Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A light tunable differentiation system for the creation and control of consortia in yeast.

ABSTRACT: Artificial microbial consortia seek to leverage division-of-labour to optimize function and possess immense potential for bioproduction. Co-culturing approaches, the preferred mode of generating a consortium, remain limited in their ability to give rise to stable consortia having finely tuned compositions. Here, we present an artificial differentiation system in budding yeast capable of generating stable microbial consortia with custom functionalities from a single strain at user-defined composition in space and in time based on optogenetically-driven genetic rewiring. Owing to fast, reproducible, and light-tunable dynamics, our system enables dynamic control of consortia composition in continuous cultures for extended periods. We further demonstrate that our system can be extended in a straightforward manner to give rise to consortia with multiple subpopulations. Our artificial differentiation strategy establishes a novel paradigm for the creation of complex microbial consortia that are simple to implement, precisely controllable, and versatile to use.

SUBMITTER: Aditya C

PROVIDER: S-EPMC8492667 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A tunable population timer in multicellular consortia.

Project description:Processing time-dependent information requires cells to quantify the duration of past regulatory events and program the time span of future signals. At the single-cell level, timer mechanisms can be implemented with genetic circuits. However, such systems are difficult to implement in single cells due to saturation in molecular components and stochasticity in the limited intracellular space. In contrast, multicellular implementations outsource some of the components of information-processing circuits to the extracellular space, potentially escaping these constraints. Here, we develop a theoretical framework, based on trilinear coordinate representation, to study the collective behavior of populations composed of three cell types under stationary conditions. This framework reveals that distributing different processes (in our case the production, detection and degradation of a time-encoding signal) across distinct strains enables the implementation of a multicellular timer. Our analysis also shows that the circuit can be easily tunable by varying the cellular composition of the consortium.

| S-EPMC8059065 | biostudies-literature

Creation and control of high-dimensional multi-partite classically entangled light.

Project description:Vector beams, non-separable in spatial mode and polarisation, have emerged as enabling tools in many diverse applications, from communication to imaging. This applicability has been achieved by sophisticated laser designs controlling the spin and orbital angular momentum, but so far is restricted to only two-dimensional states. Here we demonstrate the first vectorially structured light created and fully controlled in eight dimensions, a new state-of-the-art. We externally modulate our beam to control, for the first time, the complete set of classical Greenberger-Horne-Zeilinger (GHZ) states in paraxial structured light beams, in analogy with high-dimensional multi-partite quantum entangled states, and introduce a new tomography method to verify their fidelity. Our complete theoretical framework reveals a rich parameter space for further extending the dimensionality and degrees of freedom, opening new pathways for vectorially structured light in the classical and quantum regimes.

| S-EPMC7940607 | biostudies-literature

Light-inducible system for tunable protein expression in Neurospora crassa.

Project description:Filamentous fungi are important model systems for understanding eukaryotic cellular processes, including the study of protein expression. A salient feature of fungi is the ability of the protein-processing machinery to perform all of the extensive posttranslational modifications needed in the complex world of eukaryotic organisms, making them great hosts for production of eukaryotic proteins. In the model organism Neurospora crassa, several regulatable promoters have been used for heterologous gene expression but all suffer from leaky expression absent stimuli or an inability to induce protein expression at levels greater than those seen in vivo. To increase and better control in vivo protein expression in Neurospora, we have harnessed the light-induced vvd promoter. vvd promoter-driven mRNA expression is dependent upon light, shows a graded response, and is rapidly shut off when returned to the dark. The vvd promoter is a highly tunable and regulatable system, which could be a useful instrument for those interested in efficient and controllable gene expression.

| S-EPMC3464113 | biostudies-literature

Light-mediated control of DNA transcription in yeast.

Project description:A variety of methods exist for inducible control of DNA transcription in yeast. These include the use of native yeast promoters or regulatory elements that are responsive to small molecules such as galactose, methionine, and copper, or engineered systems that allow regulation by orthogonal small molecules such as estrogen. While chemically regulated systems are easy to use and can yield high levels of protein expression, they often provide imprecise control over protein levels. Moreover, chemically regulated systems can affect many other proteins and pathways in yeast, activating signaling pathways or physiological responses. Here, we describe several methods for light mediated control of DNA transcription in vivo in yeast. We describe methodology for using a red light and phytochrome dependent system to induce transcription of genes under GAL1 promoter control, as well as blue light/cryptochrome dependent systems to control transcription of genes under GAL1 promoter or LexA operator control. Light is dose dependent, inexpensive to apply, easily delivered, and does not interfere with cellular pathways, and thus has significant advantages over chemical systems.

| S-EPMC3526682 | biostudies-literature

The REMOTE-control system: a system for reversible and tunable control of endogenous gene expression in mice.

Project description:We report here a robust, tunable, and reversible transcription control system for endogenous genes. The REMOTE-control system (Reversible Manipulation of Transcription at Endogenous loci) employs enhanced lac repression and tet activation systems. With this approach, we show in mouse embryonic stem cells that endogenous Dnmt1 gene transcription could be up- or downregulated in a tunable, inducible, and reversible manner across nearly two orders of magnitude. Transcriptional repression of Dnmt1 by REMOTE-control was potent enough to cause embryonic lethality in mice, reminiscent of a genetic knockout of Dnmt1 and could substantially suppress intestinal polyp formation when applied to an ApcMin model. Binding by the enhanced lac repressor was sufficiently tight to allow strong attenuation of transcriptional elongation, even at operators located many kilobases downstream of the transcription start site and to produce invariably tight repression of all of the strong viral/mammalian promoters tested. Our approach of targeting tet transcriptional activators to the endogenous Dnmt1 promoter resulted in robust upregulation of this highly expressed housekeeping gene. Our system provides exquisite control of the level, timing, and cell-type specificity of endogenous gene expression, and the potency and versatility of the system will enable high resolution in vivo functional analyses.

| S-EPMC5716148 | biostudies-literature

Computational implementation of a tunable multicellular memory circuit for engineered eukaryotic consortia.

