| NSF Org: |
IOS Division Of Integrative Organismal Systems |
| Recipient: |
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| Initial Amendment Date: | March 24, 2020 |
| Latest Amendment Date: | March 24, 2020 |
| Award Number: | 1938816 |
| 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: | April 15, 2020 |
| End Date: | November 30, 2024 (Estimated) |
| Total Intended Award Amount: | $591,300.00 |
| Total Awarded Amount to Date: | $591,300.00 |
| 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: |
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
The transition of vertebrates from aquatic to terrestrial environments was one of the most remarkable steps in evolutionary history. The environmental conditions of land ecosystems imposed new physiological challenges to vertebrates including desiccation stress, UV damage and novel pathogens. Lungfish (Dipnoi), the closest ancestors of all tetrapods, aestivate forming a cocoon that covers their entire body and protects them against external aggressions. This cocoon has been viewed thus far as an inert layer made of glycoproteins. The researchers propose that this cocoon is in fact a living tissue that protects the lungfish against pathogen invasion for long periods of time. The goal of this project is to determine the structure and function of lungfish cocoons from both laboratory animals and animals caught from the wild in Tanzania. Another goal is to identify how the cocoon protects the lungfish from pathogens during aestivation and if specific immune mechanisms are involved. The societal outcomes of this proposal are to establish the US as a global leader in STEM research and education and to level the gender gap in STEM both in the US and Tanzania. This will be achieved by cross-training summer programs targeted to increase women and minorities representation in STEM.
This project?s intellectual merit is to investigate novel immunological structures and mechanisms used by vertebrates to adapt to environmental stress. Lungfishes are a good model to answer this question since they can adapt to terrestrial environments under unfavorable conditions. The lungfish cocoon, thought to be an inert mucus layer, has been largely understudied. Preliminary studies indicate that this cocoon may be a living tissue with unique immunological capabilities. Specifically, the researchers hypothesize that the cocoon acts as a living, microbe-trapping structure that utilizes neutrophil extracellular traps (NETs) to halt pathogen invasion during the aestivating months when the lungfish are immobile. A variety of histological, immunological, molecular and sequencing approaches will be used to determine the structure and function of the lungfish cocoon. The immune cells and molecules involved in protection against pathogens in the cocoon will be identified. Laboratory-based experiments will be coupled to field collections. This research has the potential for advances in the fields of evolutionary biology and immunology by characterizing immunological mechanisms that allow lungfish to adapt to dessication stress, a key trait that would allow adaption to terrestrial environments.
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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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
This project aimed to investigate how African lungfish are able to survive in water and land. Previous works reported that African lungfish form a cocoon to survive the dry season in a process known as estivation. Previously thought to be made or hardened mucus, we discovered that the cocoon also contains living cells from the lungfish to form an extracorporeal defense structure. Specifically our work has found that some innate immune cells called granulocytes migrate en masse from several lungfish body sites into the skin to cause drastic inflammation. This inflammation leads to shedding of epidermal layers containing granulocytes that over time become accrued to form the cocoon. Importantly, we uncovered the presence of thick layers of stem cells in the lungfish skin that support this extraordinary remodeling process. Understanding the biology of these stem cells would be critical for human regenerative medicine.
Why is the cocoon critical for successful estivation in African lungfish? We showed the the cocoon contains immune cells and produces molecules with antimicrobial properties called antimicrobial peptides. We found that the cocoon effectively traps bacteria and protects the lungfish skin from bacterial colonization during the vulnerable terrestial phase. We showed that this defense function is accomplished by the presence of granulocyte extracellular traps, that are actively being formed in the cocoon. These traps consist of extracellular DNA and many decorating proteins that can kill microbes.
We have recently been able to confirm our findings in the laboratory in wild African lungfish speciments. We went to Tanzania and partnered with a local team of scientists to sample wild lungfish during the estivation period. Wild cocoon samples also contained epithelial cells and granuloctes. Interestingly, we also found fungi trapped in the cocoons, something we had not observed in the lab because our estivating tanks do not have fungi. We have now characterized several mechanisms of antifungal immunity in the lungfish skin that were previously unknown.
Our project has impacted science and technology in the U.S but also has generated broader impacts. Specifically we have trained many students at the University of New Mexico who have now joing the US biomedical workforce. Furthermore, we cross-trained women scientists in Tanzania via several virtual bioinfomatics workshops.
Last Modified: 02/07/2025
Modified by: Irene Salinas
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