Taking advantage of genetic and molecular tagging technologies, cancer research increasingly relies on fluorescence microscopy to study intracellular structures and spatiotemporal regulation of biological processes within cells. A number of supra-molecular structures that regulate cell growth and tissue homeostasis are directly or indirectly affected by cancerous transformation, including the replication machinery of the nucleus, cellular organelles, intercellular adhesion and communication structures, extracellular signaling products, and synaptic recognition by immune cells. Until recently, however, the Abbe's limit of optical diffraction has prevented cell biologists from using fluorescence microscopy to actually observe structures smaller than the half wavelength of light. This application is for funds to purchase the DeltaVision|OMX" super-resolution imaging system which, by overcoming the Abbe's limit of diffraction in up to 4 channels simultaneously, will enable highly detailed investigation of complex subcellular processes. The instrument will greatly enhance a number of cancer-related projects at MD Anderson Cancer Center ranging from basic studies of cell cycle control, to intracellular and intercellular signaling, to immune surveillance and therapy. Each project targets specific hypotheses that require optical imagery at or below 100 nm to resolve molecule location in subcellular structures in sufficient detail. The super-resolution capability in up to four channels will be critical to study colocalization and interactions between several molecules simultaneously. In the long term, the super-resolution capability will help uncover new spatiotemporal biomarkers and therapeutic targets. Important for the goals of the Recovery Act, the DeltaVision|OMX" microscopy system is entirely designed in the United States and its acquisition is predicted to result in job creation and job training. The DeltaVision|OMX structured illumination system will fill a regional void in super-resolution microscopy that is critical for cutting-edge cancer research at MD Anderson.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10RR029552-01
Application #
7840067
Study Section
Special Emphasis Panel (ZRG1-CB-Q (30))
Program Officer
Levy, Abraham
Project Start
2011-06-01
Project End
2012-11-30
Budget Start
2011-06-01
Budget End
2012-11-30
Support Year
1
Fiscal Year
2011
Total Cost
$1,023,721
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Haeusser, Daniel P; Margolin, William (2016) Splitsville: structural and functional insights into the dynamic bacterial Z ring. Nat Rev Microbiol 14:305-19
Haeusser, Daniel P; Rowlett, Veronica W; Margolin, William (2015) A mutation in Escherichia coli ftsZ bypasses the requirement for the essential division gene zipA and confers resistance to FtsZ assembly inhibitors by stabilizing protofilament bundling. Mol Microbiol 97:988-1005
Rowlett, Veronica W; Margolin, William (2015) The bacterial divisome: ready for its close-up. Philos Trans R Soc Lond B Biol Sci 370:
Rowlett, Veronica W; Margolin, William (2015) The Min system and other nucleoid-independent regulators of Z ring positioning. Front Microbiol 6:478
Bartkowiak, Todd; Singh, Shailbala; Yang, Guojun et al. (2015) Unique potential of 4-1BB agonist antibody to promote durable regression of HPV+ tumors when combined with an E6/E7 peptide vaccine. Proc Natl Acad Sci U S A 112:E5290-9
Rowlett, Veronica Wells; Margolin, William (2014) 3D-SIM super-resolution of FtsZ and its membrane tethers in Escherichia coli cells. Biophys J 107:L17-20
Bhatnagar, Parijat; Alauddin, Mian; Bankson, James A et al. (2014) Tumor lysing genetically engineered T cells loaded with multi-modal imaging agents. Sci Rep 4:4502
Brown, Wells S; Khalili, Jahan S; Rodriguez-Cruz, Tania G et al. (2014) B-Raf regulation of integrin α4β1-mediated resistance to shear stress through changes in cell spreading and cytoskeletal association in T cells. J Biol Chem 289:23141-53
Rowlett, Veronica Wells; Margolin, William (2014) Asymmetric constriction of dividing Escherichia coli cells induced by expression of a fusion between two min proteins. J Bacteriol 196:2089-100