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Biology subjects

Fawcett, A.

Publications and source records attributed to Fawcett, A..

2 recordsLinked to original sources

Evaluating a structured expert elicitation approach for adaptive conservation: Lessons from five years in practice

Threatened species management relies on Ex ante estimates of species responses to different interventions to generate meaningful predictions. Structured expert elicitation is often used to generate these estimates, but comparisons of these expert-predicted outcomes with observed results are rare. This study aims to evaluate the utility of expert elicitation for adaptive management in the New South Wales Saving our Species (SoS) program in Australia by revisiting six species management plans that were generated from bespoke structured elicitation guidelines five years prior. Each species management plan included a defined scope, conceptual model, monitoring indicators and estimated response to management curves under different scenarios. Experts reviewed the conceptual models after five years of management and monitoring and compared the predicted response to management with observed monitoring data. In three of the six case studies, observed outcomes closely matched predictions. Where predictions diverged, factors such as unanticipated new threats and unexpected responses to interventions contributed to discrepancies. However, in all cases, the structured approach provided a clear logic for planning, enabling managers to systematically refine their understanding. The conceptual models and response curves proved valuable for collaboration, communication, and generating hypotheses for unexpected results. This work demonstrates the value of the bespoke guidelines in supporting adaptive management processes, strengthening the knowledge base for threatened species conservation while improving alignment between predictions and real-world outcomes.

ecology↗

Selective degradation of BRD9 by a DCAF16-recruiting targeted glue: mode of action elucidation and in vivo proof of concept

Prospective discovery of molecular glues degraders for a specific therapeutic target protein of interest is an emerging strategy in drug discovery. Modification of pre-existing ligands with fragments that can alter the protein surface can lead to the creation of novel compounds ( targeted glues) able to induce neo-interactions between the target and an E3 ligase, resulting in targeted protein degradation. By screening a library of potential BRD9 targeted glue compounds, we have discovered a potent and selective, reversibly covalent BRD9 degrader, AMPTX-1. Co-immunoprecipitation-mass spectrometry experiments demonstrated that cell treatment with AMPTX-1 induces selective recruitment of BRD9 to the E3 ligase DCAF16. Degradation is dependent on the engagement of the surface Cys58 of DCAF16 and formation of a covalent adduct to DCAF16 is facilitated by the ternary complex formation with BRD9. BRD9 degradation is achieved in vivo after oral dosing, demonstrating that covalent recruitment of DCAF16 is a viable strategy for targeted protein degradation and can be achieved with drug-like, orally bioavailable compounds with promising in vivo activity.

biochemistry↗