Home

Applications

APPLICATIONS OVERVIEW
DRUG DISCOVERY
ADME-Tox
Biochemical Assays
Cell-based Assays
HTS and Secondary Screening
Microsampling
Protein Crystallography
RNAi
Sample Management
CANCER RESEARCH
Personalized Medicine
Functional Screening / DSRT
RNAi
Sequencing
Single-cell Genomics
GENOMIC RESEARCH
Gene Expression
Genotyping
Microbiome
qPCR
Sequencing
Single-cell Genomics
Synthetic Biology

Products

LIQUID HANDLING
LIQUID HANDLERS OVERVIEW
Echo® 525 Liquid Handler
Echo® 555 Liquid Handler
Echo® 550 Liquid Handler
Echo® 520 Liquid Handler
AUTOMATION
AUTOMATION OVERVIEW
Access™ Laboratory Workstation
Tempo™ Automation Control Software
SOFTWARE APPLICATIONS
SOFTWARE OVERVIEW
Echo® Array Maker
Echo® Cherry Pick
Echo® Combination Screen
Echo® Compliance Manager
Echo® Dose-Response
Echo® Plate Audit
Echo® Plate Reformat
CONSUMABLES
CONSUMABLES OVERVIEW
Echo® Qualified Microplates
Labcyte® Assay Microplates
MicroClime® Environmental Lid
Echo® Qualified Reservoir

Technology

Echo® Acoustic Liquid Handling
Dynamic Fluid Analysis™
Acoustic Mass Spectrometry
Direct Dilution

News / Events

Labcyte BLOG
Upcoming Events
Press Releases
Labcyte in the News
Labcyte Community

Resources

JALA Special Issue
Publications
Articles and Other Media
Application Notes
Posters
Webinars
Videos
Customer Profiles
Core Labs

Support

Brochures
Web Documentation*
User Guides*
Quick Start Guides*
Specification Sheets
Site Prep Guides
Service and Maintenance
Request Information

Company

About Us
Echo® Acoustic Technology
Leadership Team
Meet Labcyte
Careers
Contact and Location
Privacy Policy

featuring the Echo® Acoustic Technology
PUBLICATIONS

by scientists and researchers like you

103 Total Publications
HOME | RESOURCES | Publications

PUBLICATIONS

103 Total Publications

REFINE YOUR SEARCH



TITLES and AUTHORS Year Link PDF + Abstract
  • Obtaining genomes from uncultivated environmental microorganisms using FACS-based single-cell genomics Rinke C, Lee J, Nath N, Goudeau D, Thompson B, Poulton N, Dmitrieff E, Malmstrom R, Stepanauskas R a

    Institution: Department of Energy Joint Genome Institute and Bigelow Laboratory for Ocean Sciences

    Publication: Nature Protocols 9, 1038-1048 (2014), doi: 10.1038/nprot.2014.067

    2014 abstract

    Single-cell genomics is a powerful tool for exploring the genetic makeup of environmental microorganisms, the vast majority of which are difficult, if not impossible, to cultivate with current approaches. Here we present a comprehensive protocol for obtaining genomes from uncultivated environmental microbes via high-throughput single-cell isolation by FACS. The protocol encompasses the preservation and pretreatment of differing environmental samples, followed by the physical separation, lysis, whole-genome amplification and 16S rRNA–based identification of individual bacterial and archaeal cells. The described procedure can be performed with standard molecular biology equipment and a FACS machine. It takes <12 h of bench time over a 4-d time period, and it generates up to 1 μg of genomic DNA from an individual microbial cell, which is suitable for downstream applications such as PCR amplification and shotgun sequencing. The completeness of the recovered genomes varies, with an average of ∼50%.

    Publication / Type:
    Nature Protocols 9, 1038-1048 (2014), doi: 10.1038/nprot.2014.067
    Related Subject:
    genomes uncultivated environmental microorganisms FACS-based single-cell genomics
    Link:
    http://www.nature.com/nprot/journal/v9/n5/full/nprot.2014.067.html
  • Identification of Autophosphorylation Inhibitors of the Inositol-Requiring Enzyme 1 Alpha (IRE1α) by High-Throughput Screening Using a DELFIA Assay Newblatt Y, Hardcastle A, McAndrew P C, Strover J A, Mirza A, Morgan G J, Burke R, Davies F E, Colli

