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Author Spotlight: A Streamlined Approach to Studying Cell Death Initiation in Hypersensitive Response
Published on: November 10, 2023
Selective induction of programmed cell death using synthetic biology tools
Kateryna Shkarina1, Petr Broz2
1Institute of Innate Immunity, University Hospital Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Abstract:
Regulated cell death (RCD) controls the removal of dispensable, infected or malignant cells, and is thus essential for development, homeostasis and immunity of multicellular organisms. Over the last years different forms of RCD have been described (among them apoptosis, necroptosis, pyroptosis and ferroptosis), and the cellular signaling pathways that control their induction and execution have been characterized at the molecular level. It has also become apparent that different forms of RCD differ in their capacity to elicit inflammation or an immune response, and that RCD pathways show a remarkable plasticity. Biochemical and genetic studies revealed that inhibition of a given pathway often results in the activation of back-up cell death mechanisms, highlighting close interconnectivity based on shared signaling components and the assembly of multivalent signaling platforms that can initiate different forms of RCD. Due to this interconnectivity and the pleiotropic effects of 'classical' cell death inducers, it is challenging to study RCD pathways in isolation. This has led to the development of tools based on synthetic biology that allow the targeted induction of RCD using chemogenetic or optogenetic methods. Here we discuss recent advances in the development of such toolset, highlighting their advantages and limitations, and their application for the study of RCD in cells and animals.
Insights
Regulated cell death (RCD) pathways are crucial for multicellular life. Synthetic biology tools now enable precise RCD induction, overcoming challenges in studying interconnected cell death mechanisms in cells and animals.
Area of Science:
- Cellular Biology
- Immunology
- Developmental Biology
Background:
- Regulated cell death (RCD) removes unwanted cells, vital for organism development, homeostasis, and immunity.
- Multiple RCD forms exist (apoptosis, necroptosis, pyroptosis, ferroptosis), with characterized signaling pathways.
- RCD pathways exhibit plasticity and interconnectivity, complicating isolated study.
Purpose of the Study:
- To review advances in synthetic biology tools for targeted RCD induction.
- To highlight the advantages and limitations of these novel RCD research tools.
- To discuss the application of these tools in studying RCD in biological systems.
Main Methods:
- Discussion of chemogenetic and optogenetic tools for RCD induction.
- Analysis of synthetic biology approaches for precise control of cell death.
- Review of existing literature on RCD pathway interconnectivity and plasticity.
Main Results:
- Synthetic biology tools offer targeted RCD induction, overcoming limitations of classical methods.
- These tools enable the study of RCD pathways in isolation and in complex biological contexts.
- Demonstrated advantages and limitations of chemogenetic and optogenetic RCD induction methods.
Conclusions:
- Synthetic biology tools are powerful for dissecting complex RCD signaling.
- Targeted RCD induction facilitates research into cell death mechanisms and immune responses.
- These advancements are crucial for understanding RCD in development, homeostasis, and disease.
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