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Intracellular protein technology

W. Xu, P. Colas, and R. Brent*

Department of Molecular Biology, Massachusetts General Hospital,
Department of Genetics, Harvard Medical School,
and Molecular Sciences Institute
50 Blossom Street, Boston, Massachusetts 02114

This is an abstract for a talk to be given at the Fifth Foresight Conference on Molecular Nanotechnology.

The lab develops and uses rough-and-ready protein engineering techniques to make complex protein constructions bound upstream of reporter genes in living cells. We are using the resulting intracellular protein machinery to assign function to genes. Recently, we realized that we could describe relationships between gene products detected by such machinery in symbolic-logical terms, and used this symbolic-logical description to guide construction of intracelluar protein machinery that registers relatively complex relationships among gene products. Cells that contain the protein-based intracellular hardware to register such complex genetic relationships can identify important subclasses of proteins, including natural and synthetic proteins that recognize disease state mutant gene products but not the healthy variants.

By performing logical operations on the phenotypic outputs of cells that contain this hardware, we can distinguish among different models of protein function in genetic networks. This information is simple but often informative, and the fact that it is obtained from self-replicating cells makes it possible for us to plan to obtain it systematically from entire genomes.

Perhaps as significant for the purposes of this meeting, we show that cells that register such relations can perform logical operations on protein inputs, and thus that these cells may constitute a first step toward the construction of inexpensive, self-replicating (but slow) logical devices.

*Corresponding Address:
Roger Brent, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114, email:
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