Representation of a Genetic Regulatory Circuit

Genetic regulatory circuits (also referred to as transcriptional regulatory circuits) is a concept that evolved from the

Operon In genetics, an operon is a functioning unit of DNA containing a cluster of genes under the control of a single promoter. The genes are transcribed together into an mRNA strand and either translated together in the cytoplasm, or undergo splic ...

Model discovered by

François Jacob François Jacob (; 17 June 1920 – 19 April 2013) was a French biologist who, together with Jacques Monod, originated the idea that control of enzyme levels in all cells occurs through regulation of transcription. He shared the 1965 Nobel ...

and

Jacques Monod Jacques Lucien Monod (; 9 February 1910 – 31 May 1976) was a French biochemist who won the Nobel Prize in Physiology or Medicine in 1965, sharing it with François Jacob and André Lwoff "for their discoveries concerning genetic control of e ...

. They are functional clusters of

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s that impact each other's expression through inducible

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

s and

cis-regulatory element ''Cis''-regulatory elements (CREs) or ''cis''-regulatory modules (CRMs) are regions of non-coding DNA which regulate the transcription of neighboring genes. CREs are vital components of genetic regulatory networks, which in turn control morpho ...

s. Genetic regulatory circuits are analogous in many ways to

electronic circuits An electronic circuit is composed of individual electronic components, such as resistors, transistors, capacitors, inductors and diodes, connected by conductive wires or traces through which electric current can flow. It is a type of electric ...

in how they use signal inputs and outputs to determine

gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...

. Like electronic circuits, their organization determines their efficiency, and this has been demonstrated in circuits working in series to have a greater sensitivity of gene regulation. They also use inputs such as trans and cis sequence regulators of genes, and outputs such as

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

level. Depending on the type of circuit, they respond constantly to outside signals, such as sugars and hormone levels, that determine how the circuit will return to its fixed point or periodic equilibrium state. Genetic regulatory circuits also have an ability to be evolutionarily rewired without the loss of the original transcriptional output level. This rewiring is defined by the change in regulatory-target gene interactions, while there is still conservation of regulatory factors and target genes.

In-silico application

These circuits can be modelled

in silico In biology and other experimental sciences, an ''in silico'' experiment is one performed on a computer or via computer simulation software. The phrase is pseudo-Latin for 'in silicon' (correct ), referring to silicon in computer chips. It was c ...

to predict the dynamics of a genetic system. Having constructed a

computational model A computational model uses computer programs to simulate and study complex systems using an algorithmic or mechanistic approach and is widely used in a diverse range of fields spanning from physics, engineering, chemistry and biology to economics ...

of the natural circuit of interest, one can use the model to make testable predictions about circuit performance. When designing a synthetic circuit for a specific engineering task, a model is useful for identifying necessary connections and parameter operating regimes that give rise to a desired functional output. Similarly, when studying a natural circuit, one can use the model to identify the parts or parameter values necessary for a desired biological outcome. In other words, computational modelling and experimental synthetic perturbations can be used to probe biological circuits. However, the structure of the circuits have shown to not be a reliable indicator of the function that the regulatory circuit provides for the larger cellular regulatory network.

Engineering and synthetic biology

Understanding of genetic regulatory circuits are key in the field of

synthetic biology Synthetic biology (SynBio) is a multidisciplinary field of science that focuses on living systems and organisms. It applies engineering principles to develop new biological parts, devices, and systems or to redesign existing systems found in nat ...

, where disparate genetic elements are combined to produce novel

biological function In evolutionary biology, function is the reason some object or process occurred in a system that evolved through natural selection. That reason is typically that it achieves some result, such as that chlorophyll helps to capture the energy of sunl ...

s. These biological gene circuits can be used synthetically to act as physical models for studying regulatory function. By engineering genetic regulatory circuits, cells can be modified to take information from their environment, such as nutrient availability and developmental signals, and react in accordance to changes in their surroundings . In plant synthetic biology, genetic regulatory circuits can be used to program traits to increase crop plant efficiency by increasing their robustness to environmental stressors. Additionally, they are used to produce

biopharmaceutical A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, t ...

s for medical intervention.

References

{{Reflist Genetics Gene expression Systems biology