Core Projects & Scientists
Core Projects & Scientists
Transcriptional Robustness of the E. coli Multi-Drug Resistance System To Chemical Challenge
This core research project will examine the dynamics of the multi-drug resistance (MDR) transcriptional network in E. coli as one of the most primitive model system of a stress response network using real-time RNA profiling in single cells.
Structure, and Physiological and Evolutionary Robustness of Stress Response Networks in Eukaryotes
This project will investigate the structure as well as physiological and evolutionary robustness of the conserved heat-shock response in C. elegans and other species of nematodes. In addition to the heat-shock response, the group will construct networks of genes involved in other environmental cues such as heavy metal, UV, nutrient deprivation, osmotic and oxidative stresses. These networks are expected to reveal previously unknown regulatory relationships, identify similarities and differences between networks responsive to different stressors, and uncover conserved and divergent elements of stress responses between distantly related eukaryotes. Finally, the group will use computational and functional comparisons of the cis-regulatory elements of stress response genes from distantly related species of eukaryotes to understand the basic principles of their transcriptional control as well as mechanisms that maintain sensitive and yet highly conserved patterns of gene expression over long periods of evolutionary time.
Dynamics of the Drosophila Segmentation Network, Decoding the Mechanistic Basis of Stability Under Stress and Evolution
This project will combine a multi-level approach to investigate the functional basis for robustness in the Drosophila segmentation network genes. A comprehensive network model of transcription factors controlling the segmentation pathway in Drosophila embryogenesis will be evaluated by combining genomics and evolutionary approaches. In addition, a mathematical modeling of pattern formation by key genes will be used to gain a deeper understanding of mechanisms controlling the robustness of each step in the segmentation pattern formation process.
Drosophila Eye Differentiation: The Yan Network
One of the most well understood transcriptional regulatory networks that responds to cell-cell signaling is the “Yan” network that controls neuronal cell fate in the Drosophila eye. The goal of this core project will be to incorporate single cell analysis with predictive mathematical modeling to determine how the Yan transcription factor network specifies distinct cell fates in the developing Drosophila eye. This will then be extended to study the network’s properties under conditions of signaling perturbation. Importantly, the analysis will consider not only the structural scaffold of transcriptional hierarchies and protein-protein interactions on which the network is based, but will also incorporate the complex patterns of post-translational modifications which constitute an essential but poorly understand component of the networks.
Elucidation of Design Principles, Dynamics and Robustness of Gene Regulatory Networks Orchestrating Hematopoietic Cell Fates
This project will elucidate the complex hematopoietic stem cells regulatory networks that give rise to blood and immune cells and understand their dynamics and robustness at the systems level. We will use a combination of approaches including genome-wide expression and chromatin cross-linking analyses, bioinformatic and high-throughput analyses of cis-elements, shRNA screens and transcription factor perturbations as well as computational and mathematical modeling.
NIGMS