(application abstract) ? Perturbations in the homeostasis of cells by invading organisms, accumulation of pathologic substances, and uncontrolled cell growth provide the underlying basis for most morbid and mortal illness. As such, the challenge of manipulating cellular functions for desired outcomes, such as cancer eradication, controlling viral infection onset as well as stem cell differentiation collectively toward therapeutic gain lies within the complexity of the system of regulatory circuitries that govern cellular pheno-/genotypes. The goal for this center is to investigate and manipulate the complex cell signaling network circuitries in a time-resolved dynamic manner in order to not only enhance our understanding of individual signaling pathways but also provide vital information on their codependence and interactivities for the potential of controlling the cell phenotype. Our unique approach employs a systemic view of controlling networks that has the ability to i) perturb the cellular network circuitry, ii) conduct real time monitoring of the key signaling elements, iii) interpret and analyze the system's response, and iv) use a global system control algorithm to dissect and analyze the cellular network circuitry. This approach precisely addresses the NIH's vision on NDC that """"""""decisions on the biological systems...guided by the principle that the precise control required to manipulate cellular components will depend upon understanding and using engineering principles"""""""". Our objective is not only to extend our understandings of local interactions of cellular components but also globally control cellular functions through regulatory circuitries. Unbalanced signaling pathway, triggered by either external or internal factors, is the hallmark of human disease. This is especially true for conditions like cancers, infectious diseases and stem cell related disorders. This center proposes unique techniques to explore the dynamics of the signaling pathways in these three fields and to dynamically control the outcomes of the network for novel therapeutics. ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Development Center (PN2)
Project #
1PN2EY018228-01
Application #
7252933
Study Section
Special Emphasis Panel (ZEY1-VSN (13))
Program Officer
Fisher, Richard S
Project Start
2006-09-30
Project End
2011-09-29
Budget Start
2006-09-30
Budget End
2007-09-29
Support Year
1
Fiscal Year
2006
Total Cost
$700,000
Indirect Cost
Name
University of California Los Angeles
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Spitzer, Matthew H; Gherardini, Pier Federico; Fragiadakis, Gabriela K et al. (2015) IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system. Science 349:1259425
Angelo, Michael; Bendall, Sean C; Finck, Rachel et al. (2014) Multiplexed ion beam imaging of human breast tumors. Nat Med 20:436-42
Labno, Anna; Warrier, Ajithkumar; Wang, Sheng et al. (2014) Local plasticity of dendritic excitability can be autonomous of synaptic plasticity and regulated by activity-based phosphorylation of Kv4.2. PLoS One 9:e84086
Sen, Nandini; Mukherjee, Gourab; Sen, Adrish et al. (2014) Single-cell mass cytometry analysis of human tonsil T cell remodeling by varicella zoster virus. Cell Rep 8:633-45
Bruggner, Robert V; Bodenmiller, Bernd; Dill, David L et al. (2014) Automated identification of stratifying signatures in cellular subpopulations. Proc Natl Acad Sci U S A 111:E2770-7
Zangle, Thomas A; Teitell, Michael A (2014) Live-cell mass profiling: an emerging approach in quantitative biophysics. Nat Methods 11:1221-8
Teh, Boon Eng; French, Christopher Todd; Chen, Yahua et al. (2014) Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NF?B. BMC Microbiol 14:115
Ding, Xianting; Liu, Ningxia; Matsuo, Kyle et al. (2014) Use of cell morphology as early bioindicator for viral infection. IET Nanobiotechnol 8:24-30
Bendall, Sean C; Davis, Kara L; Amir, El-Ad David et al. (2014) Single-cell trajectory detection uncovers progression and regulatory coordination in human B cell development. Cell 157:714-25
Yamane, Daisuke; Wu, Yi-Chien; Wu, Ting-Hsiang et al. (2014) Electrical impedance monitoring of photothermal porated mammalian cells. J Lab Autom 19:50-9

Showing the most recent 10 out of 95 publications