Retroactivity attenuation through signal transduction cascades
This paper considers the problem of attenuating retroactivity, that is, the effect of loads in biological networks and demonstrates that signal transduction cascades incorporating phosphotransfer modules have remarkable retroactivity attenuation ability. Uncovering the biological mechanisms for retr...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Institute of Electrical and Electronics Engineers (IEEE)
2015
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| Online Access: | http://hdl.handle.net/1721.1/97417 https://orcid.org/0000-0001-6472-8576 |
| _version_ | 1811091373309296640 |
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| author | Rivera, Phillip M. Del Vecchio, Domitilla |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Rivera, Phillip M. Del Vecchio, Domitilla |
| author_sort | Rivera, Phillip M. |
| collection | MIT |
| description | This paper considers the problem of attenuating retroactivity, that is, the effect of loads in biological networks and demonstrates that signal transduction cascades incorporating phosphotransfer modules have remarkable retroactivity attenuation ability. Uncovering the biological mechanisms for retroactivity attenuation is relevant in synthetic biology to enable bottom-up modular composition of complex circuits. It is also important in systems biology for deepening our current understanding of natural principles of modular organization. In this paper, we perform a combined theoretical and computational study of a cascade system comprising two phosphotransfer modules, ubiquitous in eukaryotic signal transduction, when subject to load from downstream targets. Employing singular perturbation on the finite time interval, we demonstrate that this system implements retroactivity attenuation when the input signal is sufficiently slow. Employing trajectory sensitivity analysis about nominal parameters that we have identified from in vivo data, we further demonstrate that the key parameters for retroactivity attenuation are those controlling the timescale of the system. |
| first_indexed | 2024-09-23T15:01:23Z |
| format | Article |
| id | mit-1721.1/97417 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:01:23Z |
| publishDate | 2015 |
| publisher | Institute of Electrical and Electronics Engineers (IEEE) |
| record_format | dspace |
| spelling | mit-1721.1/974172022-09-29T12:06:06Z Retroactivity attenuation through signal transduction cascades Rivera, Phillip M. Del Vecchio, Domitilla Massachusetts Institute of Technology. Department of Mechanical Engineering Rivera, Phillip M. Del Vecchio, Domitilla This paper considers the problem of attenuating retroactivity, that is, the effect of loads in biological networks and demonstrates that signal transduction cascades incorporating phosphotransfer modules have remarkable retroactivity attenuation ability. Uncovering the biological mechanisms for retroactivity attenuation is relevant in synthetic biology to enable bottom-up modular composition of complex circuits. It is also important in systems biology for deepening our current understanding of natural principles of modular organization. In this paper, we perform a combined theoretical and computational study of a cascade system comprising two phosphotransfer modules, ubiquitous in eukaryotic signal transduction, when subject to load from downstream targets. Employing singular perturbation on the finite time interval, we demonstrate that this system implements retroactivity attenuation when the input signal is sufficiently slow. Employing trajectory sensitivity analysis about nominal parameters that we have identified from in vivo data, we further demonstrate that the key parameters for retroactivity attenuation are those controlling the timescale of the system. Grant FA9550-12-1-0219 National Science Foundation (U.S.). Division of Computing and Communication Foundations (1058127) 2015-06-15T16:10:34Z 2015-06-15T16:10:34Z 2014-06 Article http://purl.org/eprint/type/ConferencePaper 978-1-4799-3274-0 978-1-4799-3272-6 978-1-4799-3271-9 0743-1619 http://hdl.handle.net/1721.1/97417 Rivera, Phillip M., and Domitilla Del Vecchio. “Retroactivity Attenuation through Signal Transduction Cascades.” 2014 American Control Conference (June 2014). https://orcid.org/0000-0001-6472-8576 en_US http://dx.doi.org/10.1109/ACC.2014.6858840 Proceedings of the 2014 American Control Conference Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Institute of Electrical and Electronics Engineers (IEEE) MIT web domain |
| spellingShingle | Rivera, Phillip M. Del Vecchio, Domitilla Retroactivity attenuation through signal transduction cascades |
| title | Retroactivity attenuation through signal transduction cascades |
| title_full | Retroactivity attenuation through signal transduction cascades |
| title_fullStr | Retroactivity attenuation through signal transduction cascades |
| title_full_unstemmed | Retroactivity attenuation through signal transduction cascades |
| title_short | Retroactivity attenuation through signal transduction cascades |
| title_sort | retroactivity attenuation through signal transduction cascades |
| url | http://hdl.handle.net/1721.1/97417 https://orcid.org/0000-0001-6472-8576 |
| work_keys_str_mv | AT riveraphillipm retroactivityattenuationthroughsignaltransductioncascades AT delvecchiodomitilla retroactivityattenuationthroughsignaltransductioncascades |