Vanderbilt University
Vanderbilt Institute of Chemical Biology
High Throughput Screening Facility

Services

The Vanderbilt HTS Facility provides a variety of services to the research community. Consultations are available for assay design, optimization, development, and validation, as well as integrating automated HTS and data analysis.

The compound collection can be accessed independently of screening, and HTS compatible supplies for testing and validation are available. Training services are also provided to allow for walk-up use of state-of-the-art instruments. To contact HTS staff to discuss specific needs, please complete the Intake Form. Staff will evaluate requests and provide information describing the suggested resources required.


Train independent users Screen compounds Compound distribution

 

Forms

Intake Form
Use this form to request a quote for service, request a consultation, inquire about assay development, or transfer an assay for HTS.

Intake Form - update
This form is to be used only by those HTS customers who have already completed an intake form and need to update their financial information and assay specifics.

 

NEW Account or Training Form
Use this form to submit information to request instrument training for a walk-up user, add additional investigators to a project.

 

Center Number Update Form
Please update center numbers with this form.

Assay Design and Validation

Through the advanced, HTS-compatible instruments, the HTS facility supports a wide variety of detection modalities for assay measurements including: absorbance, fluorescence, time-resolved fluorescence, fluorescence polarization, fluorescence resonance energy transfer (FRET), time-resolved FRET, luminescence, bioluminescence resonance energy transfer (BRET) and scintillation proximity assays (SPA). Cell-based and cell-free assays in experimental systems that have been used in prior models have included but are not limited to; recombinant proteins, membrane fractions, cellular isolates, cell lysates, cell lines, and whole model organisms (e.g., zebrafish, C. elegans, and yeast).

The HTS facility is proficient at helping research investigators develop HTS-compatible assays, obtain preliminary data for grants and funding opportunities, and to screen for the identification and investigation of new compounds for basic research and pharmacological discovery. Discoveries include novel modulators of G-protein coupled receptors, ion channels, transporters, proteases, oxido-reductases, cellular adhesion proteins, lipases, growth factor receptors, proto-oncogenes, protein-protein interactions, DNA-protein interactions, and other molecular targets and pathways that are important in numerous diseases such as neurodegenerative diseases, cardiovascular diseases, malaria, bacterial and viral diseases/illnesses, diabetes, cancer, and HIV.

Assay Targets:

  • GPCR Modulators
  • Ion Channel Modulators
  • Cardiovascular Zebrafish Models
  • Diabetes Targets
  • Anti-Malarial Targets
  • Foodborne Illness Targets
  • Coagulation Inhibitors
  • Transcriptional Modulators
  • COX Inhibitors
  • Choline Transporters
  • Obesity and Cachexia Regulation Target
  • Colon Cancer Targets
  • Pancreatic Cancer Targets
  • Lung Cancer Targets
  • Breast Cancer Targets

A project begins with completion of an Intake Form. Once received, a HTS staff will schedule a consultation to discuss the adaptation and implementation of the assay to the HTS facility. Typically, assays are validated manually by individual laboratories and evaluated to determine the level of automation and instrumentation needed for HTS services. Once the assay is validated with positive and negative controls and the robustness of the assay (Z-factor/Z’) is determined the assay is ready to be automated. During validation of the automation, manual steps are replaced systematically with instruments to ensure accuracy and precision/fidelity of the assay as observed in the manual process.  For example, manual pipetting into a 384-well plate can be replaced with use of a Thermo Multidrop, which dispenses liquid into an entire plate evenly and accurately in seconds. Another example is the Velocity11 Bravo liquid handler, this device can aspirate liquid from an entire plate, wash it, and add a solution to a plate very precisely in a matter of minutes. After determining the sequence of events and instrumentation for the assay, a robotic sequence called a schedule is created to integrate these assay procedures into an automated fashion.

Software determines the amount of time each sample will take during individual movements of the robot and the composite time for all samples to be assayed. Testing of the schedule begins with running the schedules for individual instruments, followed by testing of all instruments without reagents, and finally, testing of all instruments with water. Next, an experiment is run using all instruments and robotics integrated by the schedule with experimental controls. After the biological procedure and the instrumentation are validated, the assay is ready for compound screening. The growing library available for screening includes over 160,000 compounds.

A large number of data can be generated by HTS and our specialized HTS informatics staff can assist with custom-made software to help assimilate, analyze and reduce data to appropriate specifications for hit picking, follow-up analyses, and hit validation.

