Elucidation and Validation of the role of Transporters in the Placenta, Lactating Mammary Gland, Developing Gut, and Blood Brain Barrier (UC2 Clinical Trial Not Allowed)

Elucidation and Validation of the role of Transporters in the Placenta, Lactating Mammary Gland, Developing Gut, and Blood Brain Barrier (UC2 Clinical Trial Not Allowed) is sponsored by National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH). This funding opportunity invites applications to form Transporter Elucidation Centers (TECs) to understand the functional transport of nutrients and drugs to the developing fetus and infant through a focus on human placenta, lactating mammary gland, and developing gut.

Expired RFA-HD-23-003: Elucidation and Validation of the role of Transporters in the Placenta, Lactating Mammary Gland, Developing Gut, and Blood Brain Barrier (UC2 Clinical Trial Not Allowed) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute on Drug Abuse ( NIDA ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Dietary Supplements ( ODS ) Office of Nutrition Research ( ONR ) Funding Opportunity Title Elucidation and Validation of the role of Transporters in the Placenta, Lactating Mammary Gland, Developing Gut, and Blood Brain Barrier (UC2 Clinical Trial Not Allowed) UC2 High Impact Research and Research Infrastructure Cooperative Agreement Programs NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022 Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity See Section III.

3. Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose This Funding Opportunity Announcement invites applications to form Transporter Elucidation Centers (TECs) as part of a Transporter Elucidation Network (TEN).

TECs funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) will address key knowledge gaps in functional transport of nutrients and drugs to the developing fetus and infant through a focus on human placenta, lactating mammary gland, and developing gut. Such projects may necessitate deorphanization and characterization of understudied transporters and functional variants.

TECs funded by the National Institute of Drug Abuse (NIDA) will address knowledge gaps in the role of transporters in the blood brain barrier that transport substances and treatment agents relevant to NIDA.

TECs will work together to generate knowledge and resources that will be shared with the broader research community to advance our understanding of nutrient, drug, and dietary supplement constituent transport to the developing fetus and infant. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide , except where instructed to do otherwise (in this FOA or in a Notice from 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 Announcement Section I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Funding Opportunity Description The overarching goals of the Transporter Elucidation Network are to elucidate novel roles for transporter proteins (e.g., solute carrier (SLC) and ATP-binding cassette (ABC) families) and to validate existing and emerging models of their functional roles across and within the human organism.

The objective of awards made to this Funding Opportunity Announcement will be to improve our understanding of the functional transport of nutrients and drugs that are directly relevant to the developing fetus and infant. This will be accomplished via a focus on the human placenta, lactating mammary gland, developing gut, and/or blood brain barrier.

After a meal or oral drug or dietary supplement ingestion, the body uses transporters to take up and distribute nutrients, metabolites, xenobiotics, and/or drugs to cells and organelles. In the case of the developing fetus and newborn infant, the placenta and lactating mammary gland are essential organs for nutrient and drug transport.

Thus, the digestive tract (particularly during early development), placenta, and mammary gland form a key triad of organs responsible for nutrient and drug disposition during pregnancy and infancy. The blood brain barrier serves as a critical tissue for the developing fetal brain.

Given that transporter proteins are responsible for transmembrane conveyance of nutrients, metabolites, and drugs, individual variability in transporter variants and regulation, such as those for the sodium-dependent vitamin C transporters SLC23A1 and SLC23A2 , is likely to underlie individual variability in outcomes or measures in the infant observed in response to dietary or pharmacological interventions in the mother.

This highlights the importance of their understanding at the allelic level in realizing precision medicine and precision nutrition.

Despite the abundance of transporters in the genome and the key role that these transporters play in the uptake and disposition of ingested nutrients and minerals, dietary metabolites, xenobiotics, dietary supplement constituents(s), and pharmaceutical drugs across cell and organelle membranes, most of these genes are poorly characterized regarding solute specificity, organ and life stage-specific distribution and expression, and functional consequence of allelic and splice variants.

Transporters can exhibit specialized functions based on cellular, tissue, or developmental context such as high affinity-low capacity vs. high capacity-low affinity forms or fetal vs. adult forms. Subcellular localization of transporters, such as in the apical vs. basolateral membrane of enterocytes or localization in organellar membranes, also contributes to their functional diversity.

Additionally, the relative affinity of transporters for different solutes combined with different solute milieus in cells can mean that key transporters for a solute depend on cell and tissue context. Thus, the functional role of individual transporter proteins and transport of molecules can be complex.

