Conrad Prebys Center for Chemical Genomics

HTS for Drug Discovery Catalyst Grant Application

Notice: Working with the Conrad Prebys Center for Chemical Genomics (CPCCG), the CTRI has committed $25,000–$50,000 to "Catalyst Funding" for 5–10 high-throughput screening (HTS) assay development projects, thus encouraging early steps of translating breakthrough discoveries in the laboratory towards clinical applications.

About the Conrad Prebys Center for Chemical Genomics

The Conrad Prebys Center for Chemical Genomics (CPCCG), located at the Sanford-Burnham Medical Research Institute (SBMRI) in La Jolla, provides conversion of an investigator's prototype assays into robust, scalable and automatable high-throughput screening assays and generation of pilot screening data from small test libraries.

The CPCCG screens chemical compounds to find the few that could potentially be developed into new medicines. All of the results from the CPCCG's activities are placed into a public database called PubChem, made available to all researchers, in both the public and private sector, for their use in studying biology and disease. Partnering to translate basic research into preclinical drug leads, they provide a comprehensive suite of capabilities for preclinical small molecule drug discovery, complete with experienced project management to ensure efficient execution of milestones. The Prebys Center partners with investigators at Sanford-Burnham as well as external parties including those from industry and private foundations and universities.

Over the past seven years, CPCCG has assembled unique drug discovery capabilities, impressive laboratory robotics infrastructure, veteran pharmaceutical talent, and experience in attracting and executing successful academic-industry partnerships. CPCCG is one of four Comprehensive Centers of the NIH's Molecular Libraries Probe Production Centers Network (MLPCN), as well as being designated as one of five Comprehensive Centers of NCI Chemical Biology Consortium (CBC). Through the MLPCN, CPCCG has had over four years' experience attracting and mentoring collaborators, and co-applying for competitive NIH FOAs (R03, R21, R01, R33, SBIR) as well as managing over 25 projects per year with multiple PIs from many institutions. Participation in NIH Steering committees has afforded access and knowledge of additional funding opportunities and programs targeted toward rare and neglected diseases (TRND), and translational research (CAN, NCATS). Additionally, through the CBC, CPCCG has extensive experience and success in an aggressive, deliverable-driven contract research environment, and intimate knowledge of the NIH's NeXT program. Please visit the lab's webpag for more information.

High-Throughput Screening Catalyst Grants

Description

The goal of this catalyst funding is assist UCSD CTRI investigators in fulfilling the multiple technical requirements leading to successful application for two new NIH Funding Opportunity Announcements (FOAs) for using developed high-throughput assays to interrogate large chemical collections of small molecules for the purposes of finding validated hits against translational targets or pathways related to human diseases [http://grants.nih.gov/grants/guide/pa-files/PAR-12-058.html; http://grants.nih.gov/grants/guide/pa-files/PAR-12-059.html]. Both of these FOAs expire on September 8, 2014.

If awarded, this Catalyst Grant has two phases:

Phase I

Investigators collaborate with the HTS Assay Development Core in the CPCCG to review assay concepts, know-how, reagents, and protocols for the investigators' prototype assay. They will then develop a practical assay concept and work plan to generate the required reagents, and deliver a workable prototype HTS assay of at least 384 wells. The professionals in the CPCCG HTS Assay Development or HCS Cores may further miniaturize and optimize to a 1536-well format, then generate pilot HTS data in this final format. The data generated by the Core includes confirmation of automated assay robustness (Z'>0.5, S/B >4, CV<10%) and pilot screening of a small (~2K compounds) library to establish the approximate hit rate for the primary assay. Furthermore, CPCCG will assist the PI in developing a plan for a cascade of follow-up assays (orthogonal, counter screen, selectivity), to demonstrate that these assays can support quantitative dose-response studies, and where possible generate actual data on pilot hits through this cascade.

Phase II

Preparation and submission of the NIH R01 or R21 grant application. Using the HTS data generated by the Core, the PI prepares the background and research plan of the grant application. The CPCCG will co-apply and assist in drafting the specific aims, screening cascade, and timelines, and provide a subcontract budget. The application is accompanied by a letter of support (LOS) from Dr. Thomas "T.C." Chung, Project Manager for the NIH Roadmap program at CPCCG and/or Dr. Michael R. Jackson, VP Drug Discovery and Development at CPCCG. Dr. Chung is available as a resource to help guide PIs in preparing the R01 or R21.

How to Apply

An application may be submitted at any time using the "Application for Funding" button on the CTRI TRT website. Proposals will be reviewed by an HTS Assay Advisory Board composed of CTRI and CPCCG leadership. It is highly recommended that prior to submission of an application, PIs should establish dialog with Dr. Thomas "T.C." Chung, Director of Outreach and Project Manager (tchung@sanfordburnham.org) who will review your project, explore various options for assay design, and agree on the most suitable assay format with the appropriate HTS Assay Development or High Content Screening (HCS) Core Directors.

  • Principal investigators for these awards must be members of the CTRI. To join, please click here
  • Principal investigators must be full-time faculty members at UCSD
  • Provide a 1-2 page proposal that describes:
         The biology of the project
         The proposed assay format
         The development plan with a timeline (including any resources required from CPCCG)
         The relevance and novelty of the target/assay to drug discovery
         The reasons why an HTS screen using the assay proposed is likely to be funded by the NIH
  • NIH formatted biosketch
Review Criteria

1. Novelty of the assay – assays proposed must be "de novo" assays – i.e., where new reagents need to be generated to generate feasibility data. (Slight reconfigurations of existing assays or commercially available assays will not be funded).

2. Relevance to drug discovery – the target of the assay should ideally be implicated in a disease or disease process and thus have a plausible clinical application.

3. Probability that the HTS assays meet the criteria for funding by NIH Special Emphasis Panel for PAR-12-058 (R01) or PAR 12-059 (R21) Grant Applications – the proposed final HTS assay should fit the criteria outlined by the respective FOAs. Preference will be given to those applicants that are at a more robust level of technical readiness. Applicants agree to lead an R01/R21 application and agree to work with the CPCCG team to generate the preliminary HTS data required for submission.

For inquiries and further information, please send an email to ctri-lab@ucsd.edu