Automatic design of gene regulatory mechanisms for spatial pattern formation
Abstract Gene regulatory mechanisms (GRMs) control the formation of spatial and temporal expression patterns that can serve as regulatory signals for the development of complex shapes. Synthetic developmental biology aims to engineer such genetic circuits for understanding and producing desired mult...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | npj Systems Biology and Applications |
| Online Access: | https://doi.org/10.1038/s41540-024-00361-5 |
| _version_ | 1797219748497326080 |
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| author | Reza Mousavi Daniel Lobo |
| author_facet | Reza Mousavi Daniel Lobo |
| author_sort | Reza Mousavi |
| collection | DOAJ |
| description | Abstract Gene regulatory mechanisms (GRMs) control the formation of spatial and temporal expression patterns that can serve as regulatory signals for the development of complex shapes. Synthetic developmental biology aims to engineer such genetic circuits for understanding and producing desired multicellular spatial patterns. However, designing synthetic GRMs for complex, multi-dimensional spatial patterns is a current challenge due to the nonlinear interactions and feedback loops in genetic circuits. Here we present a methodology to automatically design GRMs that can produce any given two-dimensional spatial pattern. The proposed approach uses two orthogonal morphogen gradients acting as positional information signals in a multicellular tissue area or culture, which constitutes a continuous field of engineered cells implementing the same designed GRM. To efficiently design both the circuit network and the interaction mechanisms—including the number of genes necessary for the formation of the target spatial pattern—we developed an automated algorithm based on high-performance evolutionary computation. The tolerance of the algorithm can be configured to design GRMs that are either simple to produce approximate patterns or complex to produce precise patterns. We demonstrate the approach by automatically designing GRMs that can produce a diverse set of synthetic spatial expression patterns by interpreting just two orthogonal morphogen gradients. The proposed framework offers a versatile approach to systematically design and discover complex genetic circuits producing spatial patterns. |
| first_indexed | 2024-04-24T12:38:35Z |
| format | Article |
| id | doaj.art-9cff918300394b25adfdbefacf40d5f5 |
| institution | Directory Open Access Journal |
| issn | 2056-7189 |
| language | English |
| last_indexed | 2024-04-24T12:38:35Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Systems Biology and Applications |
| spelling | doaj.art-9cff918300394b25adfdbefacf40d5f52024-04-07T11:22:29ZengNature Portfolionpj Systems Biology and Applications2056-71892024-04-0110111310.1038/s41540-024-00361-5Automatic design of gene regulatory mechanisms for spatial pattern formationReza Mousavi0Daniel Lobo1Department of Biological Sciences, University of Maryland, Baltimore CountyDepartment of Biological Sciences, University of Maryland, Baltimore CountyAbstract Gene regulatory mechanisms (GRMs) control the formation of spatial and temporal expression patterns that can serve as regulatory signals for the development of complex shapes. Synthetic developmental biology aims to engineer such genetic circuits for understanding and producing desired multicellular spatial patterns. However, designing synthetic GRMs for complex, multi-dimensional spatial patterns is a current challenge due to the nonlinear interactions and feedback loops in genetic circuits. Here we present a methodology to automatically design GRMs that can produce any given two-dimensional spatial pattern. The proposed approach uses two orthogonal morphogen gradients acting as positional information signals in a multicellular tissue area or culture, which constitutes a continuous field of engineered cells implementing the same designed GRM. To efficiently design both the circuit network and the interaction mechanisms—including the number of genes necessary for the formation of the target spatial pattern—we developed an automated algorithm based on high-performance evolutionary computation. The tolerance of the algorithm can be configured to design GRMs that are either simple to produce approximate patterns or complex to produce precise patterns. We demonstrate the approach by automatically designing GRMs that can produce a diverse set of synthetic spatial expression patterns by interpreting just two orthogonal morphogen gradients. The proposed framework offers a versatile approach to systematically design and discover complex genetic circuits producing spatial patterns.https://doi.org/10.1038/s41540-024-00361-5 |
| spellingShingle | Reza Mousavi Daniel Lobo Automatic design of gene regulatory mechanisms for spatial pattern formation npj Systems Biology and Applications |
| title | Automatic design of gene regulatory mechanisms for spatial pattern formation |
| title_full | Automatic design of gene regulatory mechanisms for spatial pattern formation |
| title_fullStr | Automatic design of gene regulatory mechanisms for spatial pattern formation |
| title_full_unstemmed | Automatic design of gene regulatory mechanisms for spatial pattern formation |
| title_short | Automatic design of gene regulatory mechanisms for spatial pattern formation |
| title_sort | automatic design of gene regulatory mechanisms for spatial pattern formation |
| url | https://doi.org/10.1038/s41540-024-00361-5 |
| work_keys_str_mv | AT rezamousavi automaticdesignofgeneregulatorymechanismsforspatialpatternformation AT daniellobo automaticdesignofgeneregulatorymechanismsforspatialpatternformation |