
NSF Org: |
IOS Division Of Integrative Organismal Systems |
Recipient: |
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Initial Amendment Date: | July 2, 2021 |
Latest Amendment Date: | July 2, 2021 |
Award Number: | 2103367 |
Award Instrument: | Standard Grant |
Program Manager: |
Joanna Shisler
jshisler@nsf.gov (703)292-5368 IOS Division Of Integrative Organismal Systems BIO Directorate for Biological Sciences |
Start Date: | August 1, 2021 |
End Date: | July 31, 2026 (Estimated) |
Total Intended Award Amount: | $687,031.00 |
Total Awarded Amount to Date: | $687,031.00 |
Funds Obligated to Date: |
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History of Investigator: |
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Recipient Sponsored Research Office: |
1 UNIVERSITY OF NEW MEXICO ALBUQUERQUE NM US 87131-0001 (505)277-4186 |
Sponsor Congressional District: |
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Primary Place of Performance: |
1700 Lomas Blvd. NE, Suite 2200 Albuquerque NM US 87131-0001 |
Primary Place of
Performance Congressional District: |
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Unique Entity Identifier (UEI): |
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Parent UEI: |
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NSF Program(s): | Symbiosis Infection & Immunity |
Primary Program Source: |
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Program Reference Code(s): |
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Program Element Code(s): |
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Award Agency Code: | 4900 |
Fund Agency Code: | 4900 |
Assistance Listing Number(s): | 47.074 |
ABSTRACT
T cells are a critical immune cell type in all vertebrate animals. T cell deficiencies lead to susceptibility to pathogens and increased cancer rates. There are a variety of T cell types and subtypes. Their presence and function can vary considerably across between distantly related species. This project investigates a new T cell, called the ??T cell, that was discovered in a model marsupial, the gray short-tailed opossum. ??T cells are found in marsupials and monotremes like the duckbill platypus. ??T cells, therefore, are ancient and present in the ancestors of all mammals, but for unknown reasons was lost in the placental mammals such as humans. Understanding why they were lost from the placental mammals requires understanding their function in species that still have ??T cells. This project investigates the development, distribution, and patterns of gene expression of ??T cells to gain insights into their function. This project will investigate the function of a novel receptor protein, called TCR?, that defines the ?? T cell. TCR? shares structural similarity to an antibody type called nanobodies. Nanobodies are useful diagnostic and therapeutic tools. If TCR? has the properties of nanobodies it raises the potential for generating these tools in a species easily maintained in standard laboratory animal facilities. This project will provide research experiences for undergraduates transferring from two-year Community College to a four-year, Research-intensive University. Doctoral students on the project will work directly with these undergraduates to gain mentoring experience and enhance their own career skills.
This project investigates the development, distribution, and phenotype of a novel type of T cells, the ?? T cell. All studies will be performed using a model marsupial, the gray short-tailed opossum. ?? T cell function remains unknown and preliminary results support a limited time during postnatal development when they are generated in the thymus, have a limited tissue distribution, and a limited T cell receptor (TCR) repertoire in the adult animal. Using combinations of reverse-transcriptase PCR and single-cell RNA sequencing this project will investigate: 1) the timing and the progression of the ?? T cell developmental stages, 2) the tissue distribution throughout maturation and in the adults along with tissue specific phenotyping at the single cell level, and 3) lastly, investigate if there is an association between the diversity of ??TCR and tissue localization. In addition, this project will use phage display technology to investigate the nature of antigen binding by the ??TCR. Specifically, mRNA isolated from spleens of immunized opossums will be used to create libraries of the putative antigen binding domain of ??TCR using a phage display vector. Clones capable of binding the immunizing antigens will be selected by rounds of panning and characterized further by sequencing to identify the clones that are antigen specific. Once clones are identified these will be used to identify the single cells to associate phenotype with antigen specificity. It is anticipated that these results will provide the basis for testable hypotheses on the function or functions of ?? T cells.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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