The current heavy reliance on mRNA expression data and inference of function in developing tissue and organ models of transport highlights the need for a concerted and systematic effort to elucidate novel transporter function and validate functional models of transport to have an accurate understanding of nutrient and drug disposition in and across organs.

The necessity of fully understanding nutrient, drug, etc. transport therefore requires a two-fold approach of increasing our understanding of understudied individual transporter proteins, including their allelic variants, as well as elucidating their roles within particular organs, tissues, and cells with varying solute milieus.

Advances in modeling human tissues such as the use of organoids and micro-physiological systems and the ability to collect, sort, label, and study small numbers of ex vivo human cells can now be coupled with improved analytical techniques such as mass spectrometry for drug and nutrient fluxomics across membranes and single-cell omics technologies.

At the same time, advances in high throughput functional screening capabilities, high resolution cryo-electron microscopy, and bio- and chem-informatics approaches can be applied to elucidate basic properties of understudied transporter proteins. Foundational efforts on transporter proteins, such as that of the RESOLUTE Consortium ( https://re-solute. eu/ ), can be built upon.

There is also the need to foster and enhance a skilled and diverse scientific workforce with expertise in multiple aspects of understanding transporter protein function from biochemical properties through to dynamic flux of nutrients within and across organisms.

Objectives and Scope of the Centers Two important aspects of fully understanding the functional transport of nutrients, drugs, etc. within human cells and tissues are (A) having a detailed understanding of transporter genes and their expressed protein variants’ functions and ligands and (B) elucidating and validating the functional role of transporter proteins within specific tissues and cell types.

The first aspect can be enabled by recent advances in bio- and chem-informatics approaches, many of which are now powered by artificial intelligence approaches, coupled with an increased technical capacity for small molecule screening and molecular structural determination.

For the second aspect, ‘omics technologies that can be applied to ex vivo human tissues and engineered biomimetic organoid/chip systems provide new opportunities for resolving function and membrane localization of transporters in native biological contexts.

This FOA seeks to establish at least two Transporter Elucidation Centers that will work together in a Transporter Elucidation Network (TEN) in an integrated manner to increase our understanding of the understudied human solute carrier (SLC) and ATP-binding cassette (ABC) families of transporter proteins as well as how they function together and with other transporters in the placenta, lactating mammary gland, developing gut, and blood brain barrier to transport nutrients, dietary supplement constituents, and drugs.

Scientific Interest of th e Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) TECs supported by NICHD are intended to (1) functionally validate existing and emerging models of transport of nutrients and drugs within the placenta, lactating mammary gland, and developing gut and (2) elucidate novel roles for solute carrier (SLC) and ATP-binding cassette (ABC) families in these organs.

In scope are mechanistic studies addressing key developmental windows to elucidate the relationship between life stage-dependent expression and function of transporters and associated differences in xenobiotic and nutrient absorption and bioavailability (e.g., in infants vs. adolescents). Proposals may study transporter sequences and specimens from healthy individuals and/or those with known or putative transporter dysfunction.

Scientific Interest of National Institute of Drug Abuse (NIDA) TECs supported by NIDA are intended to increase our understanding of the expression, structure, and function of SLC and ABC transporters, particularly on the cell membrane and subcellular organelles of the blood brain barrier that play a role in the transport, disposition, and pharmacological and toxicological effects of opioids, psychostimulants, and other addictive substances and treatment agents of relevance to NIDA.

Scientific Interest of Office of Dietary Supplements (ODS) TECs supported by ODS are intended to increase the understanding of transport of dietary supplement constituents by SLC and ABC transporters. Scientific Interest of Office of Nutrition Research (ONR) TECs supported by ONR are intended to increase the bioinformatic understanding of SLC and ABC transporters of nutrients, metabolites, and xenobiotics.

This includes: (1) identifying solutes for transporters for which a solute has not been determined except through in silico assumptions based on structure; (2) broad screening of transporters to identify other competing solutes that may not have been previously elucidated (example of vitamin C being transported by “glucose transporters”); (3) determination of the clinical relevance of haplo-insufficiencies or common allelic variants in human transporters.

TEC applicants must propose either (A) functional transport studies in at least two of the following tissues - the human placenta, lactating mammary gland, developing gut, or blood brain barrier or (B) include an informatics/screening component for SLC and/or ABC transporters and functional transport studies in at least one of the following tissues - the human placenta, lactating mammary gland, developing gut, or blood brain barrier.

