Zoology - Theses
Permanent URI for this collection
Search Results
1 - 10 of 105
-
ItemThe ecological role of canopy-forming fucoid algae on temperate intertidal rocky shores(University of Melbourne, 2012)Understanding the role species play in ecosystems is vital to understanding how ecosystems function. Increasing anthropogenic and natural disturbance to coasts including the influence of climate change has highlighted the need to understand the function of species, especially those that cover large geographic ranges and dominate available space. Canopy-forming algae and seagrasses have been shown to provide habitat for associated species in subtidal environments through the provision of substrate for colonisation by algae and invertebrates; and the environmental conditions they modify through their structure, such as available light, and water flow. Studies on canopy-forming algae on rocky intertidal shores in Europe, Northern America and New Zealand have found evidence for an ecosystem engineering role, though until now this has been untested on Australian shores. Examination of species associations with the canopy-forming alga Hormosira banksii along Victorian rocky shores found differences in species assemblage occur in comparison to areas of shore where canopy is absent, adding to the overall reef biodiversity. Subsequent experimental investigation tested the ecological function of H. banksii and found that canopy-cover alters the species� ability to modify environmental conditions including temperature and light intensity, and as a consequence the species that can associate with the alga. The ecological role of the northern hemisphere fucoid alga Ascophyllum nodosum was also experimentally investigated to test the consequence of a loss of canopy biomass. Destruction of the A. nodosum canopy that reduces its cover over the underlying substratum was found to reduce the ability of the canopy to modify environmental conditions and as a consequence the species assemblage that are associated with intact A. nodosum canopy. Partial thinning of no more than 50% of the fronds arising from the holdfasts didn�t alter species assemblages or the physical conditions measured in comparison to controls indicating resilience to this level of disturbance. The function of intact canopy-forming algae was correlated with measures of substratum rugosity and the presence of abiotic microhabitats on the shores studied. The abundances of some macroinvertebrates were found to vary in relation to indices of substratum complexity, although this was idiosyncratic through time. Macroinvertebrates occupied a range of microhabitats available on the shore. Species strongly associated with the canopy were most often found to occupy canopy-dependant microhabitats such as holdfasts and fronds. But neither of these factors altered the function of the canopy algae as an ecosystem engineer. The results of this thesis allow prediction of the consequences of damage to intertidal canopy algae (ecosystem engineers). Both Hormosira banksii and Ascophyllum nodosum may be monitored and managed as a surrogate for shore biodiversity.
-
ItemFish responses to seagrass habitat fragmentation(University of Melbourne, 2009)Marine organisms that inhabit coastal waters increasingly have to deal with habitat fragmentation and concomitant increases in edge habitat. Effective conservation of coastal habitats requires an understanding of how and why organisms respond to these habitat changes. Seagrass is a critical marine habitat that is becoming increasingly fragmented. To understand how fish living in seagrass respond to fragmentation, I actively fragmented artificial seagrass habitats (single, continuous 9 m2 patches fragmented to 4 discrete 1 m2 patches) and evaluated changes in fish abundance. Total fish abundance was unaffected by fragmentation, and this was consistent through time (1 day, 1 week, 1 month). If fish crowded into remnant seagrass fragments, then crowding effects may explain the lack of decline in fish abundance that would otherwise be expected from seagrass habitat loss. Progressive removal of seagrass (16 m2 patches to 4 m2) showed that fish temporarily (?1 day) crowd into remnant patches, but crowding effects could not explain the longer-term persistence of fish in fragmented seagrass. I then tested the hypothesis that fish are more abundant at seagrass edges than interiors (i.e. �positive edge effects�) and that the effects of seagrass habitat loss on fish abundance were offset by an increase (25%) in edge habitat in fragmented patches. I found that fish were 3 times more abundant at edges than interiors in continuous seagrass (single, 9 m2 patches), but in patchy seagrass (4 discrete 1 m2 patches) there was no difference, which is probably because pipefish perceived patchy seagrass as consisted entirely of �edge� habitat. To test whether the observed edge effects in continuous seagrass were caused by increased availability of food at edges, I estimated the abundance of food across continuous seagrass patches. Food abundance peaked at seagrass edges and was 16% higher than samples taken from patch interiors. To separate causality from correlation, I supplemented interiors of continuous seagrass with food and found that edge effects ceased, which indicated that fish were moving from patch edges to interiors in response to food supplementation. This provided evidence that fish were more abundant at seagrass edges due to greater food availability.
