Research Initiation Award Grant: Modeling and Control Genetic Regulations in Biological Networks using Advanced Signal Processing and Control Theory

该项目的总体目标是为基因调控的建模和控制提供一个理论和计算框架，以产生针对癌症等遗传性疾病的有效治疗策略。对癌细胞等遗传病理细胞的这种干预的完成，将是医学向基于动态分子相互作用的数学基础的工程学科转变的重要一步。该项目的教育目标是加强PVAMU工程学学生的素质教育，并增加从事计算和系统生物学职业的非裔美国学生的数量。该项目每年将资助三名本科生从事这项研究。此外，许多学生将受到一门新课程和几门强化课程的影响。这个项目的跨学科性质承诺通过研究和教育促进电气工程和系统生物学之间的思想交流。该项目旨在利用混合系统模拟药物对基因调控的影响，并根据其复杂的性质--关于网络动力学、稳健性和敏感性--推断其目标基因调控网络，从而设计更好的干预策略。与传统技术(如在某个时间点提供系统某一方面的快照的微阵列)不同，肿瘤细胞对药物的反应可以通过药物扰动对细胞反应的多维检查来定量表征，以测试细胞类型、报告人员和药物/剂量的不同组合，并通过旨在更好地了解遗传调控网络行为的系统识别和控制理论方法来增强，以便设计有效的治疗策略。

The overarching goal of this project is to provide a theoretical and computational framework for modeling and control of genetic regulation to generate effective therapeutic strategies for genetic diseases such as cancer. The accomplishment of such intervention in genetically pathological cells, such as cancer cells, would be a major step in the transformation of medicine to a mathematically grounded engineering discipline based on dynamic molecular interaction. The education goal of this project is to enhance the quality education for engineering students at PVAMU and to increase the number of African-American students pursuing careers in computational and systems biology. Three undergraduate students will be supported by this project each year to work on the research. In addition, many students will be impacted by a new course and several enhanced courses.The interdisciplinary nature of this project promises to foster crossfertilization of ideas between electrical engineering and systems biology through research and education. The project aims to model drug effects on gene regulation using hybrid systems and infer their targeted genetic regulatory networks in terms of their complex nature - in regard to network dynamics, robustness and sensitivity - thereby designing better intervention strategies. Instead of traditional techniques, such as microarrays that provide a snapshot of an aspect of the system at one time point, the dynamics of tumor cell response to drugs can be quantitatively characterized through a multi-dimensional examination of the cells' responses through drug perturbation to test different combinations of cell type, reporters, and drugs/dosages, augmented by a system identification and control theoretical approach aiming to better understand genetic regulatory network behavior in order to design effective therapeutic strategies.