Department of Bioengineering, Northeastern University, Boston, MA 02115, USA.
Department of Physics, Harvard University, Cambridge, MA 02138, USA.
Biomolecules. 2022 Nov 7;12(11):1645. doi: 10.3390/biom12111645.
The Heat Shock Response (HSR) is a highly conserved genetic system charged with protecting the proteome in a wide range of organisms and species. Experiments since the early 1980s have elucidated key elements in these pathways and revealed a canonical mode of regulation, which relies on a titration feedback. This system has been subject to substantial modeling work, addressing questions about resilience, design and control. The compact core regulatory circuit, as well as its apparent conservation, make this system an ideal 'hydrogen atom' model for the regulation of stress response. Here we take a broad view of the models of the HSR, focusing on the different questions asked and the approaches taken. After 20 years of modeling work, we ask what lessons had been learned that would have been hard to discover without mathematical models. We find that while existing models lay strong foundations, many important questions that can benefit from quantitative modeling are still awaiting investigation.
热休克反应 (HSR) 是一种高度保守的遗传系统，负责保护各种生物和物种中的蛋白质组。自 20 世纪 80 年代初以来的实验已经阐明了这些途径中的关键要素，并揭示了一种典型的调节模式，该模式依赖于滴定反馈。这个系统已经进行了大量的建模工作，解决了关于弹性、设计和控制的问题。这个紧凑的核心调节回路，以及其明显的保守性，使得这个系统成为应激反应调节的理想“氢原子”模型。在这里，我们从广泛的角度来看 HSR 的模型，重点关注提出的不同问题和采用的方法。经过 20 年的建模工作，我们想问一下，如果没有数学模型，很难发现哪些经验教训。我们发现，虽然现有的模型奠定了坚实的基础，但仍有许多可以从定量建模中受益的重要问题有待研究。
