Genes versus molecules

COMPARATIVE DRUG DEVELOPMENT OF PROTEINS AND GENES VERSUS SMALL MOLECULES... 

Fig. 28.2. The left panel shows the effective potential for a simple gene switch analogous to that shown in Fig. 28.1. AC is a variable that scales with the protein number. gives the value of the number of transcription factor molecules needed (at equilibrium) to give an equal likelihood of the site being occupied or not. The right panel shows the demarcation lines for two-state switch behavior (for large o) and versus one-state averaged behavior for small cu or x )...

Fig. 28.4. The apparent renormalized law of mass action for a gene switch is shown in the outer panel. The probability of the gene being off versus average population of transcription factor is shown. The Shea-Ackers curve is the conventional macroscopic law of mass action. Single-molecule physical chemistry reigns ...

The so-called resistant strains, however, show a different response to mercury exposure. These resistant strains also show an increase in MHC expression molecules on B-cells, but this response is extremely short-lived, and increases in serum IgE were not observed (Dubey et al. 1991a Prouvost-Danon et al. 1981). The difference in the responses of the so-called resistant and susceptible strains may be found in the activation of Thl cells and the increase in secretion of -interferon by the Thl cells of resistant animals (van der Meide et al. 1993). The susceptible strains do not show an increase in -interferon production with mercury exposure. Because -interferon inhibits the proliferation of Th2 cells, the absence of this response in the susceptible strains may allow the Th2 cell-stimulated production of autoantibodies to occur, whereas in the resistant strains the production of antibodies is curtailed. Thus, differences in the activation of Thl versus Th2 cells may underlie the differences in susceptibility of various individuals. Studies using in-bred strains of mice and rats have determined that the susceptibility to the different immune reactions is governed by both MHC genes as well as other genes (Aten et al. 

Fig. 6-1 Classical genetics versus chemical genetics. Chemical genetics aims to target gene products using small molecules rather than to target the genes themselves by mutating an organism s genetic material.

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