Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
June 3, 2020
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)
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)
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:
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
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Although NIMH and NINDS is not listed as a Participating Organization in all the FOAs listed above, applications for this initiative will be accepted.
Scientific/Research Contact(s)
Abigail Soyombo, Ph.D., MBA
National Institute of Mental Health (NIMH)
Telephone: 301-827-7329
Email: [email protected]
Manuel Moro, DVM, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-480-1796
Email: [email protected]
Julia Shaw, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3711
Email: [email protected]
Amy C. Lossie, PhD
National Institute on Drug Abuse (NIDA)
Telephone: (301) 827-6092
Email:[email protected]
James Gnadt, PhD
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9964
Email:[email protected]
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: [email protected]