    Institution: Institute of Cancer Research

    Publication: Journal of Biomedical Screening, March 2013

    2013 abstract

    Inositol-requiring enzyme 1 alpha (IRE1α) is a transmembrane sensor protein with both kinase and ribonuclease activity, which plays a crucial role in the unfolded protein response (UPR). Protein misfolding in the endoplasmic reticulum (ER) lumen triggers dimerization and subsequent trans-autophosphorylation of IRE1α. This leads to the activation of its endoribonuclease (RNase) domain and splicing of the mRNA of the transcriptional activator XBP1, ultimately generating an active XBP1 (XBP1s) implicated in multiple myeloma survival. Previously, we have identified human IRE1α as a target for the development of kinase inhibitors that could modulate the UPR in human cells, which has particular relevance for multiple myeloma and other secretory malignancies. Here we describe the development and validation of a 384-well high-throughput screening assay using DELFIA technology that is specific for IRE1α autophosphorylation. Using this format, a focused library of 2312 potential kinase inhibitors was screened, and several novel IRE1α kinase inhibitor scaffolds were identified that could potentially be developed toward new therapies to treat multiple myeloma.

    Publication / Type:
    Journal of Biomedical Screening, March 2013
    Related Subject:
    Identification of Autophosphorylation Inhibitors Inositol-Requiring Enzyme 1 Alpha (IRE1α) High-Throughput Screening DELFIA Assay
    Link:
    http://jbx.sagepub.com/content/18/3/298
  • Fueling Open-Source Drug Discovery: 177 Small-Molecule Leads against Tuberculosis Ballell L, Bates R H, Young R J, Alvarez-Gomez D, Alvarez-Ruiz E, Barroso V, Blanco D, Crespo B, Esc

    Institution: GlaxoSmithKline, North Carolina State University

    Publication: ChemMedChem, Volume 8, Issue 2

    2013 abstract

    With the aim of fuelling open-source, translational, early-stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible. A set of 177 potent noncytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead-generation activities. Two additional drug-discovery- relevant datasets are included: a) a drug-like property analysis reflecting the latest lead-like guidelines and b) an early lead-generation package of the most promising hits within the clusters identified.

    Publication / Type:
    ChemMedChem, Volume 8, Issue 2
    Related Subject:
    Tuberculosis
    Link:
    http://onlinelibrary.wiley.com/doi/10.1002/cmdc.201200428/abstract
  • Individualized Systems Medicine (ISM) Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia Pemovska T., Kontro M., Bhagwan Y., Henrik E., Eldfors S., Szwajda A., Almusa H., Bespalov M., Ellon

    Institution: Institute for Molecular Medicine Finland, FIMM, University of Helsinki; La Jolla Laboratories, Pfize

    Publication: Cancer Discovery, Published OnlineFirst September 20, 2013; doi: 10.1158/2159-8290.CD-13-0350

    2013 abstract

    We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one-patient-at-a-time. ISM is based on i) molecular profiling and ex vivo drug sensitivity and resistance testing (DSRT) of patients' cancer cells to 187 oncology drugs, ii) clinical implementation of therapies predicted to be effective and iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered five major taxonomic drug response subtypes based on DSRT profiles, some with distinct genomic features (e.g. MLL gene fusions in subgroup IV and FLT3-ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. After progression under DSRT-guided therapies, AML cells displayed significant clonal evolution, novel genomic changes potentially explaining resistance, while ex vivo DSRT data showed resistance to the clinically applied drugs and new vulnerabilities to previously ineffective drugs.

    Publication / Type:
    Cancer Discovery, Published OnlineFirst September 20, 2013; doi: 10.1158/2159-8290.CD-13-0350
    Related Subject:
    Individualized Systems Medicine (ISM) Strategy Chemorefractory Acute Myeloid Leukemia
    Link:
    http://cancerdiscovery.aacrjournals.org/content/early/2013/09/18/2159-8290.CD-13-0350
  • Target Inhibition Networks: Predicting Selective Combinations of Druggable Targets to Block Cancer Survival Pathways Tang, J, Karhinen L, Xu T, Szwajda A, Yadav B, Wennerberg K, Aittokallio T

