A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery.

A network approach to overcoming barriers to market engagement for SMEs in energy efficiency initiatives such as the Green Deal

The Green Deal (GD) was launched in 2013 by the UK Government as a market-led scheme to encourage uptake of energy efficiency measures in the UK and create green sector jobs. The scheme closed in July 2015 after 30 months due to government concerns over low uptake and industry standards but additional factors potentially contributed to its failure such as poor scheme design and lack of understanding of the customer and supply chain journey. We explore the role of key delivery agents of GD services, specifically SMEs, and we use the LoCal-Net project as a case study to examine the use of networks to identify and reduce barriers to SME market engagement. We find that SMEs experienced multiple barriers to interaction with the GD such as lack of access to information, training, and confusion over delivery of the scheme but benefited from interaction with the network to access information, improve understanding of the scheme, increasing networking opportunities and forming new business models and partnerships to reduce risk. The importance of SMEs as delivery agents and their role in the design of market-led schemes such as the GD are discussed with recommendations for improving SME engagement in green sector initiatives.

Does a peer model’s task proficiency influence children’s solution choice and innovation?

The current study investigated whether 4- to 6-year-old children’s task solution choice was influenced by the past proficiency of familiar peer models and the children’s personal prior task experience. Peer past proficiency was established through behavioral assessments of interactions with novel tasks alongside peer and teacher predictions of each child’s proficiency. Based on these assessments, one peer model with high past proficiency and one age-, sex-, dominance-, and popularity-matched peer model with lower past proficiency were trained to remove a capsule using alternative solutions from a three-solution artificial fruit task. Video demonstrations of the models were shown to children after they had either a personal successful interaction or no interaction with the task. In general, there was not a strong bias toward the high past-proficiency model, perhaps due to a motivation to acquire multiple methods and the salience of other transmission biases. However, there was some evidence of a model-based past-proficiency bias; when the high past-proficiency peer matched the participants’ original solution, there was increased use of that solution, whereas if the high past-proficiency peer demonstrated an alternative solution, there was increased use of the alternative social solution and novel solutions. Thus, model proficiency influenced innovation.