-
ItemAltitudinal distribution of two invasive leafminers, Liriomyza huidobrensis (Blanchard) and L. sativae Blanchard (Diptera: Agromyzidae) in Indonesia(University of Melbourne, 2008)My thesis assessed the altitudinal distribution of two invasive leafminers., L. huidobrensis and L. sativae (Diptera: Agromyzidae), and examined the extent of environmental factors influencing their distribution. It has been well known based on studies conducted in laboratory that both species have different response to particularly temperature and host, but no study has been conducted to assess impacts of both factors and others in influencing altitudinal colonization patterns. A comprehensive survey was undertaken in the mountainous area of Dieng, the province of Central Java, Indonesia by collecting infested leaves, trapping adults, mapping habitat composition and recording the temperature. This study revealed that the distribution of both species differed with altitudes. Liriomyza sativae were only found and dominated at low altitudes, where L. huidobrensis were found across the entire gradient and dominated at high altitudes. Hosts did not limit the distribution of both species, but it may have had indirect effects on the dominance of L. huidobrensis. At high altitudes where the host faba beans preferred by this species were common, L. huidobrensis dominated, whereas at low altitude where less preferred hosts such as cucumber and long bean were common, L. huidobrensis was less common than L. sativae. The survey and the field experiment indicate that temperature may have limited the distribution of L. sativae because this species was absent where temperatures occasionally fell below 10�C. However, temperature did not limit the distribution of L. huidobrensis. This is consistent with a population growth model using only temperature as an explanatory factor. A comprehensive survey also indicated that there was no evidence of parasitoids limiting leafminer distributions. Parasitoids were found at all altitudes where leafminers were present Twelve parasitoids were identified which fell into three families Asecodes delucchii (Boucek), A. erxias (Walker), Chrysocharis sp., Cirrospilus ambiguus Hansson & LaSalle, Closterocerus sp., Hemiptarsenus varicornis (Girault), Neochrysocharis beasleyi Fisher & La Salle, N. formosa (Westwood), N. okazakii (Kamijo), and Quadrastichus liriomyzae Hansson & LaSalle are from the Eulophidae family, Gronotoma micromorpha (Perkins) is from the Eucolidae family, and Opius chromatomyiae Belokobylskij & Wharton is from the Braconidae family. Diversity of parasitoid declined with altitude and was negatively associated with percentage of parasitism, which increased with altitude. My study also investigated changes of morphological characters along the altitudinal gradient. Morphology only changes with altitude in L. huidobrensis, and this appeared to be driven both by genetic and environmental factors. The morphological changes may reflect adaptation to climatic conditions across the altitudinal gradient. Competitive interactions were considered in the laboratory and in the field. My study revealed that competition only occurred in laboratory where intraspecific competition was stronger than interspecific competition, although the latter was also detected. Intraspecific competition gave an advantage for rare species whereas in interspecific interactions there was no advantage to any one species. In the field experiments, there was no evidence of competition between both species because densities of leafminers were low. In field surveys the densities of leafminers were also usually low, suggesting that in field populations competition might be uncommon and have little impact on the altitudinal distribution of the species.
-
ItemThe role of the peptide hormone relaxin in cardiac fibrosis(University of Melbourne, 2007)Relaxin is a peptide hormone primarily synthesised in the corpus luteum during pregnancy, with a range of actions related to functional modifications of the reproductive tissues and parturition. Relaxin is transported via the circulation to its target tissues, where it is thought to stimulate physiological effects through the activation of a high-affinity G protein-coupled receptor (LGR7). In the heart, these effects may include modulation of the quantity and composition of the extracellular matrix (ECM), the network of macromolecules that provides structural and functional support to the myocardium. A number of factors play an important role in the regulation of the ECM, including ECM components themselves (such as fibrillar collagen) and ECM-degrading enzymes known as matrix metalloproteinases (MMPs). This thesis examined the role of relaxin in the regulation of these factors using a novel animal model, the relaxin-deficient (Rlx-l-) mouse. Previous work has shown that aged male Rlx-l- mice develop ventricular fibrosis (ECM accumulation) as a result of increased collagen expression, a phenotype that increases in severity with advancing age (Du, Samuel et al. 2003). These and other findings led to the suggestion that relaxin has anti-fibrotic properties in vivo. The Rlx-l- mouse model was used to further examine the role of this peptide in the regulation of the cardiac ECM. Initial studies in 2 - 8 month-old male mice demonstrated that relaxin deficiency does not cause increased collagen mRNA synthesis or excessive collagen deposition in the ventricular