 

Policies

Lab Policy

Administrative Policy

Safety and Emergency Policy

DATA SHARING Policy

Authorship guidelines

Compound Screening

  Target Identification and Validation   Assay Development   High-Throughput Screening   Lead Identification   Preclinical Development
• DMPK
• ADMET
  Clinical Development  
 

Assay Design
How do we measure our target?
Weeks – months

 

Screening
Can we do HT screening?
Weeks – months

 

Potency and efficacy
Does it work how we want it to?
Days – weeks

 
 

Validation
Does it work?
Weeks – months

 

Confirmation
Can we repeat results?
Days – weeks

 

Selectivity
How specific is it for our target?
Days – weeks

 
 

Pilot Library Screen
Can we detect "hits"?
Days – weeks

 

Chemistry Optimization

 

Compound Distribution

The compound collection at the HTS facility is comprised of several commercial and private sources. Depending on the research investigator’s interest subsets or the entire collection can be requested for testing using an online compound distribution request which allows plate type, volume, and concentration to be tailored to the investigator’s needs. The HTS strives to continually enrich the library with novel scaffolds and actively encourages investigators to deposit compounds into the library for distribution and screening. Synthetic and natural product chemists are also encouraged to contact the facility about deposition opportunities.

 

Library # of Compounds Composition
Vanderbilt Discovery Collection 100,000 Selected from Life Chemicals collection for HTS. The compounds in this collection were chosen by Vanderbilt medicinal and computational chemists to provide lead-like motifs, minimum pan-assay interference, and maximum diversity.
Chembridge/ChemDiv
(VICB Collection)
160,000 Drug-like, diverse set of small molecules.
Molecular Libraries Small Molecule Repository (MLSMR)* 150,000 Remaining compounds from MLSCN (limited volumes left).
Spectrum Collection 2,000 A wide range of biologically active and structurally diverse compounds. 50% drug components, 30% natural products, 20% other bioactive components.
NIH Clinical Collection I and II 730 Small molecules that have history of use in human clinical trials.
NCI Purified Natural Products 816 The NCI’s Chemical Biology Consortium (CBC) A focused natural product collection from the NCI's Chemical Biology Consortium (CBC) consisting of 816 pure compounds acquired from ANALYTICAL and MerLion. Access based on approval of project focus (oncology-related projects are prioritized).
Cayman Lipid Library 1,000 Broad variety of bioactive lipids.
Fesik Fragment Library 16,000 Diverse collection of fragment molecules from 8 vendors, rule of 3 compliant, and filtered against non-specific and interfering molecules.
Marnett Collection 900 NSAID derivatives that contain cyclooxygenase inhibitors, PPARgamma activators and apoptosis inducers.
Roche Published Protein Kinase Inhibitor Library** 235 Small molecule protein kinase inhibitors disclosed in peer-reviewed scientific publications.
Ion Channel >6000 A collection from Life Chemicals targeted to ion channels compiled using 2D fingerprint similarity methodology.
Epigenetics Collection 51 A group of small molecule modulators with biological activity for use in epigenetic research.
Enzo Kinase Inhibitor Library 80 The Screen-Well™ Kinase Inhibitor Library contains 80 known kinase inhibitors of well-defined activity. Includes inhibitors of these important kinases: Insulin/IGF Receptors, PI 3-Kinase, CaM Kinase II, JAK, PKA, CDK, JNK, PKC, CKI II, MAPK, RAF, EGFR, MEK, SAPK, GSK, MLCK, Src-family, IKK, PDGFR, VEGFR, and many more.
GSK Published Kinase Inhibitor Library*** 349 A set of 349 small molecule kinase inhibitors spanning over 30 chemotypes that have been previously published by GlaxoSmithKline in peer-reviewed scientific journals.

* Requires PubChem data deposition
** In collaboration with Roche Pharmaceuticals
*** In collaboration with GlaxoSmithKline

 

Compound Libraries

Bio-active Lipid Screening Library

NIH Clinical Collection I

NIH Clinical Collection II

Spectrum Collection

 

Training and Walk-up Instrument Use

Most of the HTS instruments are available for walk-up use. Instruments can be reserved online for as little as 15 minutes at a time, and instruments can be accessed 24 hours a day, seven days a week. A short training for every HTS instrument and automation is required for use and for reserving instrument time. Training includes understanding the capabilities of the instrument, the limitations, instrument functions and safety, data capture, analysis, access, and storage, as well as HTS facility policies and procedures for instrument access and use. Training time will be charged to the investigator’s account and generally lasts between 30-60 minutes, depending on the equipment being used. Following training access to the HTS facility and instrument reservation and usage will be granted. Our instruments can be found here.

   

Grant Writing Information

The HTS staff can help research investigators with HTS related grant writing and funding opportunities. The HTS staff will be happy to provide budget quotes, facility descriptions, and letters of recommendation and support. All new users need to complete the Intake Form for assistance with grants. If you are a current user or have questions, please contact Paige Vinson via email or call (615) 322-0342 for further information.

   

Funding Information

Listed below are several resources with information for funding HTS projects.

   

 

 


 

Vanderbilt University School of Medicine | Vanderbilt University Medical Center | Vanderbilt University | Eskind Biomedical Library

Vanderbilt High-Throughput Screening Facility Robinson Research Building, Room 824, 2200 Pierce Avenue, Nashville, TN 37232 (615) 936-7098 hts@vanderbilt.edu
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