Modelling the intracellular NF-KB signalling pathway

NF-nB is a transcription factor which is central to the regulation of genes involved in inflammatory and immune responses. Understanding the operation of NF-KB and its associated intracellular signalling pathway is essential in order to control a wide range of chronic inflammatory diseases, including asthma and rheumatoid arthritis. Abnormalities in the pathway are present in a variety of human cancersa nd may also affect the pathogenesiso f Alzheimer's disease. Computational modelling of the signalling pathway is necessary to overcome the practical limitations of biological experiments and to facilitate a more comprehensive understanding of the system. The thesis begins by outlining existing understanding of the NF-rdB signalling pathway, which in conjunction with a review of modelling methods is used to inform a different approach to model the pathway, using computational agents to represent individual molecules and receptors. The agent-based model is tested with well-understood chemical reactions before being used to describe the pathway. This provides a good appreciation of the system as a whole, offering a detailed description of events at every step in the pathway and allowing investigation of stochastic, spatial and structural parameters. The modelling process and simulation help to provide a prediction about the role of actin filaments of the cytoskeleton in regulating the unstimulated pathway; this is quantitatively validated by biological experiment. The effect of cell shape on the pathway is also investigated

Estimating the effect of nitrogen fertilizer on the greenhouse gas balance of soils in Wales under current and future climate

This work was supported by a Grant from the Welsh Government (Glastir Monitoring and Evaluation Project—GMEP).Peer reviewedPublisher PD

Can biogas digesters help to reduce deforestation in Africa?

Acknowledgements The authors are grateful for financial support for this work in part from the UK Department for International Development (DFID) New and Emerging Technologies Research Call, and in part from the EU under the REDD-ALERT (Reducing Emissions from Deforestation and Degradation from Alternative Land Uses in Rainforests of the Tropics) project, Grant agreement number 226310. The authors thank Dr Hoang Viet Anh, Dr Suyanto and Mr. Gamma Galudra for their input on the manuscript.Peer reviewedPostprin

Agent-based modeling of diversity, new information and minority groups in opinion formation

Understanding the decentralized formation of public opinion is increasingly important to communication research. Although many key determinants cannot be observed empirically, we argue they can be explored through theoretical modeling. Building on an existing agent-based model of opinion dynamics, our study introduces more complex, but theoretically interesting and realistic, agent behavior. We model distinct opinion tendencies which represent individuals’ diversity of belief, as well as external influences such as new information. Diversity increases the extremity of opinion in simulated consensus, radicalization and polarization. Simulation of new information demonstrates the ability of a minority group to shift majority opinion significantly in the long term, even with transient changes in behavior. Opposing minority groups do not counteract each other when their actions are delayed and may in fact amplify the original effect. We argue that modeling can help researchers and other stakeholders understand how these outcomes could arise in the real world, and thereby explore potential mitigations or exploitations

Multi-copy genes that enhance the yield of mammalian G protein-coupled receptors in Escherichia coli

Low yields of recombinant expression represent a major barrier to the physical characterization of membrane proteins. Here, we have identified genes that globally enhance the production of properly folded G protein-coupled receptors (GPCRs) in Escherichia coli. Libraries of bacterial chromosomal fragments were screened using two separate systems that monitor: (i) elevated fluorescence conferred by enhanced expression of GPCR–GFP fusions and (ii) increased binding of fluorescent ligand in cells producing more active receptor. Three multi-copy hits were isolated by both methods: nagD, encoding the ribonucleotide phosphatase NagD; a fragment of nlpD, encoding a truncation of the predicted lipoprotein NlpD, and the three-gene cluster ptsN–yhbJ–npr, encoding three proteins of the nitrogen phosphotransferase system. Expression of these genes resulted in a 3- to 10-fold increase in the yields of different mammalian GPCRs. Our data is consistent with the hypothesis that the expression of these genes may serve to maintain the integrity of the bacterial periplasm and to provide a favorable environment for proper membrane protein folding, possibly by inducing a fine-tuned stress response and/or via modifying the composition of the bacterial cell envelope

PopFor : A new model for estimating poplar yields

Yield and soil data for this project has been supplied by Rainer Schlepphorst, Holger Hartmann and Dieter Murach from HNEE, Germany, from the BIODEM project. Soil water and groundwater data were supplied by Markus Schmidt, HNEE, Germany. We would like to thank Shell and the University of Aberdeen CLSM for funding this work with a studentship. The MiscanFor modelling was supported by UK NERC ADVENT (NE/1806209) and FAB-GGR (NE/P019951/1) project funding.Peer reviewedPostprin

