Accelerating the Integration and Translation of Technologies to Characterize Biological Processes at the Single Cell Level (R01)

Accelerating the Integration and Translation of Technologies to Characterize Biological Processes at the Single Cell Level (R01) is sponsored by NIH Common Fund. This R01 (Research Project Grant) aims to accelerate the translation of technologies with preliminary data that offer significant advantages to clinical and biomedical researchers.

Expired RFA-RM-11-015: Accelerating the Integration and Translation of Technologies to Characterize Biological Processes at the Single Cell Level (R01) This notice has expired. Check the NIH Guide for active opportunities and notices. Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Office of Strategic Coordination ( Common Fund ) Components of Participating This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative ( http://commonfund. nih. gov/ ) through the NIH Office of the NIH Director, Office of Strategic Coordination ( http://dpcpsi.

nih. gov/osc/ ). The FOA will be administered by the National Institute of Biomedical Imaging and Bioengineering (NIBIB/NIH), ( http://www.

nibib. nih. gov ) Funding Opportunity Title Accelerating the Integration and Translation of Technologies to Characterize Biological Processes at the Single Cell Level (R01) R01 Research Project Grant Funding Opportunity Announcement (FOA) Number U01 RFA-RM-11-013 ; R21 RFA-RM-11-014 Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) This NIH Funding Opportunity Announcement (FOA), supported by funds from the NIH Common Fund, invites applications for R01 awards that will accelerate the translation of promising technologies for single cell analysis from prototype into practice, by taking them through the downstream development and validation process and establishing them as robust, well-characterized tools ready to transform our understanding of cell-level heterogeneity in a wide variety of clinical and research settings.

Awards will focus on supporting multidisciplinary teams that apply an integrative, quantitative approach to developing these technologies so they fulfill a critical unmet need by offering compelling advantages to end-users, but can be applied to multiple types of cell populations.

It is expected that applications will have well-defined goal(s) with intermediate quantitative Open Date (Earliest Submission Date) Letter of Intent Due Date January 23, 2012, by 5:00 PM local time of applicant AIDS Application Due Date(s) Required Application Instructions It is critical that applicants follow the instructions in 424 (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV . When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review. Part 1. Overview Information Part 2.

Full Text of the Announcement Section I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information I.

Funding Opportunity Description The goal of this FOA is to accelerate the translation of promising technologies for single cell analysis from prototype into practice, by taking them through the downstream development and validation process and establishing them as robust, well-characterized tools ready to transform our understanding of cell-level heterogeneity in a wide variety of clinical and The purpose of this FOA is to solicit applications that propose to validate and translate innovative technologies which have been demonstrated to have the potential to provide comprehensive analyses of individual cells within an in situ population.

The projects will be designed to fulfill a defined critical unmet need of researchers by providing, for example: 1) a groundbreaking clinical diagnostic device; 2) significantly higher sensitivity and specificity over existing approaches for detecting rare events, rare cells and for handling dilute or small volume samples; 3) order of magnitude improvements in the operating parameters, analysis and usability of existing approaches to establish them as methods of choice; 4) and/or innovative adaptation of techniques used exclusively with fixed cells or cell culture to analysis of live cells in situ.

This initiative is part of the Single Cell Analysis Program (SCAP) and is funded through the NIH Common Fund (See http://nihroadmap. nih. gov/ ), which supports cross-cutting programs that are expected to have exceptionally high impact.

Common Fund initiatives address key roadblocks in biomedical research that impede basic scientific discovery and its translation into improved human health. In addition, these programs capitalize on emerging opportunities to catalyze progress across multiple biomedical fields.

Single cell analysis has recently emerged as an important field of research because technologies have improved in sensitivity and throughput sufficiently to begin measuring and understanding heterogeneity in complex biological systems and correlating it with changes in biological function and disease processes.

By profiling individual cells it is possible to resolve rare cells, transient cell states, and the influence of organization and environment on such cells and states, which cannot be described by ensemble measurements.

The long-term goal of the SCAP is to accelerate this move towards personalizing health to the cellular level by understanding the link between cell heterogeneity, tissue function and emergence of disease through the discovery, development and translation of innovative approaches which will dramatically change the way cells are characterized.

