Abstract

We propose to establish an Automation and Imaging Core to provide reagents, instruments, and expertise for protein analysis, image analysis, high throughput screening, and lab automation for the Projects in this program. The Core will leverage staff, lab automation, small molecule screening, RNAi screening, and computational resources from the Harvard Medical School (HMS) ICCB-Longwood Screening Facility. Core B will also provide education and outreach to the Boston scientific community on new assay technologies and best practices in running small molecule and RNAi screens.
Specific Aims for this Core are: 1. Develop standardized methods for quantitative analysis of proteins, including multiplexed bead-based detection methods, in-cell Western assays, and protein antibody arrays. 2. Support high throughput screening of compound libraries and of genome-scale siRNA libraries by the Projects. This includes liquid handling, assay readout, statistical analysis of data, and informatics support. 3. Provide expertise and resources for imaging and image analysis, including support for automated microscopy, obtaining/testing image analysis software, training investigators in the use of analysis software, and development of new image analysis algorithms. 4. Provide lab automation resources and expertise for cell-based and pure protein assays.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA139980-04
Application #
8470480
Study Section
Special Emphasis Panel (ZCA1-RPRB-O)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$214,970
Indirect Cost
$79,433

  Institution

Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Kale, Justin; Kutuk, Ozgur; Brito, Glauber Costa et al. (2018) Phosphorylation switches Bax from promoting to inhibiting apoptosis thereby increasing drug resistance. EMBO Rep 19:
Shi, Jue; Mitchison, Timothy J (2017) Cell death response to anti-mitotic drug treatment in cell culture, mouse tumor model and the clinic. Endocr Relat Cancer 24:T83-T96
Foijer, Floris; Albacker, Lee A; Bakker, Bjorn et al. (2017) Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models of acute T-cell lymphoma and hepatocellular carcinoma. Elife 6:
Fallahi-Sichani, Mohammad; Becker, Verena; Izar, Benjamin et al. (2017) Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state. Mol Syst Biol 13:905
Miller, Miles A; Askevold, Bjorn; Mikula, Hannes et al. (2017) Nano-palladium is a cellular catalyst for in vivo chemistry. Nat Commun 8:15906
Lee, Robin E C; Qasaimeh, Mohammad A; Xia, Xianfang et al. (2016) NF-?B signalling and cell fate decisions in response to a short pulse of tumour necrosis factor. Sci Rep 6:39519
Sarosiek, Kristopher A; Letai, Anthony (2016) Directly targeting the mitochondrial pathway of apoptosis for cancer therapy using BH3 mimetics - recent successes, current challenges and future promise. FEBS J 283:3523-3533
Bhola, Patrick D; Mar, Brenton G; Lindsley, R Coleman et al. (2016) Functionally identifiable apoptosis-insensitive subpopulations determine chemoresistance in acute myeloid leukemia. J Clin Invest 126:3827-3836
Giedt, Randy J; Fumene Feruglio, Paolo; Pathania, Divya et al. (2016) Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response. Sci Rep 6:32985
Flusberg, Deborah A; Sorger, Peter K (2015) Surviving apoptosis: life-death signaling in single cells. Trends Cell Biol 25:446-58

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