myocardium. Furthermore, there was no influence of relaxin on the expression of MMPs. In the cervix of pregnant mice (a well-known target tissue for the hormone), however, relaxin deficiency resulted in marked upregulation of several MMPs. The effect of relaxin treatment in vivo was then tested by chronic administration of the hormone to male Rlx-l- mice. Seven month-old mice, but not twelve month-old mice, responded to treatment with an upregulation in the synthesis of not only MMP (in accordance with the classic anti-fibrotic actions of the hormone) but also collagen genes in the ventricles, suggestive of a positive feedback mechanism activated by ECM degradation. This study demonstrated for the first time that relaxin concurrently stimulates both MMP and collagen gene expression in the heart, indicating that the anti-fibrotic effects of this hormone may not be as clear-cut as previously thought. In this thesis it was also demonstrated that LGR7 but not relaxin is expressed in the mouse heart. These data may explain why exogenous relaxin was able to induce effects in the heart, because there are LGR7 receptors present. In contrast, as there is no relaxin ligand expression in the heart, this may explain why relaxin deficiency did not influence gene expression or collagen deposition. Interestingly, two other novel relaxin-like ligand/receptors pairs were also identified as being expressed in cardiac tissues: relaxin-3/GPCR135 and Insl5/GPCR142. The functions of these ligands/receptors await further study. In summary, this thesis has contributed to the understanding of the role and potential mechanisms of action of both endogenous and exogenous relaxin in the mouse heart, and has clarified the relevant components of the paracrine cardiac relaxin system.
-
ItemNo Preview AvailableThe ecology and song of the duetting Eastern whipbird (Phosphodes olivaceus)(University of Melbourne, 2005)In this thesis I investigate the function of antiphonal duets, using as my model system the Australian eastern whipbird, Psophodes olivaceus. Fieldwork was carried out between 2000- 2003 on a colour-banded population of eastern whipbirds at Mimosa Rocks National Park, near Tathra, NSW. Eastern whipbirds form stable, long-term, socially monogamous pair bonds with a low rate of pair divorce. Males and females show sex role convergence in parental care and territory defence. While only females build the nest and incubate, both sexes feed offspring at the nest, with males feeding nestlings at a higher rate than females. On fledgling the brood of two is divided and each parent cares exclusively for one fledging during an extended period of post-fledging care. Males and females together defend an exclusive territory throughout the year. Competition for territories at this site is intense, due to a high rate of adult survival, limited dispersal by offspring and an extremely low rate of territory turnaround, despite the presence of numerous unpaired adult 'floaters'. Intra-sexual competition between females appears to be particularly strong given that sex ratios from nestling through to unpaired adult stages are female-biased. Eastern whipbird males and females coordinate their songs to form precise duets that are initiated exclusively by the male. Males and females each possess a repertoire of different song types, which are combined non-randomly to form specific duet types. Females produce two types of song: response songs, which are mainly used in the context of a duet, and 'type n' songs which are used only as solo songs. Both sexes share most of their songs with same-sex neighbours and the repertoire of song types appears to play an important role in allowing song type-matching during territorial interactions with intruders. Playback experiments suggest that the sexes differ in the extent to which they are influenced by the song types of rivals and partners during interactions. Males matched most of their songs with the song type broadcast by the speaker during simulated intrusion by male rivals. Females, in contrast, always fitted the song types of their partners rather than matching the songs of female rivals. By replying to their partner, females may be signalling their commitment to the pair bond, or demonstrating their own, or their partners, paired status to female rivals. Further playback experiments confirmed that females showed a more aggressive response to simulated intrusion by female rivals than male rivals, and answered a higher proportion of their partner's songs to form duets in the presence of a same-sex rival. Female eastern whipbirds therefore appear to reply to their partners in order to defend their exclusive position within the partnership. This behaviour appears to be the consequence of high intra-sexual competition between females for mates, coupled with high benefits associated with maintaining exclusive access to male care. The high level of intra-specific competition between females also seems to have led to the development of a novel vocal strategy in the eastern whipbird. Females not only replied to their partners but also to male intruders to form precise extra-pair duets which were similar in structure to pair duets. Simulated intrusions suggested that the rate of extra-pair duets produced was highest in the presence of a female rival. Thus, females may respond to males other than their partners as a means of type-matching and overlapping the songs of female rivals.
