Notice to Update Research Objectives and Number of Awards for PAS-16-033 "Stimulating Hematology Investigation: New Endeavors (SHINE) (R01)"

Notice Number: NOT-DK-17-016

Key Dates
Release Date:   August 17, 2017

Related Announcements
PAS-16-033
NOT-DK-17-002

Issued by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute on Aging (NIA)

Purpose

The NIDDK, NIA and NHLBI are pleased to announce collaborative support for a newly emerging topic in the field of nonmalignant hematology research through the "Stimulating Hematology Investigation:  New Endeavors (SHINE) (R01)" program (PAS-16-033).  R01 applications proposing to use model organisms and/or human subjects are appropriate.  Incoming applications will be assigned to one of the three participating Institutes according to standard receipt and referral guidelines.

To reflect the inclusion of Remodeling the Hematopoietic Stem Cell Niche topic, Section I. Funding Opportunity Description,has been updated as follows:

Currently:

This Funding Opportunity Announcement (FOA), Stimulating Hematology Investigation:  New Endeavors (SHINE) is intended to promote innovative, high-quality hematology research relevant to the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).  In the SHINE program, NIDDK invites investigator-initiated research project grant applications in specific areas of basic and translational hematology research where needs and opportunities for progress are particularly timely.  Specific research topic areas supported by the SHINE program, as outlined below, will change over time and be updated annually through Notices published in the NIH Guide to Grants and Contracts.

NIDDK has supported basic and translational hematology research since 1950 through a multi-faceted program described on the Institute’s website: http://www2.niddk.nih.gov/Research/ScientificAreas/Hematology .  Over the years, this research has generated important insights and enabling technologies that have not only led to progress in understanding and treating blood disorders but have also contributed to advances in biomedical science generally.  The SHINE program allows NIDDK to maintain a flexible, pro-active role in supporting timely, high impact, leading edge research by the hematology research community.

New scientific knowledge to be achieved through research supported by the SHINE program will vary.
In general, the knowledge gaps and research opportunities addressed by the SHINE program will include those that are defined and highlighted by NIDDK-sponsored workshops and other public meetings.

The overall objectives of the SHINE program are to catalyze discoveries in basic molecular and cellular biology that provide new insights into the pathogenesis, prevention, detection, and potential treatment of disease, to attract new investigators into basic and translational hematology research, to promote productive interdisciplinary research collaborations, and to reinforce interactions and communication between NIDDK and the hematology research community. Because research topics featured in the SHINE program will change over time, the program will be dynamic and reflect evolving frontiers of hematology research needs and opportunities.

(1) As announced in the inauguration of the SHINE program (PAS-10-046, the predecessor of PAS-16-033)), specific topic areas will change to meet timely needs and opportunities for hematology research progress. Applicants are encouraged to contact NIDDK or NHLBI Scientific/Research staff to discuss plans for preparation of an R01 application.

(2) With the publication of this Notice, the following SHINE-eligible topics are encouraged:

• Regulatory Determinants of Hematopoietic Stem Cell Fate.  See:  NOT-DK-12-007.
• Role of Noncoding RNA in Hematopoiesis.  See NOT-DK-14-001.
• Role of Macrophages in Blood Cell Development.  See NOT-DK-15-011.
• Effects of Aging on Hematopoiesis.  See NOT-DK-16-007.
• Metabolic Modulators of Hematopoiesis. See next paragraph.

(3)  The addition of the "Metabolic Modulators of Hematopoiesis" topic was informed by the Mitochondrial Biology Symposium: Novel Roles of Mitochondria in Health and Disease held May 19-20, 2016 by NIDDK in collaboration with NHLBI. Cellular metabolism plays critical roles in energy production, the maintenance of a reservoir of cellular building blocks such as amino and nucleic acids, and coordinating stress and survival responses in most cell types. Hematopoietic cells are likely to require specialized coordination of metabolic processes across their unique stages of development and across their lifespan. Relevant research questions for this new SHINE topic include, but are not limited to:

Do energy requirements of quiescent and differentiating hematopoietic cells differ? What are the specialized regulators that regulate metabolism across their development?
What are the transcriptional regulators facilitating metabolic transitions between quiescent and proliferative hematopoietic cell states in vitro and ex vivo?
What are the metabolic factors that regulate hematopoietic stem cell quiescence, cell cycle, and differentiation in vitro and ex vivo?
How are the structure and function of mitochondrial networks impacted in quiescent, proliferative, and differentiated hematopoietic cell states?
What are the roles of cellular metabolites in epigenetic regulation of non-malignant hematopoiesis?
What are the roles of cellular metabolites in the regulation of hematopoietic differentiation?

