Host Engineering Goal:
Generation of biomes and consortia with desired functions and ecologies.
We make the distinction between biomes and multicellular organisms through the definition of a biome as containing organisms (including multicellular organisms) with different genomes.
While a few microbiome systems are well characterized, such as rhizobium for nitrogen fixation, we are still struggling to understand and how and why consortia of microbes cooperate in nature. Systems with mutual metabolic dependencies (synthetic heterotrophs) have enabled the construction of engineered consortia that are stable in laboratory settings. Our ability to produce synthetic interactions is possible with some ongoing efforts; for example, a small number of synthetic microbial consortia have been created as model systems, consisting of 2-3 different organisms. Bioremediation and waste-water treatment demonstrate the principles that consortia can be used industrially, while probiotics and fecal microbe transplants demonstrate the principle that the composition of gut flora can be manipulated. Industrial startups in this space are emerging at a rapid pace, but our ability to make targeted changes, such as adding or removing a single organism, in an existing microbiome are very limited. Overall, our ability to understand and manipulate systems with specific functions or to remediate biomes and consortia that cease to function as desired is very limited.
Breakthrough Capabilities & Milestones
Ability to control cell-to-cell communication between different species.
Tightly-controlled promoter-response regulator systems that enable intra- and inter-species cellular communication.
Synthetic cell-to-cell communication elements and networks that function in a broad range of host organisms.
Signal-response pathways that function in synthetic communities of 5-10 organisms, employing a variety of pathway types and host species.
Ability to produce engineered microorganisms that can reliably invade and coexist within a complex community and manipulate the consortium/biome function and behavior.
Ability to characterize, manipulate, and program the three-dimensional (3D) architecture of a biome (i.e., the “ecosystem” of a natural or manipulated biome containing multiple species).
Use of existing technologies (including metagenomics, transcriptomics, proteomics, and mass spectrometry) to better understand the species composition and collective components of microbial communities and consortia.
Non-destructive, 3D visualization of microbial communities from a broad range of environments.
Ability to manipulate the 3D architecture of natural or engineered communities using external inputs (such as molecules, temperature, or pH).
Programmed communities that self-assemble into a desired 3D architecture.
Ability to control and/or define the function of an engineered microbial community/biome.
Ability to combine species with specialized functions to enable the production of desired products.
Assembly of consortia to produce desired molecules/products, considering community-level metabolic flux.
Plug-and-play assembly of consortia to produce desired molecules/products from specific starting materials, considering community level metabolic flux and organism-to-organism communication.
On-demand assembly of consortia that are programmed to respond dynamically, such that they can use different feedstocks, metabolize toxins or toxic byproducts, or produce different products in response to endogenous (system) or exogenous (user) cues.
Targeted modification of an existing microbiome to enable new functions or address dysbiosis – at the host, community, or environment level – through the addition, removal, or reorganization of the community members.
Use of existing technologies (including metagenomics, transcriptomics, proteomics, and mass spectrometry) to characterize functions of microbial communities from a broad range of environments.
Characterize how select microbiomes respond to changes in the environment, including the addition of toxins, the introduction new organisms (pathogens or commensals), and the selective removal of species from the community.
Predictive models of microbiome function and response to a broad range of environmental and ecological changes.
Ability to modify an existing biome or consortia as desired.
- Pacheco, A. R., Moel, M., & Segrè, D. (2019). Costless metabolic secretions as drivers of interspecies interactions in microbial ecosystems. Nature Communications, 10(1), 103. View publication.
- McCarty, N. S., & Ledesma-Amaro, R. (2019). Synthetic biology tools to engineer microbial communities for biotechnology. Trends in Biotechnology, 37(2), 181–197. View publication.; Kong, W., Meldgin, D. R., Collins, J. J., & Lu, T. (2018). Designing microbial consortia with defined social interactions. Nature Chemical Biology, 14(8), 821–829. View publication.
Last updated: June 19, 2019