Mapping the global potential exposure of soaring birds to terrestrial wind energy expansion

The wind energy sector is steadily growing, and the number of wind turbines is expected to expand across large areas of the globe in the near future. While the development of wind energy can contribute to mitigating climate change, it also poses challenges to wildlife, particularly birds, due to increased collision risk with wind turbines. Here we quantify and map potential conflicts between the potential for wind energy development and the distribution of terrestrial soaring birds. We explore the relationship between species traits (including body mass, migration ecology and extinction risk) and exposure to potential wind energy development, and identified areas of potential conflict between wind power production and soaring bird conservation. We considered the full range of each species, as well as separately analyzing the breeding, non-breeding and passage ranges for migratory species. We show that exposure to potential wind energy development is similar for soaring and non-soaring bird species. Within different parts of the range of soaring bird species, passage distributions have significantly higher potential for wind energy development than the full, breeding or non-breeding ranges. Moreover, exposure to potential wind energy development was higher within the ranges of heavier soaring bird species and those that are migratory. We show that areas of conflict between soaring bird conservation and potential wind energy development could be very large, particularly when the passage ranges of soaring bird species are considered. Such areas of potential conflict are largely unprotected. This highlights a risk for soaring birds from potential wind energy development wherever it is not carefully sited in order to minimise environmental impacts.Peer reviewe

Simulation of greenhouse gases following land-use change to bioenergy crops using the ECOSSE model : a comparison between site measurements and model predictions

This work contributes to the ELUM (Ecosystem Land Use Modelling & Soil Carbon GHG Flux Trial) project, which was commissioned and funded by the Energy Technologies Institute (ETI). We acknowledge the E-OBS data set from the EU-FP6 project ENSEMBLES (http://ensembles-eu.metoffice.com) and the data providers in the ECA&D project (http://www.ecad.eu).Peer reviewedPublisher PD

Crystallographic analyses illustrate significant plasticity and efficient recoding of meganuclease target specificity

The retargeting of protein-DNA specificity, outside of extremely modular DNA binding proteins such as TAL effectors, has generally proved to be quite challenging. Here, we describe structural analyses of five different extensively retargeted variants of a single homing endonuclease, that have been shown to function efficiently in ex vivo and in vivo applications. The redesigned proteins harbor mutations at up to 53 residues (18%) of their amino acid sequence, primarily distributed across the DNA binding surface, making them among the most significantly reengineered ligand-binding proteins to date. Specificity is derived from the combined contributions of DNA-contacting residues and of neighboring residues that influence local structural organization. Changes in specificity are facilitated by the ability of all those residues to readily exchange both form and function. The fidelity of recognition is not precisely correlated with the fraction or total number of residues in the protein-DNA interface that are actually involved in DNA contacts, including directional hydrogen bonds. The plasticity of the DNA-recognition surface of this protein, which allows substantial retargeting of recognition specificity without requiring significant alteration of the surrounding protein architecture, reflects the ability of the corresponding genetic elements to maintain mobility and persistence in the face of genetic drift within potential host target sites

Global change synergies and trade-offs between renewable energy and biodiversity

Reliance on fossil fuels is causing unprecedented climate change and is accelerating environmental degradation and global biodiversity loss. Together, climate change and biodiversity loss, if not averted urgently, may inflict severe damage on ecosystem processes, functions and services that support the welfare of modern societies. Increasing renewable energy deployment and expanding the current protected area network represent key solutions to these challenges, but conflicts may arise over the use of limited land for energy production as opposed to biodiversity conservation. Here, we compare recently identified core areas for the expansion of the global protected area network with the renewable energy potential available from land-based solar photovoltaic, wind energy and bioenergy (in the form of Miscanthusxgiganteus). We show that these energy sources have very different biodiversity impacts and net energy contributions. The extent of risks and opportunities deriving from renewable energy development is highly dependent on the type of renewable source harvested, the restrictions imposed on energy harvest and the region considered, with Central America appearing at particularly high potential risk from renewable energy expansion. Without restrictions on power generation due to factors such as production and transport costs, we show that bioenergy production is a major potential threat to biodiversity, while the potential impact of wind and solar appears smaller than that of bioenergy. However, these differences become reduced when energy potential is restricted by external factors including local energy demand. Overall, we found that areas of opportunity for developing solar and wind energy with little harm to biodiversity could exist in several regions of the world, with the magnitude of potential impact being particularly dependent on restrictions imposed by local energy demand. The evidence provided here helps guide sustainable development of renewable energy and contributes to the targeting of global efforts in climate mitigation and biodiversity conservation.Peer reviewe