Source 1primary paper2023
Toolkit/intrinsically-disordered regions
intrinsically-disordered regions
Also known as: IDRs
Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Intrinsically disordered regions (IDRs) are protein domains used in engineered synthetic condensates to drive constitutive oligomerization and cluster formation. In the cited modular membraneless organelle design, IDR-mediated assembly is separated from cargo recruitment by fused interaction domains, enabling tunable control of condensate composition and function.
Usefulness & Problems
Why this is useful
IDRs are useful as modular assembly elements for building synthetic membraneless organelles without coupling scaffold formation directly to client recruitment. The cited system uses this separation to regulate protein interactions and metabolic flux through compositional tunability.
Source:
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
Problem solved
This approach addresses the engineering problem of constructing condensates whose physical assembly and molecular composition can be tuned independently. The cited framework specifically decouples cluster formation from protein recruitment, allowing functional control over recruited components.
Source:
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
Published Workflows
Objective: Engineer light-inducible synthetic transcription factors with improved transcriptional activation despite limitations of existing light-inducible gene switches.
Why it works: The abstract states that adding intrinsically disordered regions causes synthetic transcription factors to form droplets at target promoters, and that these droplets increase gene expression.
promoter-proximal liquid-liquid phase separationdroplet formation at target promoters via intrinsically disordered region incorporationoptogenetic engineeringquantitative mathematical modelingtransfection-based testing
Stages
- 1.Engineering phase-separating transcription factor designs(library_design)
This stage creates transcription factor designs intended to overcome limited performance of existing light-inducible gene switches.
Selection: Incorporation of intrinsically disordered regions to achieve liquid-liquid phase separation in constitutive and optogenetic synthetic transcription factors.
- 2.Model-supported mechanistic characterization(functional_characterization)
This stage tests whether the engineered phase-separation mechanism occurs and whether it improves transcriptional output.
Selection: Demonstration that engineered transcription factor droplets form at target promoters and increase gene expression.
- 3.Cross-context validation in mammalian cells and mice(confirmatory_validation)
This stage confirms that the engineered transcription factor improvement is not restricted to a single mammalian cell context.
Selection: Observation of increased performance in multiple mammalian cell lines and in mice following in situ transfection.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Component: A low-level protein part used inside a larger architecture that realizes a mechanism.
Techniques
No technique tags yet.
Target processes
No target processes tagged yet.
Implementation Constraints
Implementation is based on domain fusion, with IDRs providing the assembly module and separate interaction domains defining recruited composition. The available evidence does not specify expression system, delivery modality, stoichiometric design rules, or any required cofactors.
The supplied evidence does not define which specific IDR sequences, host systems, or quantitative performance metrics were validated in the engineered platform. Evidence for liquid-liquid phase separation is presented at the level of IDR propensity and general role in membraneless organelles, but direct tool-specific benchmarking is not provided here.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Source 2review2021International Journal of Molecular Sciences
Ranked Claims
The engineered synthetic condensate system is used to regulate protein interactions and metabolic flux through compositional tunability.
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
The engineered synthetic condensate system is used to regulate protein interactions and metabolic flux through compositional tunability.
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
The engineered synthetic condensate system is used to regulate protein interactions and metabolic flux through compositional tunability.
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
The engineered synthetic condensate system is used to regulate protein interactions and metabolic flux through compositional tunability.
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
The engineered synthetic condensate system is used to regulate protein interactions and metabolic flux through compositional tunability.
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
The engineered synthetic condensate system is used to regulate protein interactions and metabolic flux through compositional tunability.
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
The engineered synthetic condensate system is used to regulate protein interactions and metabolic flux through compositional tunability.
Finally, the engineered system is utilized to regulate protein interactions and metabolic flux by harnessing the system’s compositional tunability.
The paper demonstrates a modular framework for synthetic condensates that decouples cluster formation from protein recruitment.
we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment
The paper demonstrates a modular framework for synthetic condensates that decouples cluster formation from protein recruitment.
we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment
The paper demonstrates a modular framework for synthetic condensates that decouples cluster formation from protein recruitment.
we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment
The paper demonstrates a modular framework for synthetic condensates that decouples cluster formation from protein recruitment.
we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment
The paper demonstrates a modular framework for synthetic condensates that decouples cluster formation from protein recruitment.
we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment
The paper demonstrates a modular framework for synthetic condensates that decouples cluster formation from protein recruitment.
we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment
The paper demonstrates a modular framework for synthetic condensates that decouples cluster formation from protein recruitment.
we demonstrate a modular framework for the formation of synthetic condensates designed to decouple cluster formation and protein recruitment
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
A binding equilibrium model quantitatively describes protein partitioning into the condensate and supports predictive control of recruitment based on component expression levels and interaction affinity.