Examples of types of projects to be undertaken by a Transporter Elucidation Center include, but are not limited to: The use of mass spectrometric techniques to measure transporter protein and nutrient levels in various layers of the human placenta at different developmental stages; Use of cryo-EM to determine previously unobtainable transporter protein structures to facilitate computational docking models or assays; Deorphanizing transporters through coupling of computational and high throughput experimental approaches to uncover endogenous ligands and solutes; Proteomic and metabolomic characterization of cells isolated from human milk (i.e., liquid biopsies); Use of a wide range of biologically relevant small molecules labeled with stable isotopes to study relative transporter affinity and fluxomics; Fluxomic studies in human iPSC-derived gastrointestinal organoids at various stages of development.

Applications that are not responsive to this funding announcement: Projects listed below are not within the scope of this funding announcement. Applications proposing out of scope projects are not responsive to this FOA and will not be reviewed.

Applications focused on studying mRNA levels of transporters in cells and tissues; Applications that propose work in non-human animals or non-human tissues, cells, etc.; Applications that propose to study transporter proteins of non-human sequence origin; Applications that propose clinical trials; Proposals for Centers that do not propose to study at least two of the following tissues: the human placenta, lactating mammary gland, developing gut, and/or blood brain barrier, or study one of those tissues along with an informatics/screening approach for ABC and/or SLC transporters.

Components of the Tissue Elucidation Network Transporter Elucidation Network : The TEN will be made up of Transporter Elucidation Center awardees to this FOA, awardees to potential future related FOAs, the NIH TEN Working Group and other scientists and groups the Steering Committee agrees to include within the TEN. The Network structure is meant to enable the overall goals of the Transporter Elucidation program.

NIH TEN Working Group (WG): Consists of NIH programmatic staff from multiple Institutes, Centers, and Offices of the NIH. This group will be primarily responsible for the stewardship of the TEN and Transporter Elucidation program. Steering Committee (SC): The SC will provide coordination activities for the TEN.

The SC will include PDs/PIs of each of the awards and NIH TEN WG members. The SC will be chaired by a PD/PI that is nominated by the SC and approved by the NIH. The SC will establish subcommittees to oversee the development and implementation of Network policies including data release.

The number of NIH votes may not exceed one third of the total number of votes on the SC. The number of votes from a multiple PI award will be one. Votes will inform recommendations to the NIH.

Subject Matter Experts (SMEs): The NIH TEN WG will recruit outside experts (non-awardees) of relevance to the TEN to provide advice to NIH. The NIH TEN WG may solicit from the SMEs input on progress made by individual awardee, progress made towards the overall goals of the TEN, and any changes in scope or governance that might help the make the output of the TEN more effective and useful to the biomedical community. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this FOA.

Application Types Allowed The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA. Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NICHD intends to commit $2,000,000 in FY 2023 to fund applications that fit its scientific interests. NIDA intends to commit $500,000 to support applications that fit its scientific interests.

Other NIH entities may commit additional funds to support their scientific interests. Application budgets are limited to $750,000 in direct costs (excluding consortium F&A) per year and need to reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum project period is 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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 Asian American Native American Pacific Islander Serving Institutions (AANAPISIs) Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) 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 Recognized) Eligible Agencies of the Federal Government 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) 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 and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

System for Award Management (SAM)– Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 .

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide. This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2. 3.

7. 4 Submission of Resubmission Application . This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application. An application that has substantial overlap with another application pending appeal of initial peer review (see 2. 3.

9. 4 Similar, Essentially Identical, or Identical Applications ). Section IV.

Application and Submission Information 1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution.

Links to apply using ASSIST or Grants. gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (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 review. 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 plan the review. By the date listed in Part 1.

Overview Information , prospective applicants are asked to submit a letter of intent that includes the following information: Descriptive title of proposed activity Name(s), address(es), and telephone number(s) of the PD(s)/PI(s) Names of other key personnel Participating institution(s) Number and title of this funding opportunity The letter of intent should be sent to: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: A significant time commitment (3.

0 person months) should be made between the Principal Investigator(s), and for MPI applications each PI having no fewer than 1. 2 person months. Applicants should describe the budget associated with meeting the needs of their Resource Sharing Plan.

Budgeting should include travel and lodging for representatives of the Center to attend: Annual meetings of the Transporter Elucidation Network PDs/PIs; Ad hoc meetings called by the TEN SC or the NICHD to discuss research findings and plan cooperative projects, to promulgate data sharing, and to discuss standardization of procedures across the Transporter Elucidation Network.

