Ratios: Better than Absolutes

Why did we go to the trouble of developing sensors to detect ratios when so many already exist to detect absolute concentrations? Because ratios are better.

For many biological processes, absolute concentrations vary with time or environmental conditions. A sensor detecting the absolute concentration of a biologically significant molecule would respond to these fluctuations, creating systemic noise and false results. Our sensors can detect a "normalized" version of the molecule's concentration by comparing it to a different molecule whose regular cycles are similar.

Our unified sensor is also better than simply combining two absolute sensors into a single cell and comparing the outputs. Besides requiring the cell to produce fewer proteins (freeing up cell energy for other processes), our approach significantly reduces output noise. Additionally, a two-output system requires a human observer to take readings and make a decision. Our system can be hooked up straight to an output protein, allowing a rapid in-vivo response.

Applications

Ratiometric sensors are multifaceted tools with applications across the field of synthetic biology. Because our systems are modular, they could be used to sense ratios of chemicals important to...

Cancer

Ratios of growth factor to receptors can indicate the malignancy of tumors and predict when they are likely to metastasize. Our sensor could be used as either a research tool to discover more important ratios or as a method of targeting in-vivo drug delivery to those cells with tumor-like expression patterns.

Preterm Labor

Preterm labor is a leading cause of infant mortality, even in the US. Our sensor could detect hormone or bacterial imbalance and alert the expectant mother or her doctor that she is likely to enter preterm labor, allowing a pre-emptive response that could save her child's life.

Metabolic Flux

Bacterial manufacturing has huge economic potential, but is often limited by the efficiency of biological pathways. Our sensor could be used to regulate enzyme production, inhibiting enzyme output in the absence of substrate and increasing output once substrate becomes abundant.