Services Offered



We provide a wide variety of services associated with lab automation and high-throughput technologies aimed at screening purposes or, more generally, large-scale experimental procedures. Initially, we will require from users a detailed description of their research program, including, but not limited to, a comprehensive overview of the biological system investigated, the overall objectives pursued, preliminary data, estimated timelines, budgetary considerations and availability of funds and, finally, distribution of roles and responsibilities. Services can be listed and briefly described as follows:



I. Assay Design


We provide consultation on the assay design that is the most suitable to address the biological question asked by the user. To this end, the first step typically consists of assessing the screenability of the biological system. Should a given system be considered screenable, we will provide proven expertise to define a cell-free or cell-based assay method with the most convenient and effective combination of features, such as sensitivity, reproducibility, selectivity, speed, and costs. This process is strongly facilitated by our capability to precisely perform multi-step procedures (including separation and ultrafiltration steps) and achieve the widest arrays of detection modes (both as endpoint or kinetic) for assay measurements, which include absorbance, fluorescence, time-resolved fluorescence (TRF), fluorescence polarization (FP), fluorescence resonance energy transfer (FRET), time-resolved FRET (TRF-FRET), bioluminescence resonance energy transfer (BRET), and luminescence.

Our personnel may review and assess, if available, preliminary data to determine whether a benchtop assay protocol may be adapted to high-throughput conditions. To this end, screening parameters as well as budgetary and logistic issues are properly evaluated prior to finalization. If necessary, miniaturization strategies or alternative assay procedures (either direct or indirect) may be proposed and carefully appraised for benefits, drawbacks and overall risks.


II. Access to Screening Reagents

Compound collections have been acquired from commercial sources and through collaborative programs with other Institutes to tackle specific screening rationales, namely i) the identification of chemical rings or pharmacophores with biochemical, biological or pharmacological properties; ii) the elucidation of molecular mechanisms or signaling pathways associated with a given cell phenotype; and iii) the discovery of innovative or repositioned drugs. To these ends, we can provide access to the following collections:


Chemical libraries

  • Approximately 220,000 drug-like chemicals, obtained from several vendors (Maybridge, Chembridge, Asinex, Enamine), designed through computational screens in order to provide lead-like motifs and minimize promiscuous hitters while enhancing chemical diversity;
  • 4000 semi-natural compounds to explore chemical space around natural motifs (that is, small molecules decorated around 8 natural scaffolds (500 molecules per scaffold such as (i) quinic acid and shikimic acid, (ii) acidhydroxy proline, (iii) santonine, (iv) dianhydro-D-Glucitol, (v) hydroxy pipecolinic acid, (vi) andrographolide, (vii) piperazine-2-carboxylic acid, and (viii) cytosine);
  • A wide-range of biologically- and pharmacologically-active (some are FDA-approved drugs) compounds with an impact on specific molecular targets, cell signaling pathways and/or biological processes (TOCRIS Bioscience (n=1296), LOPAC (SIGMA, n=1280), Spectrum (MicroSource, n=2000), and Biomol (n=360) collections;
  • Prestwick Chemical collection (n=1120), mostly composed (85%) of off-patent, FDA-approved drugs;
  • NIHcollection (n=727), small molecules with a history of use in human clinical trials;
  • 480 protein kinase inhibitors;
  • 160 morphogens (namely, small molecules with a direct impact on cellular processes).

siRNA libraries

  • Dharmacon Reversioned siRNA SMARTpool Library, Whole Human siGENOME (~18,150 gene targets) Available in the following subset collections: GPCR, Druggable targets, Ubiquitin Conjugation, Ion Channels, Proteases, Kinases, Phosphatases, and epigenetics custom-mad collection;
  • Dharmacon siRNA SMARTpool Library, Whole Mouse siGENOME (~16,500 gene targets) Available in the following subset collections: Kinases, GPCR, Druggable targets;
  • Dharmacon Reversioned Deconvolved siRNA Library, Whole Human siGENOME composed of 4 siRNA unique sequences for each SMARTpool sample of the Whole Human Genome Library; ~72,600 samples;
  • Dharmacon Deconvolved siRNA Library Whole Mouse siGENOME composed of 4 siRNA unique sequences for each SMARTpool reagent in the Whole Mouse Genome Library; ~66,000 samples.

miRNA libraries

  • Dharmacon miRIDIAN™ microRNA Mimics (n=810) and Hairpin Inhibitors (n=810) (HUMAN);
  • Dharmacon miRIDIAN™ microRNA Mimics (n=642) and Hairpin Inhibitors (n=642) (MOUSE).

In addition, customized collections of any kind and format can be realiquotted for use in specific project upon a user's request or HTS personnel recommendation.


III. Lab Automation Setups

We can develop, validate and execute robotic methods that accommodate and fine-tune technical requirements and mechanical aspects necessary to precisely reproduce an experimental protocol previously validated at the benchtop level. During validation of the automation, manual steps are replaced systematically with instruments to ensure accuracy and robustness of the procedure. Once the sequence of events and the corresponding instrumentation are determined, a scheduling program is finalized and subsequently tested in a pilot experiment prior to final acceptance of technical and mechanical conditions (e.g. harshness of washing conditions, flow rates of dispensed liquid, mixing steps etc.).


IV. Data Management

We can assist users with data management, that is, the capture, storage and analysis of results. For screens performed in a sequential manner, screening parameters (variability of controls, variability of samples, dynamic range, hit rate) are monitored throughout the entire process to determine consistency of data and whether any screening run should be repeated. The approach for data normalization and hit selection may depend on several factors associated with type, format, duration etc. of any given assay, and the nature of the library used for the screen. Generally, a variety of methods (e.g. control-based, Z- or B-score) is assessed each time to find the most reliable and informative approach for subsequent data interpretation and hit finalization.



V. Cherry-picks, Confirmatory tests, and Dose-response curves

These are typical follow-up tests after a primary screen that we offer to users as a routine procedure aimed at the definition of a short-list of candidates for subsequent, more stringent validation strategies.


VI. Sample combination arrays

This is a procedure that may offer valuable information to better understand the molecular mechanisms that underlie a given phenotype (using combinations of bioactive molecules). Alternatively, it may be used to discover synergic effects of drugs. Sample arrays may be experimentally challenging due to a large variety of combinations that may arise when different concentrations and different dispensing times are tested. Through advanced robotic capabilities, we can however provide users with this experimental option.


VII. LUMIER

LUMIER (LUminescence-based Mamalian IntERactome) is a high-throughput automated platform developed in the Wrana lab for identification of novel protein-protein interactions in mammalian cells. In this assay, a Luciferase (LUC)-tagged fusion protein is co-transfected with a FLAG-tagged protein in mammalian cells. The interaction between the two proteins is determined by co-immunoprecipitating the FLAG-tagged protein and detecting the LUC-tagged interactor in the complex by its luciferase activity. LUMIER can easily identify transmembrane protein partners, dynamic interactions that are signaling- or isoform-dependent, as well as those that may occur only in the presence of post-translational modifications. The assay can be performed in 96 or 384-well format.


VIII. Next Generation Sequencing Analysis

The sequencing unit offers a broad range of applications using NGS with a focus on RNA-Seq technology. The services include library preparation from DNA, mRNA or total RNA. Samples are sequenced on either a HiSeq 3000 or NextSeq 500 sequencer. We offer free initial consultation to identify the best and cost-effective solution for your projects. We also provide bioinformatics support.