Synthetic biology may be viewed as an effort to establish, formalize, and develop an engineering discipline in the context of biological systems. The ability to tune the properties of individual components is central to the process of system design in all fields of engineering, and synthetic biology is no exception. A large and growing number of approaches have been developed for tuning the responses of cellular systems, and here we address specifically the issue of tuning the rate of response of a system: given a system where an input affects the rate of change of an output, how can the shape of the response curve be altered experimentally? This affects a system’s dynamics as well as its steady-state properties, both of which are critical in the design of systems in synthetic biology, particularly those with multiple components. We begin by reviewing a mathematical formulation that captures a broad class of biological response curves and use this to define a standard set of varieties of tuning: vertical shifting, horizontal scaling, and the like. We then survey the experimental literature, classifying the results into our defined categories, and organizing them by regulatory level: transcriptional, post-transcriptional, and post-translational.
Malaria, a disease caused by the Plasmodium parasite carried by Anopheles mosquitoes, is commonly diagnosed by microscopy of peripheral blood smears and with rapid diagnostic tests. Both methods show limited detection of low parasitemia that may maintain transmission and hinder malaria elimination. We have developed a novel agglutination assay in which modified Saccharomyces cerevisiae cells act as antigendisplaying bead-like particles to capture malaria antibodies. The Epidermal Growth Factor-1 like domain (EGF1) of the Plasmodium falciparum merozoite surface protein-1 (PfMSP-1 19 ) was displayed on the yeast surface and shown to be capable of binding antimalaria antibodies. Mixed with a second yeast strain displaying the Z domain of Protein A from Staphylococcus aureus and allowed to settle in a round-bottomed well, the yeast produce a visually distinctive agglutination test result: a tight "button" at a low level of malarial antibodies, and a diffuse "sheet" when higher antibody levels are present. Positive agglutination results were observed in malaria-positive human serum to a serum dilution of 1:100 to 1:125. Since the yeast cells are inexpensive to produce, the test may be amenable to local production in regions seeking malaria surveillance information to guide their elimination programs.
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