-
ItemThe function of female and male ornaments in the lovely fairy-wren( 2019)Ornaments like plumage colours or complex song are generally regarded as male traits that are shaped by sexual selection. By contrast, the factors that shape female elaborate traits have often been overlooked, though they are expressed in females across many taxa. Understanding how trade-offs and selective pressures shape female ornamentation is crucial for advancing our understanding of trait evolution. In this thesis, I investigate the form and function of female and male plumage colour and song in the Lovely fairy-wren (Malurus amabilis), a tropical species in which females and males are both highly colourful and vocal. This was investigated over three consecutive years and field seasons in Far North Queensland, Australia. My thesis research employed field observations, behavioural experiments, and genetic analysis, to test the adaptive function(s) and mechanisms for the evolution of female and male ornamental traits. I explicitly contrast females and males so that we can address, in the light of the abundant work done on males, how females may or may not differ from males. To provide context for the ornamental traits that are exhibited by this species, I first provide a comprehensive overview of the ecology and breeding biology of the Lovely fairy-wren, since a detailed description on the species natural history prior to this work was lacking. To understand the function of plumage colouration, I studied whether plumage colour in females and males is a signal and experimentally tested if it functions in a competitive context. Additionally, I assessed whether plumage colour is sexually selected, by examining its signalling content, costs (survival), and its relationship with reproductive and paternity success. Lastly, I investigated the song function, by describing female and male song structure and examining sex-specific variation in song rate across different contexts. I also used experimental data to examine female and male responses to simulated territorial intrusion. Overall this thesis provides insight into the form and function of both female and male plumage colours and song. First, it shows that visual and acoustic ornaments are important signalling components in different contexts, suggesting that female ornaments are not just a correlated genetic by-product of traits in males, and that selection favours female (and male) expression of traits. Second, the information conveyed by plumage colouration seems to be context-dependent in relation to the sex of the bearer: in males, it may follow the classical pattern of sexual selection, functioning in mate choice and male-male competition, while in females, plumage colours do not seem to be influenced by male choice, but function in same-sex competitive contexts. Third, it highlights that song has convergent functions in both sexes, as females and males have similar song structure and used song year-round in identical contexts for within-pair communication and joint territorial defence. The fact that females and males sing and have bright colours year-round in parallel with their territorial and breeding behaviour, suggests that individuals use their traits to maintain (sexual and non-sexual) resources. This work highlights the importance of studying and considering the fundamental differences in females and males, a necessary step for a realistic understanding of ornament expression, and contributes to the ongoing discussion on the evolution of elaborate female signal traits.
-
ItemPredicting ectotherm life cycles under a variable climate: physiological diversity of matchstick grasshopper eggs and their ecological and evolutionary implications( 2019)Understanding the processes underlying the phenology and distribution of species is a key problem in ecology. These relationships are important for predicting the responses to species to environmental change. Phenology and distribution are closely linked to climate and weather through the thermal dependence of life cycles. However, for many biodiverse taxa, like insects, we have a poor understanding of the mechanistic links between adaptive traits and how life cycles are adapted to seasonal and variable temperature patterns. Insect life cycles are synchronised with suitable climatic conditions at critical life stages, such as the egg stage. Variation in thermal sensitivity of development and dormancy are two mechanisms by which insects can generate adaptive life cycle phenotypes. Eggs, therefore, present a unique opportunity to link adaptive variation in traits with corresponding variation in life cycles and thermal environments to examine how life cycles are adapted to variable climates. To understand the adaptation of insect life cycles to variable climates, we require a mechanistic understanding of the interactions between adaptive developmental traits of eggs and variation in the thermal environment on adaptations. Our ability to test thermal adaptation in ectotherms is also limited by our ability to efficiently characterise thermal responses. In this thesis, I described how thermocyclers are an efficient means of characterising the thermal response of small ectotherms with enough precision and sample size. I then used the widely distributed, endemic and flightless Australian matchstick grasshopper genera Warramaba (Orthoptera: Morabidae) as a model system to examine the significance of variation in thermal responses at the egg stage for life cycles under a variable climate. I used a mechanistic modelling framework to tease apart developmental and environmental sources of variation in life cycles at the egg stage and simulate their consequences for phenology and distribution in the field. Matchstick grasshoppers showed remarkable diversity in developmental responses to temperature at the egg stage, primarily in the expression of dormancy. I found that diverse Warramaba life cycles are shaped by the interactions between such developmental variation and local environmental temperatures. I demonstrated that we can achieve a mechanistic understanding of life cycle adaptation by considering the evolution of temperature-dependent traits and the evolution of life history within the context of seasonal temperature cycles. Mechanistic models are powerful tools to investigate the sources of life cycle variation and their consequences for insect distribution and phenology. Such frameworks are directly transferrable to other socio-economically important or threatened species to understand how insects are adapted to local climatic conditions and predict responses to a changing climate.
