Mathematical Modeling and Computer Simulation for Gene Expression and Regulation

该项目的总体目标是在密歇根州立大学建立数学家和实验生物学家之间的研究合作，并培养研究生在跨学科领域进行研究。该项目是由PI与密歇根州立大学生物化学和分子生物学系的分子遗传学领先科学家David N. Arnosti教授合作。最初的重点领域将是基因表达和调控的数学建模和计算机模拟。当代基因调控研究的一个关键目标是在定量水平上了解转录装置的活性。该项目的中心目标是将建模方法与果蝇胚皮胚胎中一组相对较好表征的转录调节因子的转录开关活性的定量测定相结合。与目前其他将基因开关视为黑盒子的高水平网络方法不同，该项目是详细研究在增强子内激活位点块的背景下影响转录抑制子功效的顺式调控规则。转录调控的建模将有助于对转录调控机制的机制理解，为基因调控元件和网络的进化提供新的见解，并将为预测顺式调控元件的定量输出提供工具。该IGMS项目由MPS多学科活动办公室（OMA）和数学科学司（DMS）联合支持。

The general goal of this project is to establish research collaborations between mathematicians and experimental biologists at the Michigan State University and to train the graduate students in doing research in interdisciplinary fields. The proposed project is for the PI to work with Professor David N. Arnosti, a leading scientist in Molecular Genetics, at the Department of Biochemistry and Molecular Biology, Michigan State University. The initial area of focus would be mathematical modeling and computer simulation for gene expression and regulation. A key objective of contemporary gene regulatory studies is to understand the activity of the transcriptional apparatus at a quantitative level. The central goal of this project is to meld modeling approaches with quantitative determinations of transcriptional switch activity for a limited set of relatively well-characterized transcriptional regulators in the Drosophila blastoderm embryo. Unlike other current high level network approaches that treat gene switches as black boxes, this project is to study in details the cis regulatory rules that affect the efficacy of transcriptional repressors in the context of blocks of activator sites within enhancer. The modeling of transcriptional regulation will aid mechanistic understanding of transcriptional regulatory mechanisms, provide new insights on the evolution of gene regulatory elements and networks, and will supply tools for predicting the quantitative output of cis regulatory elements.This IGMS project is jointly supported by the MPS Office of Multidisciplinary Activities (OMA) and the Division of Mathematical Sciences (DMS).