Comparative flux control through the cytoplasmic phase of cell wall biosynthesis

The introduction of antibacterial drugs in the middle of the last century heralded a new era in the treatment of infectious disease. However the parallel emergence of antibiotic resistance and decline in new drug discovery threatens these advances. The development of new antibacterials must therefore be a high priority. The biosynthesis of the bacterial cell wall is the target for several clinically important antibacterials. This extracellular structure is essential for bacterial viability due to its role in the prevention of cell lysis under osmotic pressure. Its principal structural component, peptidoglycan, is a polymer of alternating N-acetyl-glucosamine (GlcNAc) and N-acetyl muramic acid (MurNAc) residues crosslinked by peptide bridges anchored by pentapeptide stems attached to the MurNAc moieties. The biosynthesis of peptidoglycan proceeds in three phases. The first, cytoplasmic, phase is catalysed by six enzymes. It forms a uridine diphosphate (UDP) bound MurNAc residue from UDP-GlcNAc and attaches the pentapeptide stem. This phase is a relatively unexploited target for antibacterials, being targeted by a single clinically relevant antibacterial, and is the subject of this thesis. The Streptococcus pneumoniae enzymes were kinetically characterised and in silico models of this pathway were developed for this species and Escherichia coli. These models were used to identify potential drug targets within each species. In addition the potentially clinically relevant interaction between an inhibitor of and feedback loops within this pathway was investigated. The use of direct parameter estimation instead of more traditional approaches to kinetic characterisation of enzymes was found to have significant advantages where it could be successfully applied. This approach required the theoretical analysis of the models used to determine whether unique parameter vectors could be determined. Such an analysis has been completed for a broad range of biologically relevant enzymes. In addition a relatively new approach to such analysis has been developed

Humanitarianism at home: Exploring practitioners’ perspectives on the relevance of humanitarianism in Australia

Australia has faced various unprecedented challenges in recent years: the extended bushfire season of 2019–20, wide-spread and increasingly severe storms and flooding, and the grave health and socio-economic impacts of the global COVID-19 pandemic. Such events have prompted greater awareness of our shared vulnerability to disasters. They have also exacerbated food insecurity, homelessness, poverty, family violence, and increased the vulnerability of refugees and people seeking asylum in Australia. Where disasters and similar issues are identified in low-income countries, they are typically framed in terms of humanitarian need and may even be the subject of international humanitarian action. Why is it then, that the language and practices of humanitarianism are not ordinarily applied in Australian settings? What indeed is humanitarianism when it is not international? What, if anything, do international experiences of humanitarianism have to offer in Australian contexts? This paper describes a research program that has been prompted by these questions and shares some preliminary findings concerning the perspectives of Australian practitioners on the relevance of humanitarian values, knowledge, and practices in Australia

Equivariant homotopy commutativity for G = Cpqr

We investigate the combinatorial data arising from the classification of equivariant homotopy commutativity for cyclic groups of order G = Cp1···pn for pi distinct primes. In particular, we will prove a structural result which allows us to enumerate the number of N∞-operads for Cpqr, verifying a computational result

The role of omnivory in mediating metacommunity robustness to habitat destruction

Omnivores have long been known to play an important role in determining the stability of ecological communities. Recent theoretical studies have suggested that they may also increase the resilience of their communities to habitat destruction, one of the major drivers of species extinctions globally. However, these outcomes were obtained for minimal food webs consisting of only a single omnivore and its prey species, while much more complex communities can be anticipated in nature. In this study, we undertake a systematic comparative analysis of the robustness of metacommunities containing various omnivory structures to habitat loss and fragmentation using a mathematical model. We observe that, in general, omnivores are better able to survive facing habitat destruction than specialist predators of similar trophic level. However, the community as a whole does not always benefit from the presence of omnivores, as they may drive their intraguild prey to extinction. We also analyze the frequency with which these modules occur in a set of empirical food webs, and demonstrate that variation in their rate of occurrence is consistent with our model predictions. Our findings demonstrate the importance of considering the complete food web in which an omnivore is embedded, suggesting that future study should focus on more holistic community analysis

Habitat loss alters effects of intransitive higher-order competition on biodiversity: a new metapopulation framework

Recent studies have suggested that intransitive competition, as opposed to hierarchical competition, allow more species to coexist. Furthermore, it is recognized that the prevalent paradigm, which assumes that species interactions are exclusively pairwise, may be insufficient. More importantly, whether and how habitat loss, a key driver of biodiversity loss, can alter these complex competition structures and therefore species coexistence remain unclear. We thus present a new simple yet comprehensive metapopulation framework which can account for any competition pattern and more complex higher-order interactions (HOIs) among species. We find that competitive intransitivity increases community diversity and that HOIs generally enhance this effect. Essentially, intransitivity promotes species richness by preventing the dominance of a few species unlike hierarchical competition, while HOIs facilitate species coexistence through stabilizing community fluctuations. However, variation in species vital rates and habitat loss can weaken or even reverse such higher-order effects, as their interaction can lead to a more rapid decline in competitive intransitivity under HOIs. Thus, it is essential to correctly identify the most appropriate interaction model for a given system before models are used to inform conservation efforts. Overall, our simple model framework provides a more parsimonious explanation for biodiversity maintenance than existing theory