Project description:Cells are complex machines capable of processing information by means of an entangled network of molecular interactions. A crucial component of these decision-making systems is the presence of memory and this is also a specially relevant target of engineered synthetic systems. A classic example of memory devices is a 1-bit memory element known as the flip-flop. Such system can be in principle designed using a single-cell implementation, but a direct mapping between standard circuit design and a living circuit can be cumbersome. Here we present a novel computational implementation of a 1-bit memory device using a reliable multicellular design able to behave as a set-reset flip-flop that could be implemented in yeast cells. The dynamics of the proposed synthetic circuit is investigated with a mathematical model using biologically-meaningful parameters. The circuit is shown to behave as a flip-flop in a wide range of parameter values. The repression strength for the NOT logics is shown to be crucial to obtain a good flip-flop signal. Our model also shows that the circuit can be externally tuned to achieve different memory states and dynamics, such as persistent and transient memory. We have characterized the parameter domains for robust memory storage and retrieval as well as the corresponding time response dynamics.

| S-EPMC4598587 | biostudies-literature

Single strain control of microbial consortia.

Project description:The scope of bioengineering is expanding from the creation of single strains to the design of microbial communities, allowing for division-of-labour, specialised sub-populations and interaction with "wild" microbiomes. However, in the absence of stabilising interactions, competition between microbes inevitably leads to the removal of less fit community members over time. Here, we leverage amensalism and competitive exclusion to stabilise a two-strain community by engineering a strain of Escherichia coli which secretes a toxin in response to competition. We show experimentally and mathematically that such a system can produce stable populations with a composition that is tunable by easily controllable parameters. This system creates a tunable, stable two-strain consortia while only requiring the engineering of a single strain.

| S-EPMC8010080 | biostudies-literature

Ubiquitination-dependent control of sexual differentiation in fission yeast.

Project description:In fission yeast, meiosis-specific transcripts are selectively eliminated during vegetative growth by the combined action of the YTH-family RNA-binding protein Mmi1 and the nuclear exosome. Upon nutritional starvation, the master regulator of meiosis Mei2 inactivates Mmi1, thereby allowing expression of the meiotic program. Here, we show that the E3 ubiquitin ligase subunit Not4/Mot2 of the evolutionarily conserved Ccr4-Not complex, which associates with Mmi1, promotes suppression of meiotic transcripts expression in mitotic cells. Our analyses suggest that Mot2 directs ubiquitination of Mei2 to preserve the activity of Mmi1 during vegetative growth. Importantly, Mot2 is not involved in the constitutive pathway of Mei2 turnover, but rather plays a regulatory role to limit its accumulation or inhibit its function. We propose that Mmi1 recruits the Ccr4-Not complex to counteract its own inhibitor Mei2, thereby locking the system in a stable state that ensures the repression of the meiotic program by Mmi1.

| S-EPMC5614563 | biostudies-literature

A switchable light-input, light-output system modelled and constructed in yeast.

Project description:Advances in synthetic biology will require spatio-temporal regulation of biological processes in heterologous host cells. We develop a light-switchable, two-hybrid interaction in yeast, based upon the Arabidopsis proteins PHYTOCHROME A and FAR-RED ELONGATED HYPOCOTYL 1-LIKE. Light input to this regulatory module allows dynamic control of a light-emitting LUCIFERASE reporter gene, which we detect by real-time imaging of yeast colonies on solid media.The reversible activation of the phytochrome by red light, and its inactivation by far-red light, is retained. We use this quantitative readout to construct a mathematical model that matches the system's behaviour and predicts the molecular targets for future manipulation.Our model, methods and materials together constitute a novel system for a eukaryotic host with the potential to convert a dynamic pattern of light input into a predictable gene expression response. This system could be applied for the regulation of genetic networks - both known and synthetic.

| S-EPMC2758823 | biostudies-other

A System for Gene Expression Noise Control in Yeast.

Project description:Gene expression noise arises from stochastic variation in the synthesis and degradation of mRNA and protein molecules and creates differences in protein numbers across populations of genetically identical cells. Such variability can lead to imprecision and reduced performance of both native and synthetic networks. In principle, gene expression noise can be controlled through the rates of transcription, translation and degradation, such that different combinations of those rates lead to the same protein concentrations but at different noise levels. Here, we present a "noise tuner" which allows orthogonal control over the transcription and the mRNA degradation rates by two different inducer molecules. Combining experiments with theoretical analysis, we show that in this system the noise is largely determined by the transcription rate, whereas the mean expression is determined by both the transcription rate and mRNA stability and can thus be decoupled from the noise. This noise tuner enables 2-fold changes in gene expression noise over a 5-fold range of mean protein levels. We demonstrated the efficacy of the noise tuner in a complex regulatory network by varying gene expression noise in the mating pathway of Saccharomyces cerevisiae, which allowed us to control the output noise and the mutual information transduced through the pathway. The noise tuner thus represents an effective tool of gene expression noise control, both to interrogate noise sensitivity of natural networks and enhance performance of synthetic circuits.

| S-EPMC6243393 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data