The University of New Mexico Center for Molecular Discovery (UNMCMD), a specialty center focusing on multiplexed, HT flow cytometry, continues the New Mexico Molecular Libraries Screening Center (U54MH074425) and a Biomedical Research Partnership (R24EB000264). We invented the HT flow cytometry platform HyperCyt? and introduced it to the MLSCN. Our discovery tools enable homogeneous analysis of ligand binding and/or protein-protein interaction (PPI), multiparameter or high content analysis, and real-time measurements of cell response or binding. We analyze a 384 well plate in 11 min. Completed screens on the MLSMR have produced probes for cell (molecular and phenotypic) and bead-based targets. Experience indicates that most targets can be displayed in a flow cytometry compatible format. By creating a suspension array of particles, targets can be highly multiplexed or performed on complex cell populations without loss of throughput. Our team has produced >100 publications, >20 inventions, books on Flow Cytometry for Biotechnology and Virtual Screening, and >100 oral outreach presentations world-wide. We have >150 years of flow cytometry experience that includes applications in biochemistry, and cell and molecular biology compatible with a dual specialization in yeast targets. One of us has >20 years of experience in industrial HTS for >150 novel targets. We have core capabilities that include 1) effective outreach and partnership;2) identifying and developing innovative targets;3) implementing external primary and secondary assays;4) production mode screening of multiplexed targets;and 5) data upload to PubChem. We are uniquely positioned to integrate imaging agents and isotopes into the MLPCN. We intend to innovate in all of our activities. Through outreach, we will create and maintain a pipeline of multiplex assays for the MLPCN. Assay development will include, but not be limited to, yeast, eukaryotic, and profiling targets. We will create mechanisms to prioritize and implement partnerships for profiling targets and probes, including compound solubility, for the MLPCN. We will create tools to analyze and visualize multiplex HTS data sets. We will enhance and maintain collaborative tools for networking with target providers and Chemistry Specialty Centers for screening and follow up, and within the MLPCN for collaborative profiling and compound solubility. One Center Driven Project focuses on increasing throughput (from 384 to 1536 well format) and improving the performance of HT flow cytometry by exploiting recent design and engineering breakthroughs in our Center along with commercial partners. Through collaborative outreach, we will evaluate new discovery technologies emerging from the Los Alamos National Labs P41 National Flow Cytometry Resource. A second Center Driven Project develops a toolbox for yeast targets such as PPI, Pathway analysis, protein-DNA interactions, and a universal, multiplex yeast two-hybrid discovery platform.

Public Health Relevance

Novel high throughput flow cytometry technology will be used for the discovery of small molecules that can serve as probes, imaging agents and leads in discovery for multiplexed biological targets. A pipeline of targets will developed through active outreach and consortium building efforts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
3U54MH084690-04S2
Application #
8704042
Study Section
Special Emphasis Panel (ZRG1-IFCN-K (52))
Program Officer
Brady, Linda S
Project Start
2008-09-01
Project End
2014-05-31
Budget Start
2013-08-19
Budget End
2014-05-31
Support Year
4
Fiscal Year
2013
Total Cost
$799,999
Indirect Cost
$214,199
Name
University of New Mexico Health Sciences Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Wu, Yang; Tapia, Phillip H; Jarvik, Jonathan et al. (2014) Real-time detection of protein trafficking with high-throughput flow cytometry (HTFC) and fluorogen-activating protein (FAP) base biosensor. Curr Protoc Cytom 67:Unit 9.43.
Chigaev, Alexandre; Smagley, Yelena; Sklar, Larry A (2014) Carbon monoxide down-regulates ?4?1 integrin-specific ligand binding and cell adhesion: a possible mechanism for cell mobilization. BMC Immunol 15:52
Sully, Erin K; Malachowa, Natalia; Elmore, Bradley O et al. (2014) Selective chemical inhibition of agr quorum sensing in Staphylococcus aureus promotes host defense with minimal impact on resistance. PLoS Pathog 10:e1004174
Tegos, George P; Evangelisti, Annette M; Strouse, J Jacob et al. (2014) A high throughput flow cytometric assay platform targeting transporter inhibition. Drug Discov Today Technol 12:e95-103
Bernardo, Stella M; Allen, Christopher P; Waller, Anna et al. (2014) An automated high-throughput cell-based multiplexed flow cytometry assay to identify novel compounds to target Candida albicans virulence-related proteins. PLoS One 9:e110354
Wu, Yang; Tapia, Phillip H; Fisher, Gregory W et al. (2013) High-throughput flow cytometry compatible biosensor based on fluorogen activating protein technology. Cytometry A 83:220-6
Sirenko, Oksana; Crittenden, Carole; Callamaras, Nick et al. (2013) Multiparameter in vitro assessment of compound effects on cardiomyocyte physiology using iPSC cells. J Biomol Screen 18:39-53
Chibebe Junior, Jose; Sabino, Caetano P; Tan, Xiaojiang et al. (2013) Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella. BMC Microbiol 13:217
Pinilla, Clemencia; Edwards, Bruce S; Appel, Jon R et al. (2013) Selective agonists and antagonists of formylpeptide receptors: duplex flow cytometry and mixture-based positional scanning libraries. Mol Pharmacol 84:314-24
Strouse, J Jacob; Ivnitski-Steele, Irena; Waller, Anna et al. (2013) Fluorescent substrates for flow cytometric evaluation of efflux inhibition in ABCB1, ABCC1, and ABCG2 transporters. Anal Biochem 437:77-87

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