Functional resilience of mutually repressing motifs embedded in larger regulatory networks

Elucidating the design principles of regulatory networks driving cellular decision-making has important implications in understanding cell differentiation and guiding the design of synthetic circuits. Mutually repressing feedback loops between 'master regulators' of cell-fates can exhibit multistable dynamics, thus enabling multiple 'single-positive' phenotypes: (high A, low B) and (low A, high B) for a toggle switch, and (high A, low B, low C), (low A, high B, low C) and (low A, low B, high C) for a toggle triad. However, the dynamics of these two network motifs has been interrogated in isolation in silico, but in vitro and in vivo, they often operate while embedded in larger regulatory networks. Here, we embed these network motifs in complex larger networks of varying sizes and connectivity and identify conditions under which these motifs maintain their canonical dynamical behavior, thus identifying hallmarks of their functional resilience. We show that the in-degree of a motif - defined as the number of incoming edges onto a motif - determines its functional properties. For a smaller in-degree, the functional traits for both these motifs (bimodality, pairwise correlation coefficient(s), and the frequency of 'single-positive' phenotypes) are largely conserved, but increasing the in-degree can lead to a divergence from their stand-alone behaviors. These observations offer insights into design principles of biological networks containing these network motifs, as well as help devise optimal strategies for integration of these motifs into larger synthetic networks.

Designing a Co-creation System for the Development of Work-process-related Learning Material in Manufacturing

The increasing digitalization and automatization in the manufacturing industry as well as the need to learn on the job has reinforced the need for much more granular learning, which has not yet impacted the design of learning materials. In this regard, granular learning concepts require situated learning materials to support self-directed learning in the workplace in a targeted manner. Co-creation approaches offer promising opportunities to support employees in the independent design of such situated learning materials. Using an action-design research (ADR) approach, we derived requirements from co-creation concepts and practice by conducting focus group workshops in manufacturing and vocational training schools to develop design principles for a co-creation system that supports employees through the creation process of work-process-related learning material. Consequently, we formulate four design principles for the design of a collaborative learning and qualification system for manufacturing. Using an innovative mixed methods approach, we validate these design principles and design features to demonstrate the success of the developed artifact. The results provide insights regarding the design of a co-creation system to support learners in the co-creation of learning material with the consideration of cognitive load (CL). Our study contributes to research and practice by proposing novel design principles for supporting employees in peer creation processes. Furthermore, our study reveals how co-creation systems can support the collaborative development of learning materials in the work process.