Now reads:

This Funding Opportunity Announcement (FOA), Stimulating Hematology Investigation:  New Endeavors (SHINE) ) (see NOT-DK-17-002)  is intended to promote innovative, high-quality hematology research relevant to the missions of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the National Heart, Lung and Blood Institute (NHLBI); and the National Institute on Aging (NIA).  In the SHINE program, NIDDK invites investigator-initiated research project grant applications in specific areas of basic and translational hematology research where needs and opportunities for progress are particularly timely.  Specific research topic areas supported by the SHINE program, as outlined below, will change over time and be updated annually through Notices published in the NIH Guide to Grants and Contracts.

The SHINE program allows ICs to maintain a flexible, pro-active role in supporting timely, high impact, leading edge research by the hematology research community.

New scientific knowledge to be achieved through research supported by the SHINE program will vary. In general, the knowledge gaps and research opportunities addressed by the SHINE program will include those that are defined and highlighted by IC-sponsored workshops and other public meetings.

The overall objectives of the SHINE program are to catalyze discoveries in basic molecular and cellular biology that provide new insights into the pathogenesis, prevention, detection, and potential treatment of disease, to attract new investigators into basic and translational hematology research, to promote productive interdisciplinary research collaborations, and to reinforce interactions and communication between ICs and the hematology research community. Because research topics featured in the SHINE program will change over time, the program will be dynamic and reflect evolving frontiers of hematology research needs and opportunities.

The topic of "Remodeling the Hematopoietic Stem Cell Niche" was informed by a workshop held on April 3, 2017.  For an agenda and a listing of topics discussed, please click here.  Relevant research questions for this new SHINE topic include, but are not limited to:

  • How does the architecture/physical structure of a niche inform stemness and/or differentiation?  What are the key cellular and extracellular components of a niche during development, including adults?
  • What are the key molecules, proteins and non-proteins, in a niche that serve as bioactive peptides, chemo-attractants, cytokines or metabolites?  Use of 2D or 3D culture systems may be appropriate.
  • What are the dynamics/interactions between niche components, Hematopoietic Stem Cells (HSCs) and Hematopoietic Stem and Progenitor Cells (HSPCs)?
  • What is the natural history of a niche through extremes of life, during development and aging?  What changes occur in the niche with age?  What are the mechanisms of niche development?  What is the significance of changing ratios of yellow/fatty to red marrow during aging?
  • What is the capacity of the niche to respond to toxins?  What are the mechanisms of niche regeneration and repair after insults?  How does the niche self-renew?
  • What are the roles of biophysical properties of a niche (such as 3D interactions, shear stress and cell and matrix stiffness) in HSC maintenance, expansion, and fate specification?  Use of 2D or 3D culture systems may be appropriate?

As announced in the previous SHINE FOAs, PAS-10-046 and PAS-13-031, PAS-16-033 continues to meet timely needs and opportunities for hematology research progress.  Applicants are strongly encouraged to contact NIDDK, NIA or NHLBI Scientific/Research staff to discuss plans for preparation of an R01 application.

With the publication of this Notice, the following SHINE-eligible topics are encouraged:

  • Regulatory Determinants of Hematopoietic Stem Cell Fate:  See:  NOT-DK-12-007
  • Role of Noncoding RNA in Hematopoiesis.  See NOT-DK-14-001
  • Role of Macrophages in Blood Cell Development.  See NOT-DK-15-011
  • Effects of Aging on Hematopoiesis.  See NOT-DK-16-007
  • Metabolic Modulators of Hematopoiesis.  See NOT-DK-17-002
  • Remodeling the Hematopoietic Stem Cell Niche.  This Notice.

In addition, Section II. Award Information, Funds Available and Number of Awards is being amended to reflect the increase of funding available for FY 2018.

Currently:
Funds Available and Anticipated Number of Awards
NIDDK and NHLBI intend to fund 6-8 awards, totaling $1,750,000 in accordance with FY2018 funding policies.

Now reads:
Funds Available and Anticipated Number of Awards
NIDDK, NHBLI and NIA intend to fund 9-12 awards in addition to those funding within IC regular funding policies, totaling $3,152,396 for Fiscal Year 2018.

All other aspects of this FOA remain unchanged.

Inquiries

Please direct all inquiries to:

Terry Rogers Bishop, Ph.D.
Hematopoietic Stem Cells, Hematopoiesis, Globin Gene expression
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-7726
Email:  terry.bishop@nih.gov

Cindy N. Roy, Ph.D.
Iron in Hematology, Heme Biosynthesis, Bone Marrow Failure/Myelodysplastic Syndrome, Terminal Erythropoiesis
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-594-8805
Email: cindy.roy@nih.gov

John W. Thomas, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email:  thomasj@nhlbi.nih.gov

Malgorzata Klauzinska, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8276
Email:  klauzing@nih.gov

Rebecca Fuldner, Ph.D.
National Institute on Aging (NIA)
Telephone:  301-402-7748
Email:  fuldnerr@nia.nih.gov

John P. Williams, Ph.D.
National Institute on Aging (NIA)
Telephone:  301-827-6373
Email: williamsj6@mail.nih.gov