    Institution: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

    Publication: PLoS Comput Biol 9(9): e1003226. doi:10.1371/journal.pcbi.1003226

    2013 PDF abstract

    A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alternatives on a global network level. We took a functional systems pharmacology approach toward the identification of selective target combinations for specific cancer cells by combining large-scale screening data on drug treatment efficacies and drug-target binding affinities. Our model-based prediction approach, named TIMMA, takes advantage of the polypharmacological effects of drugs and infers combinatorial drug efficacies through system-level target inhibition networks. Case studies in MCF-7 and MDA-MB-231 breast cancer and BxPC-3 pancreatic cancer cells demonstrated how the target inhibition modeling allows systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways in a given cancer type. The TIMMA prediction results were experimentally validated by means of systematic siRNA-mediated silencing of the selected targets and their pairwise combinations, showing increased ability to identify not only such druggable kinase targets that are essential for cancer survival either individually or in combination, but also synergistic interactions indicative of nonadditive drug efficacies. These system-level analyses were enabled by a novel model construction method utilizing maximization and minimization rules, as well as a model selection algorithm based on sequential forward floating search. Compared with an existing computational solution, TIMMA showed both enhanced prediction accuracies in cross validation as well as significant reduction in computation times. Such cost-effective computational-experimental design strategies have the potential to greatly speed-up the drug testing efforts by prioritizing those interventions and interactions warranting further study in individual cancer cases.

    Publication / Type:
    PLoS Comput Biol 9(9): e1003226. doi:10.1371/journal.pcbi.1003226
    Related Subject:
    Target Inhibition Networks Druggable Targets Cancer Survival Pathways
    Link:
    http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003226
  • An HTS-Compatible 3D Colony Formation Assay to Identify Tumor-Specific Chemotherapeutics Horman S, To J, Orth A

    Institution: Genomics Institute of the Novartis Research Foundation (GNF)

    Publication: J Biomol Sc high-content screening, HTS, colon, colony formation, soft agar, co-culture, 3D assay de

    2013 abstract

    There has been increasing interest in the development of cellular behavior models that take advantage of three-dimensional (3D) cell culture. To enable assessment of differential perturbagen impacts on cell growth in 2D and 3D, we have miniaturized and adapted for high-throughput screening (HTS) the soft agar colony formation assay, employing a laserscanning cytometer to image and quantify multiple cell types simultaneously. The assay is HTS compatible, providing high-quality, image-based, replicable data for multiple, co-cultured cell types. As proof of concept, we subjected colorectal carcinoma colonies in 3D soft agar to a mini screen of 1528 natural product compounds. Hit compounds from the primary screen were rescreened in an HTS 3D co-culture matrix containing colon stromal cells and cancer cells. By combining tumor cells and normal, nontransformed colon epithelial cells in one primary screening assay, we were able to obtain differential IC50 data, thereby distinguishing tumor-specific compounds from general cytotoxic compounds. Moreover, we were able to identify compounds that antagonized tumor colony formation in 3D only, highlighting the importance of this assay in identifying agents that interfere with 3D tumor structural growth. This screening platform provides a fast, simple, and robust method for identification of tumor-specific agents in a biologically relevant microenvironment.  

    Publication / Type:
    J Biomol Sc high-content screening, HTS, colon, colony formation, soft agar, co-culture, 3D assay de
    Related Subject:
    HTS-Compatible 3D Colony Formation Assay Tumor-Specific Chemotherapeutics
    Link:
    http://jbx.sagepub.com/content/early/2013/08/05/1087057113499405
  • Is Your Liquid Handling Misleading You? Olechno J

    Institution: Labcyte Inc., Institute for Molecular Medicine Finland, FIMM, University of Helsinki

    Publication: Innovations in Pharmaceutical Technology June 2013 Issue 45 31-35 

    2013 abstract

    Selecting the most suitable liquid handling method can have a huge influence over your final results, particularly with miniaturised volumes. Acoustic liquid handling using the relatively new direct dilution technique may offer scientists greater accuracy.

    Publication / Type:
    Innovations in Pharmaceutical Technology June 2013 Issue 45 31-35 
    Related Subject:
    Serial dilution, Acoustic liquid handling, Dimethyl sulfoxide (DMSO), Pharmacophore
    Link:
    http://www.iptonline.com/pdf_viewarticle.asp?cat=3&article=915
  • Dispensing Processes Impact Apparent Biological Activity as Determined by Computational and Statistical Analyses Ekins S, Olechno J, Williams AJ

    Institution: Collaborations in Chemistry, Labcyte Inc., Royal Society of Chemistry

    Publication: PLoS ONE 8(5): e62325, 2013. http://doi:10.1371/journal.pone.0062325

