Multiscale Models for Synthetic Biology

人类现在可以构建和拼凑DNA序列，以设计新的 生物系统和有机体。我们可以比以往任何时候都更快、更便宜地做到这一点。 我们的合成生物结构的应用比比皆是，从生物化学和生物化学的传感器， 化学武器，去除环境污染物的设备，基因疗法。 合成生物学是一门专注于构建这些新的生物学的学科。 系统.它具有工程学科的所有特征：应用技术和 科学知识，设计和实施设备，系统和过程，安全地实现 一个理想的目标。 数学建模一直是工程学科的重要组成部分。它 可以在合成生物学中发挥重要作用，就像建模在飞机或 架构设计：模型和计算机模拟可以快速提供一个清晰的画面， 不同的组成部分影响整体的行为，迅速达到目标。 拟议的活动将产生建模工具，帮助科学家和工程师 构建复杂的合成生物系统。这些工具将被标准化， 适用于任何合成生物系统。这些活动还将产生新的合成基因 监管网络可以在制药和基因治疗中找到应用。 我们将开发合成生物系统的复杂数学模型， 将目标生物表型（我们希望合成生物系统做的事情）与 DNA序列（我们需要物理构建以实现合成生物学 系统）。我们将对许多替代设计进行模拟，以确定最佳的 分子组成，在我们进入湿实验室之前。然后我们将构建这些 设计在E.大肠杆菌中，并优化它们的性能。 我们建议使用合成的四环素诱导网络，因为它们具有 重要的生物医学应用，主要作为基因治疗表达载体。四环素是一种 小抗生素分子，可以安全地打开任何蛋白质的生产，当这种蛋白质是 在四环素响应性DNA启动子的控制下表达。我们将建模，设计， 构建并测试这些启动子，以确定如何最好地控制蛋白质表达， 四环素诱导

Humans can now construct and piece together DNA sequences in order to design new biological systems and organisms. We can do this more quickly and less expensively than ever. Applications abound for our synthetic biological constructs, from sensors of biochemical and chemical weapons, to devices that will remove environmental pollutants, to gene therapies. Synthetic biology is the discipline that focuses on the construction of these novel biological systems. It has all the characteristic features of an engineering discipline: applying technical and scientific knowledge to design and implement devices, systems, and processes that safely realize a desired objective. Mathematical modeling has always been an important component of engineering disciplines. It can play an important role in synthetic biology the same way modeling helps in aircraft or architecture design: models and computer simulations can quickly provide a clear picture of how different components influence the behavior of the whole, reaching objectives quickly. The proposed activities will result in modeling tools that will help scientists and engineers to construct complex synthetic biological systems. These tools will be standardized, so that they are applicable to any synthetic biological system. The activities will also produce novel synthetic gene regulatory networks that can find applications in pharmaceutical production and gene therapies. We will develop sophisticated mathematical models of synthetic biological systems that connect the targeted biological phenotype (what we want the synthetic biological system to do) to the DNA sequence (that we need to physically construct to realize the synthetic biological system). We will conduct simulations of many alternate designs to decide on the optimum set of molecular components, before we go into the wet laboratory. We will then construct these designs in E. coli and optimize them for performance. We propose to work with synthetic tetracycline inducible networks because they have significant biomedical applications, mainly as gene therapy expression vectors. Tetracycline is a small antibiotic molecule that can safely turn on the production of any protein, when this protein is expressed under the control of a tetracycline-responsive DNA promoter. We will model, design, build and test these promoters to determine how to best control protein expression with tetracycline induction.