Biswas Surama, Manicka Santosh, Hoel Erik, Levin Michael
Allen Discovery Center, Tufts University, Medford, MA, USA.
Wyss Institute for Biologically Inspired Engineering at Harvard University, Cambridge, MA, USA.
iScience. 2021 Feb 1;24(3):102131. doi: 10.1016/j.isci.2021.102131. eCollection 2021 Mar 19.
Gene regulatory networks (GRNs) process important information in developmental biology and biomedicine. A key knowledge gap concerns how their responses change over time. Hypothesizing long-term changes of dynamics induced by transient prior events, we created a computational framework for defining and identifying diverse types of memory in candidate GRNs. We show that GRNs from a wide range of model systems are predicted to possess several types of memory, including Pavlovian conditioning. Associative memory offers an alternative strategy for the biomedical use of powerful drugs with undesirable side effects, and a novel approach to understanding the variability and time-dependent changes of drug action. We find evidence of natural selection favoring GRN memory. Vertebrate GRNs overall exhibit more memory than invertebrate GRNs, and memory is most prevalent in differentiated metazoan cell networks compared with undifferentiated cells. Timed stimuli are a powerful alternative for biomedical control of complex dynamics without genomic editing or transgenes.
基因调控网络(GRNs)在发育生物学和生物医学中处理重要信息。一个关键的知识空白涉及它们的反应如何随时间变化。假设由短暂的先前事件引起的动力学长期变化,我们创建了一个计算框架,用于定义和识别候选基因调控网络中不同类型的记忆。我们表明,来自广泛模型系统的基因调控网络预计具有多种类型的记忆,包括巴甫洛夫条件反射。关联记忆为具有不良副作用的强效药物的生物医学应用提供了一种替代策略,也是理解药物作用的变异性和时间依赖性变化的一种新方法。我们发现了有利于基因调控网络记忆的自然选择证据。脊椎动物的基因调控网络总体上比无脊椎动物的基因调控网络表现出更多的记忆,并且与未分化细胞相比,记忆在分化的后生动物细胞网络中最为普遍。定时刺激是一种强大的替代方法,可用于在不进行基因组编辑或转基因的情况下对复杂动力学进行生物医学控制。