Notice of Special Interest (NOSI): Chimerism in Marmosets and other New World Primates
Notice Number:
NOT-MH-20-048

Key Dates

Release Date:

June 3, 2020

First Available Due Date:
October 05, 2020
Expiration Date:
January 08, 2022

Related Announcements

PA-20-185 - NIH Research Project Grant (Parent R01, Clinical Trial Not Allowed)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21, Clinical Trial Not Allowed)

Issued by

National Institute of Mental Health (NIMH)

National Institute on Aging (NIA)

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute on Drug Abuse (NIDA)

National Institute of Neurological Disorders and Stroke (NINDS)

Purpose

The purpose of this Notice is to inform potential applicants to the National Institutes of Health (NIH) about a special interest in research project applications focusing on understanding the biological basis and functional implications of chimerism in the common marmoset (Callithrix jacchus) and other callitrichid primates. Of interest are applications that focus on the following areas: 1) stem cell exchange in utero, the extent and molecular mechanisms associated with the induction and maintenance of hematopoietic chimerism, and the possibility of somatic and/or germ line chimerism in the adult animal; 2) development of systems and assays to study cellular heterogeneity resulting from chimerism and potential intragenomic conflict within an individual’s tissues; and, 3) understanding the molecular and cellular impact of chimerism on biological processes, including development, metabolism, cognition, social behavior, aging, immunological suppression and reactivity, and reproduction; as well as effects on and mechanisms associated with transplant tolerance.

Background

Nonhuman primates (NHP) are the closest evolutionary relatives of humans, with whom they share anatomical, physiological, and gene interaction features. The common marmoset (Callithrix jacchus) is of increasing importance for biomedical research worldwide, aided by its small body size, shorter life span compared to macaques, and rapid reproductive maturation, making them ideal for genetic and transgenerational research. This New World primate is also known for cooperative social behavior, cognition, and communication, which potentially makes for a good model organism to contribute to our understanding of a wide range of human biology and diseases, and are currently being extensively used to study family interactions, hormonal development, reproduction, infectious diseases, neurodegenerative disorders and age-related hearing loss.

Marmosets are obligate litter bearers with most pregnancies resulting in dizygotic twins that show chimerism in the blood and other cells from the hematopoietic lineage, as a result of in utero exchange of stem cells through placental anastomoses during early development, a process that leads to lifelong chimerism. Chimerism was previously reported in most marmoset tissues including skin, hair, brain, lung, blood, lymphatic tissues, and muscle. However, recent quantitative studies indicate that chimerism is limited to cells of the hematopoietic lineage, and that previous observation of widespread tissue chimerism was likely due to blood or lymphocyte infiltration of those tissues, as fibroblast cell lines from chimeric individuals were not chimeric.

The evolutionary and functional consequences of hematopoietic chimerism, which is unique to marmosets and other callitrichid primates, are currently unknown. It is also not known if chimerism limits or enhances the use of these animals as models for human physiology, health and disorders. For example, studies focused on immune response in the marmoset should be cognizant of the potential confounding effect of chimeric lymphocytes. Therefore, for this model to reach its full translational utility in furthering our understanding of human health and diseases, it is imperative that we achieve a better understanding of the functional consequences of chimerism and its contributions to health, behavior and diseases in New World primates.

Research Objectives

Applications in response to this NOSI should be aligned with the overall purpose, which is to improve our understanding of the biological and physiological significance of chimerism in this NHP model. Research areas include but are not limited to:

  1. stem cell exchange in utero, the extent and molecular mechanisms/pathways associated with the induction and maintenance of hematopoietic chimerism, mechanisms associated with maintenance or loss of chimerism in the bone marrow, blood, thymus, and lymphoid tissues of juveniles and adults; and the possibility of somatic and germ line chimerism in the adult animal;
  2. development of systems and assays to study cellular heterogeneity resulting from chimerism; comparisons of major histocompatibility complex genes and proteins expressed by dizygotic twin pairs; and potential intragenomic conflict within an individual’s tissues; and
  3. understanding the molecular and cellular impact of chimerism on biological processes, including development, metabolism, cognition, social behavior, aging, immunological suppression and reactivity, and reproduction; and medical interventions including organ or cellular transplantation that focus on evaluation of the immune response elicited by a sibling twin or third party donor organ (e.g., kidney, heart, lung) or cellular (e.g., bone marrow or islet) transplant and mechanisms associated with transplant tolerance or rejection.

Application and Submission Information

This notice applies to due dates on or after October 5, 2020 and subsequent receipt dates through January 8, 2022.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice

  • PA-20-185: NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
  • PA-20-195: NIH Exploratory/Developmental Research Grant Program (Parent R21, Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-MH-20-048” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form.

Although NIMH and NINDS is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Abigail Soyombo, Ph.D., MBA
National Institute of Mental Health (NIMH)
Telephone: 301-827-7329
Email: abigail.soyombo@nih.gov

Manuel Moro, DVM, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-480-1796
Email: manuel.moro@nih.gov

Julia Shaw, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3711
Email: julia.shaw@nih.gov

Amy C. Lossie, PhD
National Institute on Drug Abuse (NIDA)
Telephone: (301) 827-6092
Email:amy.lossie@nih.gov

James Gnadt, PhD

National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email:gnadtjw@ninds.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Theresa Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: tjarosik@mail.nih.gov


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