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Gene Products. Each gene product is a protein
and understanding its 3-dimensional shape is key to understanding its
function in the microbial cell and the other proteins with which it interacts.
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Microbial Cell Research Thrusts Goal: Determine and characterize the minimum set of genes and corresponding gene products necessary to sustain a simple free-living microbial cell, express the genes to produce the relevant proteins, and determine their structure. Challenges: Once the entire genomic complement of a specific microbial cell has been determined, it should be possible to pare down this extensive set of genetic instructions to the minimum framework needed to direct sustainable growth under a defined set of favorable nutrient and environmental conditions. This is analogous to the situation in which a microbe is given all the basic building blocks for proteins; no longer required to synthesize each of these amino acid building blocks, the microbe still must implement the genetic instructions for assembling these building blocks into the appropriate enzymes that will carry out the basic life functions of the cell. Accelerated genomic information and enhanced biotechnological methods will enable scientists to streamline the traditional approach used in classical molecular genetics, in which laborious analyses are used to determine if specific genes are necessary or not under a favorable set of growth conditions. Once the minimum gene set has been determined, scientists must determine the functions of these essential genes. For the approximately 3 dozen or so microbial genomes completely sequenced to date, an astonishing 45% of the genes do not previously known genes; this means scientists do not have any clues as to the structures or functions of these novel genes. It is like having all the parts to a car spread out on a garage floor, but not knowing what half the parts are (or what they do). So one of the first imperatives is to characterize the unknown genes and their protein products. This can be approached in several ways, including targeted deletions of specific genes (to explore what functions are lost) and solving the physical structure of these gene products using high-resolution crystallographic or spectroscopic techniques. This latter approach is particularly powerful, as structural similarities between two proteins can often suggest functional relationships that scientists subsequently can verify by experimental means. The facilities of the DOE national laboratories (synchrotron sources, computational resources for protein structure prediction and comparisons) will be critically important to this thrust area. published 06/05/00 |
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