All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: TEC applicants must propose either (A) functional transport studies in at least two of the following tissues - the human placenta, lactating mammary gland, developing gut, or blood brain barrier or (B) include an informatics/screening component for SLC and/or ABC transporters and functional transport studies in at least one of the following tissues - the human placenta, lactating mammary gland, developing gut, or blood brain barrier.

Specific Aims : The Specific Aims should describe the overall vision for the proposed Transporter Elucidation Center (TEC) and how it will meet the Research Objectives as stated above in this FOA. Explain the critical barriers to progress in elucidating transporter characterization and function and how the proposed Specific Aims will contribute to a solution.

Explain how the proposed project will improve scientific knowledge and research infrastructure by generating and using new data, tools, and/or experimental approaches. Research Strategy: Organize the Research Strategy into sections on: Significance, Innovation, and Approach.

Significance: For the proposed Transporter Elucidation Center, describe: The importance of the problems and critical barriers to advancing the functional understanding of transporters that the proposed TEC will focus on; How the resources of the proposed TEC will improve scientific knowledge and research infrastructure, and how it will ultimately enable future projects on transporters; How the concepts, methods, technologies, and/or approaches used to understand drug and nutrient transporter will be changed if the proposed aims are achieved; How the TEC will foster the training and career development of a diverse set of students, post-doctoral fellows, and junior faculty.

Innovation: For the Transporter Elucidation Center, address: How the proposed research seeks to shift current understanding of transporter proteins and/or drug and nutrient transport through the generation of novel data, tools, and/or technologies; Describe how the project will leverage and capitalize, but not duplicate, previous efforts and approaches such as those undertaken by KOMP, RESOLUTE, etc. Approach: Applicants should address, at a minimum, the following elements: Provide preliminary data indicating the applicants’ ability to conduct the research proposed for the TEC; Clearly define barriers to understanding transporter function that are preventing the advancement of the understanding of drug and nutrient transport; Describe the research that the TEC will undertake and how this research directly relates to barriers in the field; For applications that include an informatics/screening component, explain how that approach will inform research on the placenta, lactating mammary gland, developing gut, and/or blood brain barrier; Explain the importance of the proposed tool/data validation strategy in the context of the development of new information gathered around transporter proteins and their in vivo function; Concisely and adequately describe the capability of the proposed Center to process, analyze, and deposit data into external repositories; Explain how the proposed Center will build upon and not duplicate activities undertaken by other relevant programs, such as, RESOLUTE or KOMP, Provide examples of future research projects relating to transporter characterization and/or drug and nutrient transport not currently possible that will be enabled through enhanced research infrastructure after the completion of the proposed research project; Define the deliverables, timeline, and milestones for the Center and how they align with the goals of this FOA; Articulate how the Center will reprioritize and adjust activities, deliverables, timeline, and milestones on an annual basis (in the RPPR) based on feedback from the Transporter Elucidation Network Steering Committee (TEN SC), external Subject Matter Experts, and NIH staff.

Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. The following modifications also apply: All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Specific Plan for Data Sharing: Consistent with achieving the goals of this program, the NICHD expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publicly available data repositories that are easily accessible, and in machine readable format.

For human data, the NICHD encourages the use of the Data and Specimen Hub (DASH), a centralized resource for researchers to store and access de-identified data from studies funded by NICHD. Where appropriate, applicants should identify such repositories and plans for deposition.

For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://osp. od.

nih. gov/scientific-sharing/genomic-data-sharing/) and should indicate their agreement to it in the data sharing plan. Specific Plan for Protocol, Tool, and Reagent Sharing: In accomplishing the goals of the Transporter Elucidation Centers, it is likely that investigators will develop protocols, tools, and reagents that would be of broad use in the research community.

The NIH intends that protocols, tools, and reagents generated by the Centers be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling downstream investigations in maternal and pediatric therapeutics.

For all applications where applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including models, protocols, biomaterials, and reagents. Specific Plan for Sharing Software: A software dissemination plan is expected in applications that are developing software.

There is no prescribed single license for software produced in this project; however, reviewers will be asked to comment on the software sharing and dissemination plan based on its likely impact. Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others.

This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.

A dissemination plan guided by the following principles is thought to promote the largest impact: The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of training, research institutions, and government laboratories.

The terms should permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages. The software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.

The terms of software availability should include the ability of researchers outside of the Centers and its collaborating projects to modify the source code and to share modifications with other colleagues. An applicant should take responsibility for creating the original and subsequent official versions of a piece of software. Applicants should also be familiar with the NIH statements regarding