The Fontana lab has two main goals. First, understand the dynamical processes that constitute and maintain biological organization in terms of interactions among molecular components. Second, identify those properties of a biological system that are necessary consequences of a particular level of organization, regardless of how that level is implemented in molecular terms. We bring this philosophy to experimental and theoretical approaches within three specific research directions aimed at understanding: (1) the integration of biological information — plasticity and learning in intracellular networks; (2) the disintegration of biological information — the process of aging (C.elegans model); and (3) the evolution of biological information — evolvability of phenotype.

1. Intracellular learning and memory (theory)
We still lack fundamental insight into the general principles whereby cells process and integrate information to make decisions. Many of the signals and signaling proteins involved in cell-fate decisions (such as differentiation, division, repair or apoptosis) are context-sensitive and involved in extensive (so-called) cross-talk. The response of a cell must thus depend not only on the signal but also on context and history. The group aims to develop a modeling framework for understanding how molecular networks achieve the plasticity and context-sensitive responses needed to process combinatorial signals.

2. The process of aging (experimental)
Our understanding of how lifespan depends on genetic and environmental factors has dramatically increased in the last decade. Perturbations in the function of single genes, such as the insulin receptor, can extend the lifespan of rodents, nematodes and insects. Findings like these indicate that molecular mechanisms for the determination of lifespan exist. These studies have focused on death as the endpoint of aging. Our lab instead focuses on the process of aging in terms of both temporal and organizational components. The long-term goal is to clarify the relationships between aging processes at different levels of structure (molecular, cellular, tissue, organismic), by observing physiological state over time. We are developing instrumentation to automate lifespan measurements, high-throughput microscopy imaging and precisely vary environmental conditions at the level of individual organisms, using microfluidics technology developed in collaboration with the Whitesides lab (Department of Chemistry & Chemical Biology).

3. Plasticity and Evolvability (theory and experimental)
The P.I. has been a pioneer in advancing the connection between plasticity (roughly, the environmentally induced change of phenotype at constant genotype) and variability (roughly, the mutational change of phenotype at constant environment) in the context of polymer (RNA) structure, predicting the possibility of a Baldwin effect at the molecular level. Others have independently hypothesized this connection in more complex situations, as in development. The significance of this connection derives from linking present system dynamics (“plasticity”) with future system structure (“variability”), where the former can be an easy target of selection and the latter co-varies with the former. The Fontana lab explores this connection through both theory and experiment.