The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment.
A binding equilibrium model quantitatively describes protein partitioning into the condensate and supports predictive control of recruitment based on component expression levels and interaction affinity.
The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment.
A binding equilibrium model quantitatively describes protein partitioning into the condensate and supports predictive control of recruitment based on component expression levels and interaction affinity.
The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment.
A binding equilibrium model quantitatively describes protein partitioning into the condensate and supports predictive control of recruitment based on component expression levels and interaction affinity.
The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment.
A binding equilibrium model quantitatively describes protein partitioning into the condensate and supports predictive control of recruitment based on component expression levels and interaction affinity.
The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment.
A binding equilibrium model quantitatively describes protein partitioning into the condensate and supports predictive control of recruitment based on component expression levels and interaction affinity.
The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment.
A binding equilibrium model quantitatively describes protein partitioning into the condensate and supports predictive control of recruitment based on component expression levels and interaction affinity.
The composition of the proteins driven to partition into the condensate can be quantitatively described using a binding equilibrium model, demonstrating predictive control of how component expression levels and interaction affinity determine the degree of protein recruitment.
Intrinsically disordered regions are emphasized as important in the liquid-liquid phase separation behavior of transcription regulators.
Intrinsically disordered regions are emphasized as important in the liquid-liquid phase separation behavior of transcription regulators.
Intrinsically disordered regions are emphasized as important in the liquid-liquid phase separation behavior of transcription regulators.
Intrinsically disordered regions are emphasized as important in the liquid-liquid phase separation behavior of transcription regulators.
Intrinsically disordered regions are emphasized as important in the liquid-liquid phase separation behavior of transcription regulators.
Intrinsically disordered regions are emphasized as important in the liquid-liquid phase separation behavior of transcription regulators.
Membraneless organelles are formed via liquid-liquid phase separation driven by weak multivalent interactions between particular biomacromolecules.
Membraneless organelles are formed via liquid-liquid phase separation driven by weak multivalent interactions between particular biomacromolecules.
Membraneless organelles are formed via liquid-liquid phase separation driven by weak multivalent interactions between particular biomacromolecules.
Membraneless organelles are formed via liquid-liquid phase separation driven by weak multivalent interactions between particular biomacromolecules.
Membraneless organelles are formed via liquid-liquid phase separation driven by weak multivalent interactions between particular biomacromolecules.
Membraneless organelles are formed via liquid-liquid phase separation driven by weak multivalent interactions between particular biomacromolecules.
Different classes of transcription regulators have a propensity to undergo liquid-liquid phase separation.
Different classes of transcription regulators have a propensity to undergo liquid-liquid phase separation.
Different classes of transcription regulators have a propensity to undergo liquid-liquid phase separation.
Different classes of transcription regulators have a propensity to undergo liquid-liquid phase separation.
Different classes of transcription regulators have a propensity to undergo liquid-liquid phase separation.
Different classes of transcription regulators have a propensity to undergo liquid-liquid phase separation.
Approval Evidence
2 sources4 linked approval claimsfirst-pass slug intrinsically-disordered-regions
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs)
Source:
We gather crucial information regarding different classes of transcription regulators with the propensity to undergo liquid-liquid phase separation and stress the role of intrinsically disordered regions in this phenomenon.
Source:
mechanismsupports
Synthetic condensates are built through constitutive oligomerization of intrinsically disordered regions, while composition is independently defined through fused interaction domains.
Synthetic condensates are built through constitutive oligomerization of intrinsically-disordered regions (IDRs), which drive the formation of condensates whose composition can be independently defined through fused interaction domains.
Source:
mechanistic summarysupports
Intrinsically disordered regions are emphasized as important in the liquid-liquid phase separation behavior of transcription regulators.
Source:
mechanistic summarysupports
Membraneless organelles are formed via liquid-liquid phase separation driven by weak multivalent interactions between particular biomacromolecules.
Source:
property summarysupports
Different classes of transcription regulators have a propensity to undergo liquid-liquid phase separation.
Source:
Comparisons
Source-backed strengths
The main demonstrated strength is modularity: synthetic condensates are assembled through IDR constitutive oligomerization while composition is independently specified through fused interaction domains. The associated application evidence indicates that this design supports control of protein interactions and metabolic flux.
Ranked Citations
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