Fundamental Trade-Offs in the Robustness of Biological Systems with Feedback Regulation DOI Creative Commons
Nguyen Tran,

An Nguyen,

Tasfia Wasima Rahman

и другие.

ACS Synthetic Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Natural biological systems use feedback regulation to effectively respond and adapt their changing environment. Even though in engineered we understand how accurate can be depending on the electronic or mechanical parts that it is implemented with, largely lack a similar theoretical framework study systems. Specifically, not fully understood quantified robust implementation of actually is. In this paper, sensitivity variations biochemical parameters using five example circuits: positive autoregulation, negative double-positive feedback, positive-negative double-negative (the toggle switch). We find some these examples are subjected fundamental performance trade-offs, propose multi-objective optimization as properties. The impact work improve circuit design for synthetic biology our understanding biology.

Язык: Английский

Context-aware deconvolution of cell–cell communication with Tensor-cell2cell DOI Creative Commons
Erick Armingol, Hratch Baghdassarian, Cameron Martino

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июнь 27, 2022

Abstract Cell interactions determine phenotypes, and intercellular communication is shaped by cellular contexts such as disease state, organismal life stage, tissue microenvironment. Single-cell technologies measure the molecules mediating cell–cell communication, emerging computational tools can exploit these data to decipher communication. However, current methods either disregard context or rely on simple pairwise comparisons between samples, thus limiting ability complex across multiple time points, levels of severity, spatial contexts. Here we present Tensor-cell2cell, an unsupervised method using tensor decomposition, which deciphers context-driven simultaneously accounting for stages, states, locations cells. To do so, Tensor-cell2cell uncovers patterns associated with different phenotypic states determined unique combinations cell types ligand-receptor pairs. As such, robustly improves upon extends analytical capabilities existing tools. We show identify modules distinct processes (e.g., participating pairs) linked severities Coronavirus Disease 2019 Autism Spectrum Disorder. Thus, introduce effective easy-to-use strategy understanding diverse conditions.

Язык: Английский

Процитировано

71

The diversification of methods for studying cell–cell interactions and communication DOI
Erick Armingol, Hratch Baghdassarian, Nathan E. Lewis

и другие.

Nature Reviews Genetics, Год журнала: 2024, Номер 25(6), С. 381 - 400

Опубликована: Янв. 18, 2024

Язык: Английский

Процитировано

57

Context-dependent redesign of robust synthetic gene circuits DOI Creative Commons

Austin Stone,

Abdelrahaman Youssef,

Sadikshya Rijal

и другие.

Trends in biotechnology, Год журнала: 2024, Номер 42(7), С. 895 - 909

Опубликована: Фев. 5, 2024

Cells provide dynamic platforms for executing exogenous genetic programs in synthetic biology, resulting highly context-dependent circuit performance. Recent years have seen an increasing interest understanding the intricacies of circuit–host relationships, their influence on bioengineering workflow, and devising strategies to alleviate undesired effects. We overview how emerging interactions, such as growth feedback resource competition, impact both deterministic stochastic behaviors. also emphasize control mitigating these unwanted This review summarizes latest advances current state host-aware resource-aware design gene circuits.

Язык: Английский

Процитировано

20

Integrating bioelectronics with cell-based synthetic biology DOI
Jonathan Rivnay, Ritu Raman, Jacob T. Robinson

и другие.

Nature Reviews Bioengineering, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

Процитировано

5

Predictive genetic circuit design for phenotype reprogramming in plants DOI Creative Commons
Ci Kong, Yin Yang, Tiancong Qi

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 16, 2025

Plants, with intricate molecular networks for environmental adaptation, offer groundbreaking potential reprogramming predictive genetic circuits. However, realizing this goal is challenging due to the long cultivation cycle of plants, as well lack reproducible, quantitative methods and well-characterized parts. Here, we establish a rapid (~10 days), quantitative, framework in plants. A group orthogonal sensors, modular synthetic promoters, NOT gates are constructed quantitatively characterized. model developed predict designed circuits' behavior accurately. Our versatile robust framework, validated by constructing 21 two-input circuits high prediction accuracy (R2 = 0.81), enables multi-state phenotype control both Arabidopsis thaliana Nicotiana benthamiana response chemical inducers. study achieves predictable design application offering valuable tools engineering plant traits biotechnology agriculture. The gene plants has been lagging behind other organisms. authors report designing reprograming expression hypersensitive response.

Язык: Английский

Процитировано

3

Machine learning for synthetic gene circuit engineering DOI
Sebastian Palacios,

James J. Collins,

Domitilla Del Vecchio

и другие.

Current Opinion in Biotechnology, Год журнала: 2025, Номер 92, С. 103263 - 103263

Опубликована: Янв. 27, 2025

Язык: Английский

Процитировано

2

Contextual computation by competitive protein dimerization networks DOI Creative Commons
Jacob Parres-Gold, Matthew E. Levine, Benjamin Emert

и другие.

Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

2

Customizing cellular signal processing by synthetic multi-level regulatory circuits DOI Creative Commons
Yuanli Gao, Lei Wang, Baojun Wang

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Дек. 18, 2023

As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. Towards this mission, novel regulatory mechanisms and genetic with unprecedented complexity have been implemented over past decade. These mechanisms, such as transcription translation control, could integrated into hybrid termed "multi-level circuits". The multi-level circuit design will tremendously benefit current paradigm, from modifying basic dynamics facilitating real-world applications, unleashing our capabilities customize cellular address global challenges through biology.

Язык: Английский

Процитировано

32

Degradation bottlenecks and resource competition in transiently and stably engineered mammalian cells DOI Creative Commons
Jacopo Gabrielli, Roberto Di Blasi, Cleo Kontoravdi

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Abstract Degradation tags, otherwise known as degrons, are portable sequences that can be used to alter protein stability. Here, we report degron-tagged proteins compete for cellular degradation resources in engineered mammalian cells leading coupling of the rates independently expressed when constitutively targeted human degrons adopted. We show effect this competition dependent on context degrons. By considering different proteins, degron position and hosts, highlight how impact both strength resource changes, with identification orthogonal combinations. adopting inducible bacterial plant also controlled uncoupling synthetic construct from native machinery achieved. then build a genomically integrated capacity monitor tagged confirm between genomic transiently DNA constructs. This work expands characterisation including systems, providing framework optimisation heterologous expression systems advance applications fundamental applied biological research.

Язык: Английский

Процитировано

1

High-throughput functional characterization of combinations of transcriptional activators and repressors DOI Open Access
Adi Mukund, Josh Tycko, Sage J. Allen

и другие.

Cell Systems, Год журнала: 2023, Номер 14(9), С. 746 - 763.e5

Опубликована: Авг. 4, 2023

Язык: Английский

Процитировано

22