-
ItemTesting the decline of the threatened New Holland Mouse (Pseudomys novaehollandiae)( 2019)Delineating the distribution of a threatened species is critical for identifying threats and guiding conservation management. The process is challenging, however, especially when a species is rapidly declining, and so changing its distribution. In this context, species distribution modelling (SDM) often lacks the precision needed to inform fine-scale management decisions, but on-ground surveys to test species’ distributions are time and resource intensive. The dilemma can be mitigated to some extent by careful examination of historical data, and optimal monitoring. The New Holland Mouse (NHM; Pseudomys novaehollandiae) is one of many Australian rodent species to have undergone drastic distributional declines since European invasion. Initially recorded in Victoria in 1970, by 2015 NHMs were thought to occur in only 3 of 12 historically occupied regions. I tested this decline with statistical rigour, using extensive Elliott and camera trapping surveys at >500 sites across Victoria. Combining my survey data with 48 years of others’ efforts, I evaluated the utility of standard Elliott trapping surveys and the efficacy of camera trapping for NHMs. I tested whether NHMs were where we would expect based on state-government threatened fauna SDMs, and whether the species’ purported early-successional fire association explained occurrence or abundance. I confirmed the species’ persistence in 5 of 12 historical regions – including regions where NHMs had not been detected in 5-21 years – and expanded the species’ known distribution in two regions. However, these finds can be attributed to a paucity of prior survey effort and were partnered with greater declines elsewhere. Elliott trapping surveys were often inadequate to provide statistical confidence in the species’ absence; camera trap surveys provide a viable alternative for distribution assessments. Standard state-government SDMs provided limited guidance as to the true distribution of NHMs and SDMs for declining species should be interpreted with caution. Time-since-fire did not explain the species’ occurrence and poorly explains abundance, though in certain locations inappropriate fire regimes are a threatening process. Predator control, habitat management, and careful reintroductions are key priorities for conservation of NHMs in Victoria.
-
ItemBiochemical mechanisms of biomineralization and elemental incorporation in otoliths: implications for fish and fisheries research( 2018)All vertebrates have small bioinorganic “earstones” in their inner ear labyrinth that are essential for hearing and balance. While otoliths play a vital anatomical role in fish, their true value to science is as biochronometers, largely due to their unique pattern of growth. Otoliths first form in embryo and continue to grow throughout the life of an individual, with a double-banded increment composed of a calcium carbonate-rich region and a protein-rich region being deposited daily. In addition to this, they are considered to be metabolically inert, and do not undergo remodelling or resorption. Consequently, otoliths are employed in a variety of ways in fish ecology. Firstly, an individual fish’s age and growth rate can be estimated through counting increments and measuring their widths. Secondly, analysis of increment trace element:calcium ratios, such as by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), can allow for the reconstruction of environmental histories, aiding in the determination of natal origin, movement, habitat use, diet and the impacts of climate change. The utility of specific trace elements as indicators of environmental change, however, is unclear as there is considerable uncertainty as to whether a given trace element is interacting with the mineral or protein components of an increment. This uncertainty is a consequence of otolith research having been largely focussed upon either microstructure or inorganic chemistry, with very few studies on the protein-rich regions of the otolith. As a result, very little is understood about the biochemical mechanisms of biomineralization or trace element incorporation. This is important, as the mechanisms that govern otolith formation and growth underpin the assumptions made in traditional increment analyses. In this thesis, I initially undertook a systematic review of all the literature pertaining to otolith biochemistry, revealing the significant gaps that exist in otolith biochemistry as a discipline. Importantly, I determined that fewer than a score of otolith proteins had been identified – a stark contrast to the hundreds or thousands of proteins that have been identified in comparable biomineral systems such as enamel or bone. Working on black bream (Acanthopagrus butcheri), an extensively studied species endemic to southern Australia, I used size exclusion chromatography coupled with ICP-MS to determine the trace element:protein interactions in endolymph, the inner ear fluid that otoliths are submerged in, and the source of all of its constituents. In this study, I assayed 22 elements, and determined that 12 were solely present in a protein-bound form, 6 were present as free ions, and 4 were present in both forms. This allowed me to make recommendations as to their utility in environmental reconstructions. In my next study, I created a unique, multi-disciplinary workflow that combined transcriptomics with proteomics. In this study, I sequenced the transcriptome of the black bream inner ear and used this to identify proteins from the separated organic phase of otoliths and endolymph from wild caught adult black bream. This resulted in the discovery of hundreds of previously unknown proteins, providing new insights into the likely biochemical mechanisms involved in otolith formation and growth. In my final study, I tested the utility of trace element ratios in environmental reconstructions. Specifically, I compared the ability of different cluster analysis approaches to resolve spatial and temporal differences in the likely spawning and larval nursery habitats of juvenile black bream in the Gippsland Lakes, Australia. The results from my thesis have allowed me to make recommendations as to the utility of trace elements in environmental reconstructions and have revealed exciting new avenues of research that fuse ecology and biochemistry.
