UBM-Group: Studying Cell Response to Input Signals as the Basis for Interdisciplinary Training for Undergraduates in Biological and Mathematical Sciences

该项目的主要目标是增加追求科学事业的学生人数，有效地将数学和生物科学结合起来。这两个领域的整合将基于哺乳动物细胞的应激反应系统和大肠杆菌的铁摄取系统。应激反应系统是生物学的核心，因为它保护细胞免受环境的剧烈变化。本项目将利用随机非线性基因调控网络理论，为在分子水平上理解应力现象增加一个新的维度。该项目还包括由大肠杆菌中的铁调节的生物过程的数学和实验方面。机体对铁缺乏的反应通常是增加吸收铁的能力和消耗细胞内储存的铁。虽然细菌中的铁调节系统与哺乳动物细胞的应激反应不同，但学生们将认识到数学问题将这些项目统一起来。学生在这个项目中使用的数学理论为创建遗传电路设计算法提供了一种很有前途的方法，这是我们下一代科学家的关键领域。该项目建立在这样一个理念之上，即为了对数学和生物学交叉领域的联合研究项目做出充分贡献，数学专业的本科生必须克服他们可能对在“潮湿”的实验室中工作的担忧，生物学专业的学生必须克服他们可能对数学研究的担忧。尽管某些学生对在潮湿的实验室工作感到不安，但我们发现，有数学倾向的学生在挑战遵循构成任何分子生物学试验核心的非常精确的步骤序列时表现良好。因此，我们认为，对于一个以数学为导向的人来说，进入生物学的途径是在本科阶段尽快沉浸在潮湿的实验室环境中。对数学敏感的生物学学生采取的方法是告诉他们数学作为假设的丰富来源是有用的。在生物学家的手中，这个假设可以导致新的有价值的实验设计。生物学学生的目标应该是能够阅读象征性的数学信息，并将其与潜在的生物学模型联系起来。

The main objective of this project is to increase the number of students who will pursue scientific careers that effectively integrate the mathematical and biological sciences. The integration of these two areas will be based on the stress response system in mammalian cells and on iron uptake system in E. coli. The stress response system is central in biology, since it protects the cell against dramatic changes in the environment. This project will add a new dimension towards understanding stress phenomena at a molecular level by using a theory of stochastic nonlinear gene regulatory networks. The project also includes mathematical and experimental aspects of biological processes that are regulated by iron in the E. coli bacterium. Organisms generally respond to iron deficiency by increasing their capacity to take up iron and by consuming intracellular iron stores. While the iron-regulated system in bacteria is different from that of the stress response in mammalian cells, students will recognize that mathematical questions unify the projects. The mathematical theory used by students in this project offers a promising way to create algorithms for genetic circuitry design, a critical area for our next generation of scientists. The project builds upon the idea that to fully contribute to a joint research project at the intersection of mathematics and biology, undergraduates in mathematics must overcome apprehensions they may have about working in a "wet" lab and biology students must overcome apprehensions they may have about mathematical studies.In spite of the uneasiness among certain students of working in a wet lab, we have found that mathematically inclined students perform well when they are challenged to follow a very precise sequence of steps that constitutes the core of any molecular biology assay. We thus believe that the route for a mathematically-oriented person to get involved into biology is to be immersed in a wet lab environment as soon as possible at undergraduate level. The approach taken for the mathematics-apprehensive biology students is to teach them that mathematics is useful as a rich source of hypothesis. In the hands of biologists, this hypothesis can lead to new valuable experimental designs. The goal for the biology students should be to become capable of reading the symbolic mathematical information and correlating it with the underlying biological model.