number through division. This demands a complex orchestration of a plethora of cellular processes such as transcription, protein synthesis, metabolism and cell wall synthesis. The TARGET OF RAPAMYCIN (TOR) pathway was identified as a central integrator of this growth-regulating mechanism. Components of this pathway, including the TOR kinase and its interaction partners REGULATORY-ASSOCIATED PROTEIN OF TOR (RAPTOR) and LETHAL WITH SEC 13 PROTEIN 8 (LST8), are highly conserved among eukaryotes. This includes plants, for which the adaptation to changing environmental conditions is particularly important given their sessile lifestyle and highly plastic development. This work sought to further expand the knowledge of how TOR function was adapted to suit the requirements of plants. Therefore, I analysed genetic knock-out mutants of raptor in Arabidopsis thaliana, which resulted in a severe reduction of growth but did not cause an early developmental arrest as reported by previous studies. Detailed analysis of these mutants further revealed defects in the development of trichomes, gametophytes, and the polar extension of root hairs and pollen tubes. Potential causes for these defects were indicated by lower DNA content and limited ROS accumulation in raptor mutants. High similarities between raptor and lst8 mutants indicated that the formation of TOR complexes as found in other eukaryotes might not be functionally conserved in plants. Further, I adapted a CRE/lox system for the induction of mosaic deletions of RAPTOR, which indicated no tissue-specific requirement for RAPTOR functions within the root of A. thaliana, but demonstrated a role in the regulation of meristem size. To conclude, this data presents further evidence for an altered requirement of RAPTOR and LST8 function for TOR signalling in plants compared to fungi and animals. This thesis revealed novel functions of TOR in plant development, ROS homeostasis and endoreduplication. It further draws attention to the connection with other signalling pathways to regulate growth and development in plants.