The computational capabilities of many-to-many protein interaction networks
Abstract
Many biological circuits comprise sets of protein variants that interact with one another in a many-to-many, or promiscuous, fashion. These architectures can provide powerful computational capabilities that are especially critical in multicellular organisms. Understanding the principles of biochemical computations in these circuits could allow more precise cellular control of cellular behaviors. However, these systems are inherently difficult to analyze, due to their large number of interacting molecular components, partial redundancies, and cell context dependence. Here, we discuss recent experimental and theoretical advances that are beginning to reveal how promiscuous circuits compute, what roles those computations play in natural biological contexts, and how promiscuous architectures can be applied for the design of synthetic multicellular behaviors.
Copyright and License
© 2023 Elsevier.
Acknowledgement
H.E.K. is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRG-2472-22). J.G.-O. is supported by project PID2021-127311NB-I00 financed by the Spanish Ministry of Science and Innovation, the Spanish State Research Agency and FEDER (MICIN/AEI/10.13039/501100011033/FEDER), by the Maria de Maeztu Programme for Units of Excellence in R&D (project CEX2018-000792-M), and by the Generalitat de Catalunya (ICREA Academia Programme). Work in the lab of M.B.E. was supported by the National Institutes of Health grants R01 HD075335A and R01 MH116508, by the Paul G. Allen Frontiers Group and Prime Awarding Agency under award no. UWSC10142, and by the National Science Foundation grant EF-2021552 under subaward UWSC10278. Y.E.A. is supported by the Israel Science Foundation (grant no. 1105/20) and is the incumbent Sygnet Career Development Chair for Bioinformatics.
Conflict of Interest
M.B.E. is a scientific advisory board member or consultant at TeraCyte, Primordium, and Spatial Genomics. Y.E.A. is a scientific advisory board member or consultant at TeraCyte.
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Additional details
- PMCID
- PMC10318606
- Damon Runyon Cancer Research Foundation
- DRG-2472-22
- Agencia Estatal de Investigación
- PID2021-127311NB-I00
- European Union
- European Regional Development Fund
- Ministerio de Ciencia, Innovación y Universidades
- Agencia Estatal de Investigación
- MICIN/AEI/10.13039 / 501100011033/FEDER
- Agencia Estatal de Investigación
- CEX2018-000792-M
- Generalitat de Catalunya
- National Institutes of Health
- R01 MH116508
- National Institutes of Health
- R01 HD075335A
- Paul G. Allen Family Foundation
- National Science Foundation
- UWSC10278
- National Science Foundation
- EF-2021552
- National Science Foundation
- UWSC10142
- Israel Science Foundation
- 1105/20
- Weizmann Institute of Science
- Sygnet Career Development Chair for Bioinformatics
- Caltech groups
- Division of Biology and Biological Engineering