Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation.

Inter-plant communication through mycorrhizal networks mediates complex adaptive behaviour in plant communities

Adaptive behaviour of plants, including rapid changes in physiology, gene regulation and defence response, can be altered when linked to neighbouring plants by a mycorrhizal network (MN). Mechanisms underlying the behavioural changes include mycorrhizal fungal colonization by the MN or interplant communication via transfer of nutrients, defence signals or allelochemicals. We focus this review on our new findings in ectomycorrhizal ecosystems, and also review recent advances in arbuscular mycorrhizal systems. We have found that the behavioural changes in ectomycorrhizal plants depend on environmental cues, the identity of the plant neighbour and the characteristics of the MN. The hierarchical integration of this phenomenon with other biological networks at broader scales in forest ecosystems, and the consequences we have observed when it is interrupted, indicate that underground ‘tree talk’ is a foundational process in the complex adaptive nature of forest ecosystems.

Anticipating future risk in social-ecological systems using fuzzy cognitive mapping: the case of wildfire in the Chiquitania, Bolivia

Understanding complex social-ecological systems, and anticipating how they may respond to rapid change, requires an approach that incorporates environmental, social, economic, and policy factors, usually in a context of fragmented data availability. We employed fuzzy cognitive mapping (FCM) to integrate these factors in the assessment of future wildfire risk in the Chiquitania region, Bolivia. In this region, dealing with wildfires is becoming increasingly challenging due to reinforcing feedbacks between multiple drivers. We conducted semi-structured interviews and constructed different FCMs in focus groups to understand the regional dynamics of wildfire from diverse perspectives. We used FCM modelling to evaluate possible adaptation scenarios in the context of future drier climatic conditions. Scenarios also considered possible failure to respond in time to the emergent risk. This approach proved of great potential to support decision-making for risk management. It helped identify key forcing variables and generate insights into potential risks and trade-offs of different strategies. All scenarios showed increased wildfire risk in the event of more droughts. The ‘Hands-off’ scenario resulted in amplified impacts driven by intensifying trends, affecting particularly the agricultural production. The ‘Fire management’ scenario, which adopted a bottom-up approach to improve controlled burning, showed less trade-offs between wildfire risk reduction and production compared to the ‘Fire suppression’ scenario. Findings highlighted the importance of considering strategies that involve all actors who use fire, and the need to nest these strategies for a more systemic approach to manage wildfire risk. The FCM model could be used as a decision-support tool and serve as a ‘boundary object’ to facilitate collaboration and integration of different forms of knowledge and perceptions of fire in the region. This approach has also the potential to support decisions in other dynamic frontier landscapes around the world that are facing increased risk of large wildfires.