The SCAP will focus on supporting work which will systematically measure, analyze and model cell-to-cell variation, and identify crucial differences and rare biological states, which may have important functional consequences. To robustly and systematically describe cell level heterogeneity, projects are expected to take a multiplexed approach with minimal perturbation, which can be applied reproducibly to any complex tissue.

Technologies and methods must also be capable of capturing spatiotemporal information to understand the organization, evolution and response of cell states as part of a functional population.

In addition, the SCAP emphasizes the application of these technologies to in situ populations of cells from multicellular organisms to link cell state measurements with complex, functional tissues which can inform our understanding of disease processes.

The SCAP has been designed as a five-year program with several components: (1) the collection, analysis and sharing of comprehensive expression datasets to understand the role of heterogeneity in tissues and systemically and identify critical parameters and states; (2) the discovery of new, innovative tools for spatiotemporal imaging, manipulation, analysis and modeling of a biologically relevant population of cells with minimal perturbation; (3) milestone-driven validation and translation of technologies for characterizing single cells in situ meeting the needs of end-users; and (4) development and coordination of a multidisciplinary research community through workshops and other collective endeavors.

Further details can be found on the Program’s website ( http://commonfund. nih. gov/singlecell/ ).

To accelerate the translation of promising technologies from prototype into practice, a key objective is to improve upon basic technical innovations that have already been demonstrated in principle and which have the potential to be robust, well-characterized technological solutions to the analyses of single cells in situ.

Preliminary results should indicate that the proposed solution would offer significant advantages to at least one group of end-users. The proposed project is expected to overcome barriers to in situ measurement of human or animal cells and adoption of the technique into routine use.

Investigators are asked to quantify the expected in situ performance measures and to benchmark them against current state-of-the-art approaches when describing these significant advantages. Validation of expected performance must be demonstrated using sufficiently large, functional, in situ populations of human or model animal cells.

Another key objective of this FOA is to support multidisciplinary teams who will develop innovative solutions to address critical unmet needs of clinical and scientific users. These teams must bring together the necessary biological, clinical, physical, computational, and engineering expertise with end-users and the necessary resources to realize the milestones which will guide the project.

An application may involve strategic partnerships with companies or other organizations to assess user needs, for validation or for dissemination. As part of clear leadership and project plans, each partner is expected to provide substantive contributions to intellectual or technical aspects of the project that are clearly differentiated from simple contractual arrangements.

It is recognized that the maximum project period supported by this FOA may not be sufficient for complete translation of some solutions, and in this case investigators are asked to briefly project their chosen milestones in a framework of larger milestones towards the final goal of their work.

Milestones should describe projected specific, measureable and achievable progress throughout the project period which can be used as an indicator of success towards an end-goal such as entry into clinical testing or product launch. A third key objective of this FOA is to enable the comprehensive analysis of cell state by clinicians and/or researchers.

Technologies should collect a sufficient number of autonomous parameters in parallel to uniquely describe multiple cell states and tissue-level functions with minimal perturbation and with high spatiotemporal accuracy and specificity.

Technologies should also be broadly applicable to other populations of cells and projects may include development or adaptation of appropriate data analysis techniques where appropriate for use by multiple end-users.

Investigators are expected to submit appropriate resource sharing plans, and should describe in detail how resources and data generated under the grant would be shared and how technologies would be disseminated, consistent with achieving the goals of the program. The annual SCAP workshop will be also used to build synergy.

To meet these key objectives, investigators must justify the unmet need which the technology fulfills, give details of the major tasks in further developing, validating and translating this technology. They must also describe sufficient proof of principle data to justify further developing this technology towards a realistic end-goal. Detailed instructions are described in Section IV.

6. Other Submission Requirements. Applications which focus on the validation and translation of technologies which have recently been demonstrated in principle with single cell organisms or in vitro and have the potential to transform our understanding of heterogeneity and the link with tissue-level function are encouraged.

In addition, integrated and automated solutions for multiplexed analysis of autonomous cell characteristics and components with the potential to improve performance by an order of magnitude are encouraged. Applications to develop technologies and analytical methods for classes of cellular components which have not yet been measured at the single cell level are also encouraged.