Ecotone formation induced by the effects of tidal flooding: A conceptual model of the mud flat-coastal wetland ecosystem

The boundary between mud flat and coastal wetland ecosystems is highly productive and a haven of considerable biodiversity. It is also embedded in a highly dynamic environment and can be easily destabilised by environmental changes, invasive species, and human activity. Thus, understanding the processes which govern the formation of this ecotone is important both for conservation and economic reasons. In this study we introduce a simple conceptual model for this joint ecosystem, which demonstrates that the interaction between tidal flooding and habitat elevation is able to produce an ecotone with similar characteristics to that observed in empirical studies. In particular, the transition from mud flat to vegetated state is locally abrupt, occurring at a critical threshold elevation, but, on broader spatial scales can occur over a range of elevations determined by the variability in high tide water levels. Additionally, the model shows the potential for regime shifts, resulting from periods of unusual weather or the invasion of a fast growing, or flood resistant, species

Habitat heterogeneity mediates effects of individual variation on spatial species coexistence

Numerous studies have documented the importance of individual variation (IV) in determining the outcome of competition between species. However, little is known about how the interplay between IV and habitat heterogeneity (i.e. variation and spatial autocorrelation in habitat quality) affects species coexistence at the landscape scale. Here, we incorporate habitat heterogeneity into a competition model with IV, in order to explore the mechanism of spatial species coexistence. We find that individual-level variation and habitat heterogeneity interact to promote species coexistence, more obviously at lower dispersal rates. This is in stark contrast to early non-spatial models, which predicted that IV reinforces competitive hierarchies and therefore speeds up species exclusion. In essence, increasing variation in patch quality and/or spatial habitat autocorrelation moderates differences in the competitive ability of species, thereby allowing species to coexist both locally and globally. Overall, our theoretical study offers a mechanistic explanation for emerging empirical evidence that both habitat heterogeneity and IV promote species coexistence and therefore biodiversity maintenance

Metacommunity robustness of plant–fly–wasp tripartite networks with specialization to habitat loss

Recent observations have found plant‐species‐specific fly‐host selection (i.e., specialization) of wasp parasitoids (wasps) in plant–fly–wasp (P–F–W) tripartite networks, yet no study has explored the dynamical implications of such high‐order specialization for the persistence of this network. Here we develop a patch‐dynamic framework for a unique P–F–W tripartite network with specialization observed in eastern Tibetan Plateau and explore its metacommunity robustness to habitat loss. We show that specialization in parasitoidism promotes fly species diversity, while the richness of both plant and wasp decreases. Compared to other two null models, real network structure favors plant species coexistence but increases the extinction risk for both flies and wasps. However, these effects of specialization and network structure would be weakened and ultimately disappear with increasing habitat loss. Interestingly, intermediate levels of habitat loss can maximize the diversity of flies and wasps, while increasing or decreasing habitat loss results in more species losses, supporting intermediate disturbance hypothesis. Finally, we observe that high levels of habitat loss initiate a bottom‐up cascade of species extinction from plants to both flies and wasps, resulting in a rapid collapse of the whole tripartite networks. Overall, this theoretical framework is the first attempt to characterize the dynamics of whole tripartite metacommunities interacting in realistic high‐order ways, offering new insights into complex multipartite networks

A patch-dynamic metacommunity perspective on the persistence of mutualistic and antagonistic bipartite networks

The structure of interactions between species within a community plays a key role in maintaining biodiversity. Previous studies have found that the effects of these structures might substantially differ depending on interaction type, for example, a highly connected and nested architecture stabilizes mutualistic communities, while the stability of antagonistic communities is enhanced in modular and weakly connected structures. Here we show that, when network dynamics are modelled using a patch-dynamic metacommunity framework, the qualitative differences between antagonistic and mutualistic systems disappear, with nestedness and modularity interacting to promote metacommunity persistence. However, the interactive effects are significantly weaker in antagonistic metacommunities. Our model also predicts an increase in connectance, nestedness and modularity over time in both types of interaction, except in antagonistic networks where nestedness declines. At steady state, we find a strong negative correlation between nestedness and modularity in both mutualistic and antagonistic metacommunities. These predictions are consistent with the structural trends found in a large dataset of real-world antagonistic and mutualistic communities