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The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research
localization of cellular substituents on the surface of such structures for enzymatic activity and specificity? Are the assemblages found within cells merely storage forms of the enzymes of interest, as is often speculated? Or is it possible that ordered arrays of reagents, in the nuclear matrix, on the surface of membranous vesicles or on the exposed surfaces of proteinaceous arrays provide the advantages of surface catalysis to biological systems?
In mature and developing organisms, local interactions among cells are mediated by complex local context. For example, in a developing Drosophila embryo, extremely high local concentrations of morphogens are formed and shape cell differentiation and mobility. Developing neurons will establish synaptic connections in response to subtle gradients. Understanding these cues requires not only identifying all the molecules involved but also developing analytical interpretive theories for their roles and testing those theories with, for example, high-definition and quantitative visualization techniques.
Understanding the activities and specificities of molecules and larger arrays within cells and tissues will require additional techniques from biophysics, microscopy, materials science, microfluidics, and computational biology. A particular need is the development of microscopy that bridges the gap between fluorescent light microscopy and electron microscopy. In addition to technological advances, the use of simulations of the movements of individual molecules (for example, using the Monte Carlo approach) and the development of theories that incorporate the nonequilibrium conditions of the cell could fuel new scientific advances.