Nextgeneration Experimental Systems

To cope with increasing demands for comprehensive and accurate measurement, a set of new technologies and instruments needs to be developed that offers a higher level of automation and high-precision measurement.

First, dramatic progress in the level of automation of experimental procedures for routine experiments is required to keep up with increasing demands for modelling and system-level analysis. High-throughput experiments may turn into a labour-intensive nightmare unless the level of automation is drastically improved. Further automation of experimental procedures would greatly benefit the reliability of experiments, throughput, and total cost of the whole operation in the long run.

Second, cutting-edge technologies such as microfluid systems, nanotechnology, and femtochemistry may need to be introduced to design and build next-generation experimental devices. The use of such technologies will enable us to measure and observe the activities of genes and proteins in a way that is not possible today. It may also drastically improve the speed and accuracy of measurement with existing devices.

In those fields in which there are obvious needs, such as sequencing and proteo-mics, the above goals are already being pursued. Beyond the development of high-throughput sequencers using high-density capillary array electrophoresis, efforts are being made to develop integrated microfabricated devices that enable PCR and capillary electrophoresis in a single microdevice [29, 30]. Such devices not only enable miniaturization and precision measurements, but will also allow significant increases in the level of automation.

In the developmental biology of Caenorhabditis elegans, identification of cell lineage is one of the major issues that needs to be met to assist analysis of the gene regulatory network for differentiation. The first attempt to identify cell lineage was carried out entirely manually [31, 32] and required several years to identify the lineage of the wild type. Four-dimensional microscopy allows multilayer confocal images to be collected at constant time intervals, but lineage identification is not automatic. With the availability of exhaustive RNAi knockout C. elegans, high-throughput cell lineage identification is essential for exploring the utility of the exhaustive RNAi. Efforts are under way to fully automate cell lineage identification, as well as acquisition of three-dimensional nuclear position data [33], fully utilizing advanced image-processing algorithms and massively parallel supercomputers. Such devices meet some ofthe criteria mentioned earlier and provide comprehensive measurement ofcell positions with high accuracy. With automation, high-throughput data acquisition can be expected. If the project succeeds, it can be used to automatically identify the cell lineage of all RNAi knockout mutants for early embryogenesis. The technology may be augmented, but with major efforts, to automatically detect cell-cell contacts, protein localization, etc.

Combined with whole-mount in-situ hybridization and possible future single-cell expression profiling, these techniques may enable complete identification of the gene regulatory network of C. elegans in the near future.

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