    2013 PDF abstract

    Dispensing and dilution processes may profoundly influence estimates of biological activity of compounds. Published data show Ephrin type-B receptor 4 IC50 values obtained via tip-based serial dilution and dispensing versus acoustic dispensing with direct dilution differ by orders of magnitude with no correlation or ranking of datasets. We generated computational 3D pharmacophores based on data derived by both acoustic and tip-based transfer. The computed pharmacophores differ significantly depending upon dispensing and dilution methods. The acoustic dispensing-derived pharmacophore correctly identified active compounds in a subsequent test set where the tip-based method failed. Data from acoustic dispensing generates a pharmacophore containing two hydrophobic features, one hydrogen bond donor and one hydrogen bond acceptor. This is consistent with X-ray crystallography studies of ligand-protein interactions and automatically generated pharmacophores derived from this structural data. In contrast, the tip-based data suggest a pharmacophore with two hydrogen bond acceptors, one hydrogen bond donor and no hydrophobic features. This pharmacophore is inconsistent with the X-ray crystallographic studies and automatically generated pharmacophores. In short, traditional dispensing processes are another important source of error in high-throughput screening that impacts computational and statistical analyses. These findings have far-reaching implications in biological research.

    Publication / Type:
    PLoS ONE 8(5): e62325, 2013. http://doi:10.1371/journal.pone.0062325
    Related Subject:
    Dispensing Processes Impact Apparent Biological Activity Computational Statistical Analyses
    Link:
    http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0062325
  • High-Throughput RNA Interference Screening: Tricks of the Trade Nebane MN, Coric T, Whig K, McKellip S, Woods L, Sosa M, Sheppard R, Rasmussen L, Bjornsti M, White

    Institution: Southern Research Institute, University of Alabama at Birmingham

    Publication: Journal of Laboratory Automation April 24, 2013 2211068213486786

    2013 abstract

    The process of validating an assay for high-throughput screening (HTS) involves identifying sources of variability and developing procedures that minimize the variability at each step in the protocol. The goal is to produce a robust and reproducible assay with good metrics. In all good cell-based assays, this means coefficient of variation (CV) values of less than 10% and a signal window of fivefold or greater. HTS assays are usually evaluated using Z′ factor, which incorporates both standard deviation and signal window. A Z′ factor value of 0.5 or higher is acceptable for HTS. We used a standard HTS validation procedure in developing small interfering RNA (siRNA) screening technology at the HTS center at Southern Research. Initially, our assay performance was similar to published screens, with CV values greater than 10% and Z′ factor values of 0.51 ± 0.16 (average ± standard deviation). After optimizing the siRNA assay, we got CV values averaging 7.2% and a robust Z′ factor value of 0.78 ± 0.06 (average ± standard deviation). We present an overview of the problems encountered in developing this whole-genome siRNA screening program at Southern Research and how equipment optimization led to improved data quality.

    Publication / Type:
    Journal of Laboratory Automation April 24, 2013 2211068213486786
    Related Subject:
    High-Throughput RNA Interference Screening Trade
    Link:
    http://jla.sagepub.com/content/early/2013/04/23/2211068213486786.abstract
  • Structural Basis of Signaling Blockade by Anti-IL-13 Antibody Lebrikizumab Ultsch M, Bevers J, Nakamura G, Vandlen R, Kelley RF, Wu LC, Eigenbrot C.

    Institution: Genentech Inc.

    Publication: J Molecular Biology, 425 (8) 1330–1339, 2013.

    2013 abstract

    The cytokine interleukin 13 (IL-13) is a major effector molecule for T-helper type 2 inflammation and is pathogenic in allergic diseases such as asthma. The effects of IL-13 are mediated via a pathway that is initiated by binding to a heterodimeric receptor consisting of IL-13Rα1 and IL-4Rα. Antibodies raised against IL-13 can block its inflammatory effects by interfering with binding to either of the two receptor polypeptides. Lebrikizumab is a monoclonal anti-IL-13 antibody that has shown clinical benefit in a phase II study for the treatment of moderate-to-severe uncontrolled asthma. Here we report the molecular structure of IL-13 in complex with the Fab from lebrikizumab by X-ray crystallography at 1.9 Å resolution. We show that lebrikizumab inhibits IL-13 signaling by binding to IL-13 with very high affinity and blocking IL-13 binding to IL-4Rα. In addition, we use site-directed mutations to identify the most important antibody contributors to binding. Our studies define key features of lebrikizumab binding and its mechanism of action that may contribute to its clinical effects.

    Publication / Type:
    J Molecular Biology, 425 (8) 1330–1339, 2013.
    Related Subject:
    Signaling Blockade Anti-IL-13 Antibody Lebrikizumab
    Link:
    http://dx.doi.org/10.1016/j.jmb.2013.01.024
EXPAND ABSTRACTS




Featured Labcyte Downloads
For Research Use Only Not for use in Diagnostics
TOP