-
ItemNovel gene therapy for the treatment of diabetes-induced heart failure( 2018)People with diabetes are at risk of developing myocardial abnormalities known as diabetic cardiomyopathy. This is characterised by diabetes-induced left-ventricular (LV) impairment, which develops independent of hypertension, coronary artery or valvular heart disease, leading to an increased risk of heart failure. To date, there is still no effective or specific treatment for diabetic cardiomyopathy. Hence, the overall aim of my thesis was to investigate the therapeutic potential of targeting two distinct novel pathways, the phosphoinositide 3-kinase (PI3K)p110α axis and the hexosamine biosynthesis pathway (HBP)/O-GlcNAcylation, in the setting of diabetic cardiomyopathy. PI3K(p110α) is a lipid kinase that regulates several physiological functions, including membrane trafficking, adhesion, actin rearrangement, cell growth, and survival. Recent findings from our laboratory and others have highlighted that PI3K(p110α) is cardioprotective in a range of different cardiac pathologies. In Chapter 3, I investigated whether cardiac-directed PI3K(p110α) gene therapy ameliorates diabetic cardiomyopathy in a mouse model of type-1 diabetes (T1D) in vivo. I revealed that administration of recombinant adeno-associated virus-6 constitutively-active PI3K(p110α) (rAAV6-caPI3K) attenuated diabetic cardiomyopathy, even when administered after the initial manifestation of LV diastolic dysfunction. I then proceeded to investigate the cardioprotective effects of rAAV6-caPI3K in the more clinically-prevalent type-2 diabetes (T2D) setting. In Chapter 4, I elucidated that restoration of cardiac PI3K(p110α) activity, through the administration of rAAV6-caPI3K gene therapy, attenuates T2D-induced cardiomyopathy, together with limiting ROS generation. In comparison to the cardioprotective nature of PI3K(p110α), the HBP and subsequent protein O-GlcNAcylation have been implicated in the development of diabetic cardiomyopathy. The generation of β-N-acetylglucosamine (O-GlcNAc) from HBP is a substrate for the post-translational protein modification (PTM) called O-GlcNAcylation. Two specific enzymes regulate the addition and removal of O-GlcNAc modification; O-GlcNAc transferase (OGT) catalyses the addition of GlcNAc to proteins and O-GlcNAc-ase (OGA) facilitates its removal. In Chapter 5, I aimed to elucidate the effect of cardiac manipulation of O-GlcNAcylation in the setting of diabetes-induced cardiac dysfunction in vivo. I demonstrated here that a cardiac-selective increase in OGT (via rAAV6-OGT gene delivery), the enzyme responsible for O-GlcNAcylation, is sufficient to drive cardiac dysfunction and remodelling, resembling that seen in diabetic cardiomyopathy. In contrast, increasing cardiac OGA (via rAAV6-OGA gene delivery), the enzyme responsible for the removal of the O-GlcNAc moiety, attenuates several characteristics of diabetic cardiomyopathy, likely at least in part through the improvement of mitochondrial function. Finally, in Chapter 6 I investigated the impact of O-GlcNAcylation on the PI3K(p110α), pathway and the effect of PI3K(p110α) gene therapy on HBP signalling. I elucidated that PI3K(p110α) can negatively regulate consequences of the HBP and O-GlcNAcylation as part of its cardioprotective actions in diabetic cardiomyopathy, while HBP/O-GlcNAcylation inhibits PI3K(p110α)-mediated signalling, likely contributing to the ability for this pathway to exert cardiac impairments. In conclusion, data from this thesis reveal that gene therapies targeting PI3K(p110α) and HBP/O-GlcNAcylation are viable therapeutic targets for diabetic cardiomyopathy. These results hence provide a basis for pursuing gene therapy for the treatment of diabetes-induced heart failure.