nathaliaraquelx
commented
3 years ago Overall, I found this study mind-blowing, I think it would be feasible to design an approach to target a specific problem utilizing this microbial consortia prediction system. And maybe even characterize it in different organisms as they’ve done here.
Tools for engineering coordinated system behavior in synthetic microbial consortia
DOI: 10.1038/s41467-018-05046-2
- Introduction:
They start by reviewing a few of the most studied synthetic biology applications and then try to put it in a current context:
“De novo implementation of genetic circuits of increasing complexity and size in living cells is an important challenge in synthetic biology”.
Then, they call for attention on the following problems:
“Obstacles include unwanted interactions between genetic parts, restrictions on the number of available genetic parts, limits to the size of DNA that can be transformed into the host cell and metabolic burden to the host chassis”.
- Methodology:
The engineering of microbial consortia is presented as a potential solution, since:
“[...] the use of synthetic consortia could enable compartmentalisation, cell specialisation, parallel biocomputation, increased bioprocess efficiency and spatial organisation”.
And the most simple genetic architecture to engineer cell-to-cell communication is by quorum sensing systems (e.g. acyl-homoserine lactones).
The aim of this study is to create the largest characterised library of quorum-sensing devices with mapped chemical crosstalk interactions.
How cool is that?!
"The fact that this database contains data about all possible combinations of AHL-receiver devices and AHL inducers enables us to create a software tool to automatically select orthogonal AHL communication channels. This automated process facilitates the design of synthetic microbial consortia".
- Conclusion:
It is expected that the ability to rationally design synthetic consortia of microorganisms can provide elegant and efficient solutions for bioenergy production from renewable resources as is the case for prototroph/heterotroph cell factories.
"Other foreseeable applications of cell consortia will probably take advantage of the parallel biocomputation enabled by molecular compartmentalisation to interrogate multiple biomarkers simultaneously. First applications may apply to areas such as microbiome engineering and next-generation medical diagnostics, and then interface with human physiology to effect change during pathology via integrated genetic logic. Finally, the current efforts in engineering microbial consortia will provide a better understanding of multicellular systems behaviour and will develop foundational technologies for future applications in tissue and/or organ engineering that will transform cell-based therapeutic interventions”.
This study made me think about the possibility to study cell-cell communication in microbiota (maybe gut microbiota, microbiota from dairy products, or even rhizosphere). It could be really interesting.
A synthetic mammalian network to compute population borders based on engineered reciprocal cell-cell communication
They highlight the importance of communication between specialized cells and the utilization of synthetic biology as means to study communication between cell populations and also towards deeper understanding of artificial tissue engineering.
Here they give a description of the problem involving population borders (which their study aims to investigate):
“One particular example of inter cellular communication is the exchange of information between adjacent cell populations in order to define and detect population borders. The importance of this mechanism is probably best illustrated in cancer cells that lose the ability to detect and react to such borders during unregulated tumor growth and metastasis”.
Disclaimer on these border cells:
Their design is based on two distinct populations of cells that communicate via defined signaling molecules.
This process, then, happens in a dose-dependent manner.
L-tryptophan diffuses across the population border into the processing cell population, where it is perceived by a fusion protein of the DNA-binding domain of the tryptophan repressor (TrpR).
Upon binding of L-tryptophan,the TrpR domain binds to its cognate operator sequence in a response construct and the production of the second signaling molecule, interleukin-4, is initiated.
Interleukin-4 diffuses back across the population border and is perceived by the sender/receiver cell population via the interleukin-4 receptor and the signal activates the expression of gene encoding the fluorescent reporter protein YFP.
Finally, the width of the edge between the cell populations as visualized by expression of the YFP reporter can be directly correlated to the sensitivity of the sender/receiver population towards interleukin-4 and to the production of interleukin-4 by the processing cell line.