NCATS’ Stem Cell Translation Laboratory (SCTL) is seeking new collaborations to help achieve common goals in induced pluripotent stem cell (iPSC) biology in a faster and more coordinated fashion. Interested investigators may submit proposals on July 1, November 1 and March 1 to collaborate with SCTL throughout the year.
General Proposal Process
NCATS will assess submitted research proposals for scientific merit, technical feasibility, fit with available resources and alignment with SCTL programmatic goals. Steps include:
- Pre-proposal screening with SCTL staff to confirm eligibility as a collaborating entity and adequacy of the current data package. This process consists of submission of an abstract (no more than one page in 12-point Times New Roman) for the proposed project and a telephone discussion with SCTL staff. Send proposed project abstracts via email to Ilyas Singeç. View detailed proposal instructions (PDF - 160KB).
- An actionable existing data package. This means the applicant must:
- Prove that a protocol has already been tested using biological and technical replicates.
- Provide a complete list of reagents and other details.
- Submit a summary detailing the outcome of prior solid experimentation (e.g., a description of attempts to reproduce the protocol by different researchers in the same group or collaborators; information on optimization steps and troubleshooting carried out). View detailed proposal instructions (PDF - 160KB).
- Submission of a full proposal package. This includes a formal request (no more than five pages with data and figures, in 12-point Times New Roman) and specific supporting documents not to exceed two pages (e.g., publications, unpublished or preliminary data presented). Send proposal packages via email to Ilyas Singeç.
- Peer-reviewed, confidential scientific assessment of the submitted proposal by SCTL staff and advisory group members (composed of NIH staff with expertise in the proposal area). Decision-making criteria include:
- Strength of the data package
- Feasibility and the deliverables timeline
- Synergy with SCTL goals
- Translational sciences impact
- In-depth face-to-face meetings with potential collaborators and discussion of raw data under the protection of a confidential disclosure agreement.
- Agreement that all data (positive and negative results) and resources will be shared with the public.
Considerations for SCTL Collaborators
NCATS expects collaborative projects to have an emphasis on overcoming technological hurdles impeding the transition of iPSC research from “bench” to “bedside” (e.g., significant protocol improvement). These are not necessarily poor-quality protocols but rather those that are underdeveloped or have significant potential for improvement.
For example, a collaborator intends to use an iPSC line in preclinical studies but can obtain only 50 percent purity following differentiation, when purity greater than 95 percent is needed. Alternatively, a researcher obtains well-characterized cells of sufficient quality and purity, but they are prohibitively expensive and time-consuming. In this scenario, the collaboration would focus on replacing expensive reagents with more defined and economic small molecule compounds, as well as shortening the duration of the cell differentiation protocol. In all cases, measurable parameters (deliverables, timelines and resources) would be agreed upon and implemented as a metric for informed decision making.
Projects on protocol improvement and other technological hurdles will be initiated as soon as the review process is successfully completed. The SCTL team will conduct experiments to address the protocol improvement as defined in the research plan and will update collaborators on the progress made. NCATS SCTL staff will hold regular conference calls and in-person meetings for scientific exchange and progress evaluation. SCTL team members will rigorously test all steps of final protocols, including the use of biological and technical replicates; such testing will include repeat execution of the protocol by the same scientist, as well as execution of the protocol by a second team member to demonstrate transferability. NCATS will share final results via joint scientific publications, and complete protocol details will be included in a report on rigor and reproducibility testing accessible on the SCTL website. Additionally, the SCTL team will provide complete information on small molecule reagents to replace expensive recombinant proteins, xenogeneic material and undefined media components in cell differentiation protocols.
A project will be deemed successful when the corresponding protocol improved by the SCTL team achieves the agreed-upon common goal(s). Upon completion, NCATS will disseminate all relevant data, protocol steps and newly discovered reagents as detailed in the above section.
NCATS will terminate a project if it fails to meet the protocol improvement goals set by the research plan and if the SCTL team has failed to make progress despite repeated attempts at optimization. Examples of failures to improve the protocol include but are not limited to:
- Failure to improve the desired-lineage cell type yield beyond the initial level;
- Failure of high-throughput screens to produce small molecules that improve yield or the duration of differentiation steps or to replace the key expensive reagent; and
- Failure to decrease variability in protocol performance.
If project is terminated due to lack of significant protocol improvement, the joint team will make an effort to publish the negative results in order to inform the public on the roadblocks associated with the particular protocol.