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4 Common Themes at the Intersection of Biological and Physical Sciences
Pages 30-50

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From page 30...
... Today, 60 years later, the challenge in studying living matter is to produce a framework for understanding the highly organized and information-rich biological structures that are engaged not only in the acquisition and conversion of metabolic energy but also in the acquisition and transfer of information. Unraveling the complexity of living systems is a challenge that requires not only the creative application of ideas and tools for interacting systems but also the development of new conceptual and mathematical frameworks that can incorporate informa 0
From page 31...
... Although we understand the basic laws governing these forces, using these laws to reliably predict specific, complex intermolecular interactions and tracking the effect of the intermolecular interaction to the behavior of a whole organism remain a challenge. To deal with some of these challenges, ab initio approaches are now frequently complemented by data-driven bioinformatics that analyze and compare empirical data to untangle the interactions between numerous related interacting pairs of molecules.
From page 32...
... . The design of engineered zinc fingers for practical applications requires a thorough understanding of the interaction "code" that defines transcription factor/DNA binding specificity.
From page 33...
... This family of signaling proteins controls the regulation of diverse processes, ranging from the expression of genes required for a yeast cell to adapt to the carbon sources in the environment to the transcription of proto-oncogenes in the development of cancer, to programmed cell death. Over a dozen MAP kinase family members have been discovered in mammals alone.
From page 34...
... . Experimental data and modeling suggest that chemotaxis recep tors are poised to rapidly change signaling strength and the receptors cluster to amplify the signal.
From page 35...
... As a result of work by both physical scientists and life scientists, we now know that in chemotaxis, bacterial cells must respond rapidly to small, differential changes in ligand concentration. Consistent with this, chemotaxis receptors are poised to rapidly change signaling strength, spending nearly half their time in the on state.
From page 36...
... Insight into dynamic behavior cannot be achieved without recourse to quantitative analysis. The latter provides an immediate connection to physical sciences and mathematics, fields that have developed powerful tools and concepts for studying deterministic and stochastic dynamical processes.
From page 37...
... . Energy landscape ideas provide powerful insight into the dynamics of complex biological molecules that catalyze chemical reactions or, in the case of molecular motors, perform mechanical work.
From page 38...
... involving sequential binding and unbinding of the motor heads to the micro tubule along which the motor "walks." What is the mechanism coordinating large changes in the conformation of different domains -- the physical "steps" that the motor takes -- with the chemical activity that powers the motion? Recent modeling efforts have approached this problem using the landscape ideas for protein folding and have identified the critical role of the intermediate state (high lighted in the figure)
From page 39...
... The model network is presented with a cue at a 180-degree angle at time C and retains a memory in the form of a stable "bump" state during a delay period D until Figure 4-4.eps the memory is recalled at time R The action potential firing pattern and spike rate histogram of an individual model neuron in the network (bottom right)
From page 40...
... The basic mechanism is that a neural system becomes attracted to one of multiple stable states, which can be thought of as local minima in an energy landscape. An example is spatial work ing memory in a cortical network (Compte et al., 2000)
From page 41...
... . To illustrate the vast range of dynamical phenomena and the vast range of tem FIGURE 4-5 Molecular Noise and Stochasticity of the Cell Single-cell imaging of genetically encoded fluorescent proteins (CFP and YFP, shown in orange and the darker green color channels)
From page 42...
... As with many of the great challenges in the environmental end of science at the interface of the biological and physical sciences, the unknowns in the global nitro gen cycle involve processes that interact across a vast range of temporal and spatial scales. Understanding nitrogen fixation or gas loss depends on effectively integrat
From page 43...
... The committee reiterates that some of the grandest challenges in science involve understanding how emergent properties link physical and biological properties, from the molecular to the global scale, and how their properties can be managed to achieve specific effects. SELF-ORGANIzATION AND SELF-ASSEMBLY In physics, crystalline structure is explained in terms of energy and thermodynamics, and the dynamics of crystallization can create a multitude of forms, as, for example, in snowflakes.
From page 44...
... may help to uncover some of the fundamental principles of living matter. A fascinating example of molecular self-assembly in biology is provided by the bacterial flagellar motor (Chevance and Hughes, 2008)
From page 45...
... These fundamental aspects of morphogenesis are controlled by the genetically determined molecular interaction networks of the type mentioned above. Yet, morphogenesis ultimately involves the physical organization of tissues.
From page 46...
... The answer had to wait until molecular genetic and fluorescent imaging tech niques were developed, thereby allowing investigators to determine the distribution and transport of auxin, a plant hormone promoting leaf primordia growth in the shoot apical meristem (SAM)
From page 47...
... The model for phyllotactic pattern formation is similar in spirit, although not in letter, to the Turing model in providing a bridge between the molecular and morphological scales. The phyllotactic model is now being used in close collaboration with experiment to further explore the dynamics of SAM growth and its regulation.
From page 48...
... Panel (B) shows phyllotaxis in a physical system: a phyllotactic pattern generated by sequential addition of ferrofluid droplets in the center of a dish with a slow radial flow of viscous fluid.
From page 49...
... Klug, A., 2005. The discovery of zinc fingers and their development for practical applications in gene regulation, Proceedings of the Japan Academy Series B-Physical and Biological Sciences 81: 87-102.
From page 50...
... Block, 2000. Force production by single kinesin motors, Nature Cell Biology 2: 718-723.


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