Source 1primary paper2019ACS Synthetic Biology
Toolkit/cLIPS2
cLIPS2
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
cLIPS2 is a light-responsive multi-component switch identified from small libraries of cLIPS1 variants in a higher-throughput yeast screen. It binds human eIF4E in a light-dependent manner in vitro and inhibits translation in vivo in yeast harboring human eIF4E, with improved optical control relative to screened cLIPS1 variants.
Usefulness & Problems
Why this is useful
cLIPS2 is useful as an optogenetic regulator of eukaryotic translation initiation because it enables light-dependent engagement of human eIF4E and corresponding inhibition of translation in yeast. The reported improved degree of optical control suggests value for experiments requiring tighter light responsiveness than the screened cLIPS1 variants provided.
Source:
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
Source:
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Problem solved
cLIPS2 helps address the problem of achieving externally controllable inhibition of translation initiation through human eIF4E. The source specifically positions it as a product of a yeast discovery system for optogenetic inhibitors of eukaryotic translation initiation and a higher-throughput screen for improved optical control.
Problem links
Need better screening or enrichment leverage
DerivedcLIPS2 is a light-responsive multi-component switch derived from cLIPS1 variants that binds human eIF4E in a light-dependent manner and inhibits translation in yeast harboring human eIF4E. It was identified in a higher-throughput screen as a construct with improved optical control relative to screened cLIPS1 variants.
Need conditional recombination or state switching
DerivedcLIPS2 is a light-responsive multi-component switch derived from cLIPS1 variants that binds human eIF4E in a light-dependent manner and inhibits translation in yeast harboring human eIF4E. It was identified in a higher-throughput screen as a construct with improved optical control relative to screened cLIPS1 variants.
Need precise spatiotemporal control with light input
DerivedcLIPS2 is a light-responsive multi-component switch derived from cLIPS1 variants that binds human eIF4E in a light-dependent manner and inhibits translation in yeast harboring human eIF4E. It was identified in a higher-throughput screen as a construct with improved optical control relative to screened cLIPS1 variants.
Need tighter control over protein production
DerivedcLIPS2 is a light-responsive multi-component switch derived from cLIPS1 variants that binds human eIF4E in a light-dependent manner and inhibits translation in yeast harboring human eIF4E. It was identified in a higher-throughput screen as a construct with improved optical control relative to screened cLIPS1 variants.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
light-dependent binding to human eif4elight-dependent binding to human eif4elight-dependent control of translation initiationlight-dependent translation controlTranslation Controltranslation inhibitionTarget processes
recombinationselectiontranslationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedexplicitly named in anchor review: Trueimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementmethod family: local translation analysisoperating role: builderoperating role: regulatorswitch architecture: multi component
cLIPS2 was identified by adapting the yeast screen to higher throughput and testing small libraries of cLIPS1 variants. The available evidence indicates use in yeast harboring human eIF4E and dependence on light input, but it does not specify construct composition, cofactors, expression details, or delivery strategy.
The supplied evidence does not provide quantitative performance metrics, domain architecture, illumination wavelength, dynamic range, or kinetic parameters for cLIPS2. Validation is limited to in vitro binding and yeast-based in vivo translation inhibition, with no independent replication provided here.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
successYeastapplication demo
Inferred from claim c4 during normalization. cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo. Derived from claim c4. Quoted text: We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
Supporting Sources
Source 2review2022Trends in Neurosciences
Ranked Claims
The review explicitly discusses ciPSI, gePSI, cLIPS2, TRAP, and RiboTag as relevant methods for interrogating local or cell-type-specific protein synthesis in memory-related contexts.
The review frames spatiotemporally resolved protein synthesis and translational control as a molecular framework for memory consolidation.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 is a photoactivated inhibitor of translation.
We identified cLIPS1 (circularly permuted LOV inhibitor of protein synthesis 1), a fusion of a segment of 4EBP2 and a circularly permuted version of the LOV2 domain from Avena sativa, as a photoactivated inhibitor of translation.
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
Approval Evidence
2 sources5 linked approval claimsfirst-pass slug clips2
The web research summary states that the anchor review explicitly identifies cLIPS2 as an enabling method for studying local translation with high spatiotemporal resolution.
Source:
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
Source:
method use case summarysupports
The review explicitly discusses ciPSI, gePSI, cLIPS2, TRAP, and RiboTag as relevant methods for interrogating local or cell-type-specific protein synthesis in memory-related contexts.
Source:
review scope summarysupports
The review frames spatiotemporally resolved protein synthesis and translational control as a molecular framework for memory consolidation.
Source:
binding activitysupports
cLIPS1 and cLIPS2 bind human eIF4E in vitro in a light-dependent manner.
and bind human eIF4E in vitro in a light-dependent manner.
Source:
in vivo activitysupports
cLIPS1 and cLIPS2 can inhibit translation in yeast harboring human eIF4E in vivo.
We show that these constructs can both inhibit translation in yeast harboring a human eIF4E in vivo
Source:
optimization outcomesupports
cLIPS2 has an improved degree of optical control relative to cLIPS1 variants screened.
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
Source:
Comparisons
Source-backed strengths
The tool has evidence for both light-dependent in vitro binding to human eIF4E and in vivo translation inhibition in yeast harboring human eIF4E. It was also singled out from screened cLIPS1 variant libraries as having an improved degree of optical control.
Source:
Adapting the screen for higher throughput, we tested small libraries of cLIPS1 variants and found cLIPS2, a construct with an improved degree of optical control.
Compared with CRISPR/Cas9 system
cLIPS2 and CRISPR/Cas9 system address a similar problem space because they share recombination, selection, translation.
Shared frame: same top-level item type; shared target processes: recombination, selection, translation; shared mechanisms: translation_control
Relative tradeoffs: appears more independently replicated; looks easier to implement in practice.
Compared with light-inducible split Cre recombinase
cLIPS2 and light-inducible split Cre recombinase address a similar problem space because they share recombination, selection, translation.
Shared frame: same top-level item type; shared target processes: recombination, selection, translation; shared mechanisms: translation_control; same primary input modality: light
Compared with pooled library approach
cLIPS2 and pooled library approach address a similar problem space because they share recombination, selection, translation.
Shared frame: shared target processes: recombination, selection, translation; shared mechanisms: translation_control; same primary input modality: light
Relative tradeoffs: looks easier to implement in practice.
Ranked Citations
- 1.
- 2.