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An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells.

ABSTRACT: Synthetic biology has the potential to bring forth advanced genetic devices for applications in healthcare and biotechnology. However, accurately predicting the behavior of engineered genetic devices remains difficult due to lack of modularity, wherein a device's output does not depend only on its intended inputs but also on its context. One contributor to lack of modularity is loading of transcriptional and translational resources, which can induce coupling among otherwise independently-regulated genes. Here, we quantify the effects of resource loading in engineered mammalian genetic systems and develop an endoribonuclease-based feedforward controller that can adapt the expression level of a gene of interest to significant resource loading in mammalian cells. Near-perfect adaptation to resource loads is facilitated by high production and catalytic rates of the endoribonuclease. Our design is portable across cell lines and enables predictable tuning of controller function. Ultimately, our controller is a general-purpose device for predictable, robust, and context-independent control of gene expression.

SUBMITTER: Jones RD

PROVIDER: S-EPMC7656454 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells.

Jones Ross D RD Qian Yili Y Siciliano Velia V DiAndreth Breanna B Huh Jin J Weiss Ron R Del Vecchio Domitilla D

Nature communications 20201110 1

Synthetic biology has the potential to bring forth advanced genetic devices for applications in healthcare and biotechnology. However, accurately predicting the behavior of engineered genetic devices remains difficult due to lack of modularity, wherein a device's output does not depend only on its intended inputs but also on its context. One contributor to lack of modularity is loading of transcriptional and translational resources, which can induce coupling among otherwise independently-regulat ...[more]

PMID: 33173034

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Project description:BackgroundAlthough laparoscopic surgery has made remarkable progress and become the standard approach for various surgical procedures worldwide over the past 30 years, its establishment in low-resource settings, particularly in public hospitals, has been challenging. The lack of equipment and trained expertise has hindered its widespread adoption in these settings. Cholecystectomy is one of the most commonly performed procedures using laparoscopy world wide AIM: The aim of the study is to determine whether laparoscopic cholecystectomy is feasible in a resource challenged setting METHODS: The research focused on individuals who underwent laparoscopic or open cholecystectomies at Yekatit 12 Hospital in Addis Ababa, Ethiopia, over a one-year period. Comprehensive data collection was conducted prospectively, encompassing both intraoperative and postoperative parameters. Follow-up was carried out via phone calls. The surgical procedures employed innovative techniques, including the reuse of sterilized single-use equipment and the utilization of local resources. The evaluation involved a comparison of demographic information, intraoperative details (such as critical view determination and operative duration), and postoperative complications, including assessments of pain and wound infections RESULTS: From August 2021 to September 2022, 119 patients were assessed. Among these patients, 65 (54.6%) underwent open cholecystectomies, while the remaining 54 (45.4%) underwent laparoscopic cholecystectomies. The average duration of the laparoscopic cholecystectomies was 90.7 min, which is 17.7 min behind the open. Patients in the laparoscopy group had significantly shorter hospital stays than the open group, and 94% were discharged by post operative day 2. The conversion rate from laparoscopic to open surgery was determined to be 3.3% CONCLUSION: To sum up, the safe execution of laparoscopic cholecystectomies is feasible in public hospitals and settings with limited resources, given adequate training and resource distribution. The study findings showcased superior outcomes, including reduced hospitalization duration and fewer complications, while maintaining comparable levels of operative duration and patient satisfaction in both groups.

Dataset Information

An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells.

Publications

An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells.

Similar Datasets

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