Cellular Biosensors with Engineered Genetic Circuits (Saltepe, Behide, et al. 2018)

[KaroGu]

Article: Saltepe, Behide, et al. “Cellular Biosensors with Engineered Genetic Circuits.” ACS Sensors, vol. 3, no. 1, Jan. 2018, pp. 13–26. DOI.org (Crossref), doi:10.1021/acssensors.7b00728.

A review that focuses on biocomputational tools and their applications in biosensor studies, identifies some drawbacks and regulations of whole cell sensors in terms of biomedical and environmental safety concerns.

As a general design strategy there are three different approaches:

1. Designing a reporter circuit based on the cellular system
2. Designing a system to obtain whole cell as effectors
3. Wiring multiple cells via synthetic circuits

Optical output signals are the most preferred. Other types of output signals can be listed: changes in metabolic activity, gene expression profile, pH as a response of inducer agent. Multiplexing simultaneous usage of different reporter proteins allows multiple output detection of biosensors.

Cellular sensors for Biomedical Applications

• For infectious disease: non – invasive, rapid and accurate diagnosis of infections is of considerable importance for optimization of treatment and survival of patients
• For cancer: some teams made E.coli that predicted patients ability to respond to leukemia drugs before starting the treatment
• Detection of metabolic disorders: based on biomarkers such as metabolites or proteins. Detection is limited by the low concentration of biomarkers in a complex biological environment

Environment and biosensors

• Cellular sensors for environmental monitoring: detecting heavy metals, hazardous organic toxic materials to the environment.
• Low biodegradability, heavy metals accumulate in living organisms and the environment which in turn can result in ecological toxicity or human disease.
• To analyze environmental samples in conventional environmental monitoring, analytical instrumentation as well as expertise are needed -> the process is expensive, time – consuming and relatively slow. Does not give information about bioavailability or effects on organisms.
• Using biosensors could aid in environmental monitoring studies to control bioavailability, toxicity, genotoxicity of pollutants on living systems.
• Many biosensors focus on figuring out the toxicity of the sample rather than detecting what the sample is.
• Drawbacks of microbial sensors in analysis of heavy metals: underperformance in sensitivity and selectivity especially in multiplex detection, providing population level data which is directly affected by genotypical and therefore phenotypical heterogeneity of the population and stochastic protein expression.
• Possible solution: combination of micro/nano technologies and microbial biosensors.
• Some advantages include: cost effectiveness, time savings, suitability for high throughput analysis of multiple samples.

To keep in mind: GMOs, cannot release to the environment, risk governance is applied to the field.

Strategies to prevent the release to the environment:

• use plasmids as vectors to carry synthetic circuits rather than introducing to the genome.
• designing a vector which does not share high similarity between mobile elements of host genome
• developing microbial kill switches and other vector suicide strategies.
• as a novel strategy orthogonal biology or xenobiology is used.