Nutrigenomics and Beyond Informing the Future: Workshop Summary (2007) / Chapter Skim
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3 Scientific Session III: Systems Biology
3 Scientific Session III: Systems Biology
Pages 31-40
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From page 31... ...
The ultimate goal of systems biology is to create a computational model that describes the system of interest. Quoting Leroy Hood, one of the pioneers of systems biology, Cousins remarked that systems biology generally follows a pattern of first defining the elements of a system and then defining a mathematical model for the system, performing simulations with that model, comparing the simulations with what is known about the real system, refining the model based on those comparisons, and repeating those steps again and again to zero in on a model that accurately captures the behavior of the system itself.
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From page 32... ...
When glucose levels in the blood decrease, pancreatic beta cells produce glucagon, which stimu lates the liver to mobilize glycogen stores to release glucose into the bloodstream. When glucose levels rise, pancreatic alpha cells produce insulin, which inhibits glucose output from the liver and stimulates muscle and fat tissue to absorb glu cose from the blood.
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From page 33... ...
To address these questions, Kahn primarily relied on research from the Diabetes Genome Anatomy Project, whose goals are "to use mainly genomics and to some extent proteomics to define normal action of insulin on gene and protein expression in cells, mice, and in humans; to define the abnormalities of gene expression in insulin-resistant states; and to determine the role of genetic variation of insulin-signaling proteins in this." In short, the goals are to understand insulin action on a fundamental level and to use that understanding to pinpoint what goes wrong (and why) when insulin resistance develops.
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From page 34... ...
Ronald Kahn, used with permission, January 9, 2007. 3-1.eps gene expression or gene function and that these lead to more subtle phenotypes." As a result, the Kahn laboratory created mice that had heterozygous knockouts for both the insulin receptor (IR)
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From page 35... ...
Therefore, there are genes that can be viewed as being directly regulated by the insulin signal, for example, those that are changed in the MIRKO mouse, those that are changed in the diabetic animal but not in the MIRKO mouse, and those that are discordantly regulated between diabetes and insulin signaling (that is, the absence of insulin signaling causes an increase in gene expression, but the hyperglycemic state represses expression; in effect, the steady-state levels are not changed)
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From page 36... ...
Evaluation of the most well-characterized of metabolic disorders like obesity, type II diabetes, and the metabolic syndrome will require rethinking the entire nature of this system because not only can insulin directly regulate metabolism and gene expression in its target tissues, but the action of insulin is also affected tremendously by nutrients, the genetic background of the animal, and the nutritional state at the time of study. Only by dissecting all of these individual components will real understanding of the true control of gene expression in response to hormones and nutrients be achieved.
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From page 37... ...
Surprisingly, they can predict the outcome of adaptive evolution, which is quite a complicated biological process." Microbial reconstructions have also been used to study horizontal gene transfer and the evolution of a complex bacterial genome to a simple bacterial genome. Importantly, reconstructions have proven to be a valuable tool in filling the gaps in literature knowledge.
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From page 38... ...
It can be used, for instance, to study disease states of metabolism and determine how they differ from normal states or to perform computational experiments on the effects of various nutrients on the metabolic network. Perhaps most importantly, the reconstruction should serve as the basis for what Palsson hopes will become a rapidly expanding resource.
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From page 39... ...
Philbert explained that much of the power of nanotechnology comes from a bottom-up approach to constructing nanostructure devices, which makes it possible to create molecular assemblies with unique properties that can be manipulated with an unprecedented degree of control. An example of a practical nanostructure application is the use of zinc oxide nanoparticles in sunscreen.
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From page 40... ...
By flooding a cell with the PEBBLE nanosensors and then monitoring the cell under a microscope, investigators can observe the distribution of oxygen, nitric oxide, or other target molecules throughout the cell and monitor its evolution in time. With a little cleverness combined with a thorough knowledge of physics, chemistry, and cellular biology, it is possible to measure a great number of cellular metabolic activities, including changes in temperature, viscosity, and local magnetic and electric fields.
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