Biology subjects

Shaunak Sen

Publications and source records attributed to Shaunak Sen.

3 recordsLinked to original sources

bioRxiv2015

Design of a Toolbox of RNA Thermometers

Biomolecular temperature sensors can be used for efficient control of large-volume bioreactors, for spatiotemporal control and imaging of gene expression, as well as to engineer robustness to temperature in biomolecular circuit design. While RNA-based sensors, called thermometers, have been investigated in natural and synthetic contexts, an important challenge is to design different responses to temperature, differing in sensitivities and thresholds. We address this issue using experimental measurements in cells and in cell-free biomolecular breadboards in combination with computations of RNA thermodynamics. We designed a library of RNA thermometers, finding, computationally, that it could contain a multiplicity of responses to temperature. We constructed this library and found a wide range of responses to temperature, ranging from 3.5-fold to over 10-fold in the temperature range 29{degrees}C - 37{degrees}C. These were largely linear responses with over 10-fold difference in slopes. We correlated the measured responses with computational expectations, finding that while there was no strong correlation in the individual values, the overall trends were similar. These results present a toolbox of RNA-based circuit elements with varying temperature sensitivities.

Synthetic Biology↗

bioRxiv2014

Negative Feedback Facilitates Temperature Robustness in Biomolecular Circuit Dynamics

Temporal dynamics in many biomolecular circuits can change with temperature because of the temperature dependence of underlying reaction rate parameters. It is generally unclear what circuit mechanisms can inherently facilitate robustness in the dynamics to variations in temperature. Here, we address this issue using a combination of mathematical models and experimental measurements in a cell-free transcription-translation system. We find that negative transcriptional feedback can reduce the effect of temperature variation on circuit dynamics. Further, we find that effective negative feedback due to first-order degradation mechanisms can also enable such a temperature robustness effect. Finally, we estimate temperature dependence of key parameters mediating such negative feedback mechanisms. These results should be useful in the design of temperature robust circuit dynamics.

Systems Biology↗

bioRxiv2013

Designing Robustness to Temperature in a Feedforward Loop Circuit

Incoherent feedforward loops represent important biomolecular circuit elements capable of a rich set of dynamic behavior including adaptation and pulsed responses. Temperature can modulate some of these properties through its effect on the underlying reaction rate parameters. It is generally unclear how to design such a circuit where the properties are robust to variations in temperature. Here, we address this issue using a combination of tools from control and dynamical systems theory as well as preliminary experimental measurements towards such a design. We formalize temperature as an uncertainty acting on system dynamics, exploring both structured and unstructured uncertainty representations. Next, we analyze a standard incoherent feedforward loop circuit, noting mechanisms that intrinsically confer temperature robustness to some of its properties. Further, we explore different negative feedback configurations that can enhance the robustness to temperature. Finally, we find that the response of an incoherent feedforward loop circuit in cells can change with temperature. These results present groundwork for the design of a temperature-robust incoherent feedforward loop circuit.

Synthetic Biology↗