Applications which seek to establish proof-of-concept are encouraged to respond to a companion FOA RFA-RM-11-014 and those seeking to primarily use transcriptional analysis to respond to another companion FOA RFA-RM-11-013 .

Applications focused on improvements of current technologies which will not lead to a foundational change in the methods employed by end-users, are focused on in vitro analysis or which are validated using single cell organisms will be Examples of technology translation supported by this FOA may include (but are not limited to): Automated system for the characterization of human pathology specimens with imaging and targeted -omic analysis Development of a groundbreaking diagnostic tool which enables early detection of disease states and informs prognosis and treatment through an understanding of the heterogeneity of the states present A device which integrates detection and analysis of transient or rare cell states in dilute or small volume clinical samples A system for the long-term monitoring of heterogeneous or differentiating cell populations for comprehensive analysis of environmental and autonomous factors regulating cell states and measuring response to transient and complex perturbations In situ analysis of cell heterogeneity and comprehensive cell state measurements that can support development of prognostic models of individual cell fate and population disease progression A tool for measuring and manipulating individual cell states within a heterogeneous or differentiating cell population, resulting in a desired change of tissue-level function A system with high spatiotemporal resolution and throughput for characterizing the comprehensive response of individual cells within a heterogeneous population to challenges such as infectious agents for the development of prophylactic and therapeutic treatments Application Types Allowed Glossary and the SF 424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

NIH intends to fund an estimated 3-5 awards. The total amount of funds available for these awards is approximately $4,000,000 in FY 2012. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.

Applications are limited to a maximum of $750,000 annual direct costs. The scope of the proposed project should determine the project period. The maximum period is 5 years.

Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education: Hispanic-serving Institutions Historically Black Colleges and Universities (HBCUs) Tribally Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government - NIH Intramural U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement, are allowed. Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s)) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support.

Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Each PD(s)/PI(s) is expected to devote a minimum of 3.

0 person months (25% effort) to the project.. This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. IV.

Application and Submission Information 1. Requesting an Application Package Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants. gov .

Form of Application Submission It is critical that applicants follow the instructions in (R&R) Application Guide , except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and By the date listed in Part 1.

Overview Information , prospective applicants are very strongly encouraged to submit a letter of intent that includes the following information: Descriptive title of proposed research Name, address, and telephone number of the PD(s)/PI(s) Names of other key personnel Participating institutions Number and title of this funding opportunity The letter of intent should be sent to: Division of Applied Science and Technology National Institute of Biomedical Imaging and Democracy Plaza II, Suite 200 Required and Optional Components The forms package associated with this FOA includes all applicable components, mandatory and optional.

Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional All page limitations described in the SF424 Application Page Limits must be followed.

PHS 398 Research Plan Component All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the SF424 (R&R) Application Guide, with the following modification: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. Foreign (non-US) institutions must follow policies described Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times Part I. Overview Information contains information about Key Dates.

Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission. Organizations must submit applications via Grants. gov , the online portal to find and apply for grants across all Federal agencies.

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide. 4.

Intergovernmental Review (E. O. 12372) This initiative is not subject to intergovernmental All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .

Pre-award costs are allowable only as described in the NIH Grants Policy Statement . 6. Other Submission Requirements and Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide.

Paper applications will not be accepted. Applicants must complete all required registrations before the application due date. Section III.

Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically . All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package .

Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR).

Additional information may be found in the SF424 (R&R) Application Guide. tips for avoiding common errors. Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations , NIH.

Applications that are incomplete and/or nonresponsive will not be Applications Involving the NIH Intramural Research The requests by NIH intramural scientists will be limited to the incremental costs required for participation.

As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).

These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. If selected, appropriate funding will be provided by the NIH Intramural Program.

NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA.

Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application.

The intramural scientist may submit a separate request for intramural funding as described above. The following exceptions to the general R01 instructions Health Relevance Statement : Investigators should clearly articulate how addressing the needs of end-users through the validation and translation of technology will improve public health.

The statement should highlight how understanding will be transformed and the size and nature of the PD(s)/PI(s) should cite relevant details that illustrate their ability to validate and translate technologies and lead multidisciplinary teams. In their personal statements, investigators are asked to briefly summarize achievements in both single cell analysis and goal-directed, needs-driven research.

