Terminal cellular differentiation is often coupled with a halt in proliferation and permanent exit from the cell cycle. A loss of coordination between these processes can lead to aberrant tissue development and tumorigenesis. Despite its importance, little is known about how cell cycle exit and terminal differentiation are coordinated. One hypothesis, supported by studies in cell culture, mice and insects, suggests that the extracellular signals that trigger differentiation also control the expression of key cell cycle regulators. However, the identities of these regulators and the genetic regulatory networks linking extracellular differentiation signals with cell cycle genes remain largely unknown. To identify the gene regulatory networks linking terminal differentiation with cell cycle exit in vivo, this collaborative pilot project between Dr. Edgar at FHCRC and Dr. Song at NMSU proposes to combine a novel systems biology approach through discrete dynamic system models with high throughput temporal gene expression and reverse genetics studies in the successful model organism, Drosophila melanogaster. These models will allow one to predict genetic networks that connect extracellular signals with the cell cycle machinery. The models will be tested and explored by experiments in vivo. This project has three specific aims:
Aim 1. To advance the methodology and software to generate discrete dynamic system models from genomewide temporal gene expression. Microarray data from Drosophila wings will be used.
Aim 2. To test the modeling approach by genetic perturbations in silico and comparing the predicted changes in gene expression to the changes experimentally observed in vivo.
Aim 3. To use the modeling approach to predict new genetic regulatory networks converging on cell cycle control during differentiation, and experimentally explore and validate the predicted networks in vivo. Importantly, the aims are highly iterative and will lead to a close integration and cooperation between the in vivo experiments at FHCRC and in silico modeling at NMSU. These investigations will ultimately provide information about how developmental signals interface with the cell cycle to ensure cell cycle exit upon terminal differentiation. In addition, a powerful and widely applicable computational approach to elucidating gene regulatory networks will be developed.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1)
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New Mexico State University Las Cruces
Las Cruces
United States
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Molina, Yamile; Briant, Katherine J; Sanchez, Janeth I et al. (2018) Knowledge and social engagement change in intention to be screened for colorectal cancer. Ethn Health 23:461-479
Ortega, Sigolène; McAlvain, Megan Stamey; Briant, Katherine J et al. (2018) Perspectives of Community Advisory Board Members in a Community-Academic Partnership. J Health Care Poor Underserved 29:1529-1543
Sanchez, N S; Quinn, K E; Ashley, A K et al. (2018) In the ovine pituitary, CXCR4 is localized in gonadotropes and somatotropes and increases with elevated serum progesterone. Domest Anim Endocrinol 62:88-97
Gurley, Kay E; Ashley, Amanda K; Moser, Russell D et al. (2017) Synergy between Prkdc and Trp53 regulates stem cell proliferation and GI-ARS after irradiation. Cell Death Differ 24:1853-1860
Phan, Tuan Anh; Tian, Jianjun Paul (2017) The Role of the Innate Immune System in Oncolytic Virotherapy. Comput Math Methods Med 2017:6587258
Quinn, K E; Reynolds, L P; Grazul-Bilska, A T et al. (2016) Placental development during early pregnancy: Effects of embryo origin on expression of chemokine ligand twelve (CXCL12). Placenta 43:77-80
Salazar, Monica; Lerma-Ortiz, Alejandra; Hooks, Grace M et al. (2016) Progestin-mediated activation of MAPK and AKT in nuclear progesterone receptor negative breast epithelial cells: The role of membrane progesterone receptors. Gene 591:6-13
Adams, Scott V; Barrick, Brian; Christopher, Emily P et al. (2016) Urinary heavy metals in Hispanics 40-85 years old in Doña Ana County, New Mexico. Arch Environ Occup Health 71:338-346
Cao, Ruofan; Jenkins, Patrick; Peria, William et al. (2016) Phasor plotting with frequency-domain flow cytometry. Opt Express 24:14596-607
Qian, Lei; Bradford, Andrew M; Cooke, Peter H et al. (2016) Grb7 and Hax1 may colocalize partially to mitochondria in EGF-treated SKBR3 cells and their interaction can affect Caspase3 cleavage of Hax1. J Mol Recognit 29:318-33

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