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.

Sharing the vision: representing the matters of concern for design-led fledgling companies in Scotland

Design is being performed on an ever-increasing spectrum of complex practices arising in response to emerging markets and technologies, co-design, digital interaction, service design and cultures of innovation. This emerging notion of design has led to an expansive array of collaborative and facilitation skills to demonstrate and share how such methods can shape innovation. The meaning of these design things in practice can't be taken for granted as matters of fact, which raises a key challenge for design to represent its role through the contradictory nature of matters of concern. This paper explores an innovative, object-oriented approach within the field of design research, visually combining an actor-network theory framework with situational analysis, to report on the role of design for fledgling companies in Scotland, established and funded through the knowledge exchange hub Design in Action (DiA). Key findings and visual maps are presented from reflective discussions with actors from a selection of the businesses within DiA's portfolio. The suggestion is that any notions of strategic value, of engendering meaningful change, of sharing the vision of design, through design things, should be grounded in the reflexive interpretations of matters of concern that emerge.