PD(s)/PI(s) should include attendance at the annual workshop as part of their Strategy : The 12 page research strategy should clearly address: The Challenge: What technology is needed and why? How have these needs been assessed and who beyond the users will benefit? What are the barriers to validation and translation?

Impact: Why will this technology transform the field of single cell analysis and our understanding of heterogeneity? How does the proposed research match the stated goals of the NIH Common Fund, in particular supporting cross-cutting research? What are the measures of a successful project?

How will translation of this technology result in a change in the methods and standard procedures currently used in single cell analysis? Approach: How does the proposed work differ from other approaches? What factors have been taken into consideration to maximize the likelihood of success?

What is the expected quantitative performance of the technology when analyzing in situ cells and how does this compare to other approaches? How will technologies be translated and disseminated to broaden and Timeline: What are the key milestones in the development, validation and translation of the proposed technology? How will progress be evaluated?

How will risk be managed? Plan : A one page description of the leadership plan, describing the structure, budget allocation and responsibilities of each component of the team, communication plans, intellectual property management and processes for resolving conflicts and scientific direction should be included as an attachment entitled Leadership Plan under Other Project Information Component.

Multiple PD(s)/PI(s) applications should address these same elements as part of their Multiple PD(s)/PI(s) Leadership Plan. Each PD/PI is expected to devote a minimum of 3. 0 person months (25% effort) to the project.

Sharing Plan : To accelerate the field of single cell analysis, grantees are expected to participate actively and openly in annual workshops. In addition to attending the annual workshop, investigators should describe how information will be rapidly disseminated and unique resources shared to advance biomedical research, consistent with achieving the goals of the program.

Details of the kinds of resources to be developed including data, model organisms and genome-wide association studies, what format these resources would be disseminated in and how they would be shared should be included in the plan. The plan should also include plans for sharing raw (unreduced) data with other researchers who may wish to analyze it independently.

Substantial information sharing is critical to the overall program, though it is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the scientific discovery or there may be other cases in which protection of human subjects need to be abided by .

Investigators are expected to be aware of and abide by all applicable NIH guidance for sharing of research resources and data, consistent with existing laws, regulations, and policies. Please see: http://grants. nih.

gov/grants/policy/data_sharing/data_sharing_faqs. htm. The adequacy of resource sharing plans will be considered by program staff of the funding organization when making recommendations about funding applications.

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115 . V. Application Review Information Only the review criteria described below will be considered in the review process.

As part of the NIH mission , all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer For this announcement, note the following: Reviewers should note that this FOA focuses on tool validation and translation and so should expect sufficient proof-of-principle data to assess whether the proposed quantitative milestones are reasonable.

Furthermore, the reviewers should understand and accept that later milestones may extend beyond the project period. Therefore, reviewers should balance the significance and innovation afforded by the long-term goal with the feasibility and approach of the milestones proposed within the project period.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Will the project establish transformative new capabilities for the analysis of single cells and single cell heterogeneity in populations of human or model animal cells?

Will the technology address critical unmet needs and significantly advance the utilization of single-cell methods in clinical practice, and/or address currently intractable scientific questions about cell Does the application address barriers to single cell analysis in situ or in vivo that are due to a scarcity of tools to identify, characterize, Will the project generate foundational resources (e.g. tools, methods) that will be widely used throughout the basic and translational Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project?

If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?

If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the investigators have appropriate experience with validating and translating biomedical technologies and with assessing and meeting user Will the leadership plan optimize the management of a milestone-driven, multidisciplinary project?

Is it clear, appropriate and Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?

Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the application represent an innovative technological solution which overcomes current scientific or technical barriers? Will the technology from the project result in new knowledge or capabilities for end-users?

What is the potential for this technology to be widely adopted by the community as the analytical method of choice, result in previous approaches becoming obsolete or result in a groundbreaking change in understanding of Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented?

If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

How will the technology be made sufficiently selective, sensitive or appropriate for the intended use in analyzing single cells as part of a functional population in situ?

How will the approach lead to a rigorous distinction between potentially subtle cell subtypes, developmental stages and/or functional Does the approach integrate and make full use of the skills of Is the timetable of milestones adequate, feasible and Has proof of principle been established for the technology with quantitative specifications of expected performance for analyzing cells in Is the validation of the technology adequate and appropriate and will it reduce the