ChOICE · Chance Or Intentional: Cellular decisions Explored

Cells are incredibly complex out-of-equilibrium systems that constantly react to changing environments in an efficient and strategic manner. As a consequence, it is necessary for cells to make fast and accurate decisions about their functional roles to fit their needs both at short and long timescales. Throughout the decision-making process fluctuations in protein levels, called noise, play a pivotal role. A high amount of noise allows probabilistic decision-making and enhances fitness when cells find themselves in variable environments. However, noise can be detrimental for commitment to cellular decisions, requiring cells to implement strategies to minimise noise when it is unfavourable. Due to the prevalence and importance of cellular-decision making in healthy and pathogenic cells, it is highly important to identify the molecular events that drive and modulate noise throughout the decision-making process. This requires single-cell approaches that identify the molecular drivers, modulators, and enforcers of cellular decisions at both short and long timescales.In Chance Or Intentional: Cellular decisions Explored, we will identify the molecular drivers of cellular decision, the feedback architectures that modulate commitment to decisions, and physical properties that enforce memory of decisions. We propose an ambitious research program that maps the mechanisms underlying cellular decision-making by combining single-molecule imaging, single-cell sequencing, and time-lapse microscopy with mathematical models. The results will provide a much-needed quantitative characterization of the decision-making process at three distinct timescales. Since protein noise has been associated with various pathological conditions, including infections and cancer, the results from ChOICE will have a wide-ranging impact.