Research at the Intersection of the Physical and Life Sciences (2010) / Chapter Skim
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5 Enabling Technologies and Tools for Research
5 Enabling Technologies and Tools for Research
Pages 51-68
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From page 51... ...
These tools have enabled the study of the structures and dynamics that drive biological systems, and the progress has been spectacular. However, there still is much to be learned at all length scales of biological systems, from nanosized organisms to global ecosystems, and suitable tools and technologies will be critically important in studying those systems over the next 20 years.
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From page 52... ...
In this metaphor, two molecules associate when they have complementary shapes. Complementary shapes maximize van der Waals interactions and make it possible to associate complementary electrostatic charges.
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From page 53... ...
No doubt top-down approaches to designing new tools will continue to be extraordinarily useful, but the scope of what can be accomplished through such tools is limited. Recently, bottom-up technology -- whereby self-assembly of nanostructures can be used to create new materials and to perform functions that can probe biological systems -- has started to allow collecting much more useful data for understanding these and other complex biological issues (Whitesides and Grzybowski, 2002)
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From page 54... ...
Dilute aqueous solutions were historically used as a model medium because the tools to do single-cell studies simply did not exist originally. When molecular biology began, proteins were very difficult to obtain in pure form, and analytical systems were crude.
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From page 55... ...
a single cell, biology depends on macromolecular assemblies. This dependence is apparent in the molecular mechanisms underlying gene expression, signal transduction, cell migration, cell organization, and cell division.
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From page 56... ...
For example, multifunctional ligands could serve as scaffolds to effect signaling pathways not known to exist in nature or could endow cells with unexpected plasticity. Because modular protein assemblies are essential cellular control elements, myriad possibilities exist for using multifunctional ligands to manipulate cellular responses.
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From page 57... ...
Molecular dynamics is greatly limited in its time range and is forced to greatly simplify the interactions between the atoms. We need tools that can see, at the single-molecule level -- that is, at the sub-nanometer scale -- how biological molecules proceed in functional activities, without the use of probes.
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From page 58... ...
, which now are allowing the mapping of trajectories of individual molecules and organelles in live cells. Coherent, soft x-ray light sources also show great promise for studying bio logical systems and will probably provide high-resolution imaging in the middle of these underexplored but biologically critical length scales (Gibson et al., 2003)
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From page 59... ...
The time structure allows for very rapid exposures over timescales below the characteristic damage time structure of some samples. This has implications for both condensed matter and biological samples.
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From page 60... ...
THEORY AND SIMuLATIONS The diverse sizes and compositions of the heterogeneous molecules synthesized in biological environments generate a multitude of correlated phenomena on time and length scales that cannot be described with present analytical and numerical techniques. The understanding of biological processes requires the development of new theoretical approaches, modeling algorithms, and accurate effective poten tials that bridge these scales.
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From page 61... ...
Figure 5-4 shows some examples of symmetries found in biology that resemble symmetries found in assemblies of charged molecules. Finally, concepts developed in condensed matter theory to describe how emergent phenomena arise should have much to contribute to any question where interactions between many constituents is important.
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From page 62... ...
Examples include virus structures, such as shown in the upper left, that have similar structural arrangements as obtained in models by the faceting of ionic shells into icosahedra, as seen in the lower left. Virians that assemble at bacte rial membranes, as shown in the upper right, show structural similarities to the results of models computing the optimal arrangement of charged stripes over a cylindrical fiber, shown in the lower right.
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From page 63... ...
The understanding of biological processes via computational methods requires force field development and coarse-grained approaches that include solvent effects within molecular dynamics, which could be developed by using physicalchemical models extended to accurately bridge length and timescales. For example, one of the main problems in computational protein folding is the question of timescales.
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From page 64... ...
COLLECTIvE DYNAMICS As has been emphasized in previous chapters, the behavior of an individual cell does not determine the behavior of a collection of cells. Studying the dynamics of single cells underlies studying the collective dynamics of tissue, the extraordinarily complex assembly of cells and connective components that results in the creation of high-order plants and animals.
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From page 65... ...
Yet, in spite of this ever-increasing emphasis on a small resource and its exploitation, we are also seeing dramatic changes in the coastal marine ecosystems because of our failure to understand and protect this region. There is an urgent need to develop satellite imaging technologies that give us detailed temperature, cell density, metabolite concentrations, dissolved oxygen levels,
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From page 66... ...
By compiling many MRI measurements of the polarized water in a biological sample and extracting information from those images about the rates at which water is diffusing and its preferred directional paths, tensor mappings of the water diffusion can be developed and used to generate very detailed images of the tissue being measured. The figure visualizes a DTI measurement of the human brain.
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From page 67... ...
Gulf Coast Summertime satellite observations of ocean color from MODIS/Aqua show very turbid waters, which may include large blooms of phytoplankton extending from the mouth of the Mississippi River all the way to the Texas coast. When these blooms die and sink to the bottom, bacterial decomposition strips oxygen from the surrounding water, creating an environment in which it is very difficult for marine life to survive.
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From page 68... ...
Orland, 2007. Quantitative protein dynamics from dominant folding pathways, Physical Review Letters 99: 118102.
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