Award Abstract # 1919857
Doctoral Dissertation Research: Investigating Genomic and Expression-level Adaptations for Detoxification in Primates

NSF Org: BCS
Division of Behavioral and Cognitive Sciences
Recipient: KENT STATE UNIVERSITY
Initial Amendment Date: August 23, 2019
Latest Amendment Date: June 9, 2022
Award Number: 1919857
Award Instrument: Standard Grant
Program Manager: Rebecca Ferrell
rferrell@nsf.gov
 (703)292-7850
BCS
 Division of Behavioral and Cognitive Sciences
SBE
 Directorate for Social, Behavioral and Economic Sciences
Start Date: September 1, 2019
End Date: August 31, 2023 (Estimated)
Total Intended Award Amount: $30,000.00
Total Awarded Amount to Date: $30,000.00
Funds Obligated to Date: FY 2019 = $30,000.00
History of Investigator:
  • Anthony Tosi (Principal Investigator)
    atosi@kent.edu
  • Morgan Chaney (Co-Principal Investigator)
Recipient Sponsored Research Office: Kent State University
1500 HORNING RD
KENT
OH  US  44242-0001
(330)672-2070
Sponsor Congressional District: 14
Primary Place of Performance: KENT STATE UNIVERSITY
800 E. Summit St.
Kent
OH  US  44240-0001
Primary Place of Performance
Congressional District:
14
Unique Entity Identifier (UEI): KXNVA7JCC5K6
Parent UEI:
NSF Program(s): Bio Anthro DDRI
Primary Program Source: 01001920DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1392, 9179
Program Element Code(s): 760800
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.075

ABSTRACT

Cyanide is a poison that is common among plants and toxic to most animals. Nonetheless, three species of bamboo lemur focus most of their feeding time on various parts of Malagasy giant bamboo, which exposes the lemurs to 12-50 times their estimated lethal dose of cyanide on a daily basis. This project will examine the underlying physiology and genomics of cyanide detoxification in bamboo lemurs. In addition to addressing the decades-old puzzle of how these lemurs are able to consume high levels of cyanide, this study may inform the development of therapies, antidotes, or prophylactics to cyanide exposure in humans. During the course of this work, the PI and co-PI will invite and recruit undergraduates from Kent State University's McNair Scholars Program, whose mission is to help first-generation, low-income undergraduates matriculate to a doctoral degree program. The co-PI will also utilize close ties with Northeast Ohio's public libraries and schools to present this project to students and the general public.

The central questions of this study focus on known routes of cyanide detoxification among mammals. Low doses of the poison can be metabolized by a variety of conserved mechanisms, foremost among which is a pathway that uses sulfurtransferase enzymes. The limiting factors for this mechanism appear to be relative expression levels for these enzymes and the availability of sulfur-donor molecules (e.g., thiosulfate). Therefore, the first working hypothesis of this study is that H. aureus has adapted to detoxify its highly cyanogenic diet through positive selection on genes involved in the metabolism of sulfur or sulfur-containing amino acids. This hypothesis will be tested by assembling and mining a reference-quality genome for H. aureus and comparing it to data taken from a proposed genome assembly for Lemur catta, the most closely related species of dietary generalist. It is further hypothesized that H. aureus detoxifies its high levels of circulating cyanide through adaptive changes to the composition of the bloodstream. This second hypothesis will be tested by transcriptomic and metabolomic methods in order to compare the expression profiles and thiosulfate levels, respectively, of free-ranging H. aureus and captive L. catta. Together, these methods will examine adaptive changes in the H. aureus genome, as well as the whole-blood transcriptome and metabolome, which are related to the exceptional cyanide tolerance of this species.

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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Itoigawa, Akihiro and Fierro, Fabrizio and Chaney, Morgan E. and Lauterbur, M. Elise and Hayakawa, Takashi and Tosi, Anthony J. and Niv, Masha Y. and Imai, Hiroo "Lowered sensitivity of bitter taste receptors to -glucosides in bamboo lemurs: an instance of parallel and adaptive functional decline in TAS2R16?" Proceedings of the Royal Society B: Biological Sciences , v.288 , 2021 https://doi.org/10.1098/rspb.2021.0346 Citation Details

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.

During the lifetime of this grant, co-PI Morgan Chaney made two trips to Ranomafana National Park in southeastern Madagascar, one trip in January, 2020 and another in November, 2023. Between these two journeys, we collected ultra-rare tissue samples from 14 separate lemurs across three species: the primary subject of the research (the golden bamboo lemur, Hapalemur aureus) and two comparison species (the red-fronted brown lemur, Eulemur rufifrons; and the greater bamboo lemur, Prolemur simus). With the assistance of veterinarian Dr. Tsiky Rajaonarivelo, we collected blood draws from six E. rufifrons individuals and five H. aureus. As we originally intended, these draws will be used for work to analyze and identify genes expressed in the blood of bamboo lemurs, but this phase of the project was severely hampered by the COVID-19 pandemic. As a result, all of these samples are still in storage in Madagascar, frozen in a protective solution that will aid in the preservation of the molecular information therein. Future work will build on this project over the next year under the mentorship of co-PI Chaney’s postdoctoral supervisor, Dr. Christina Bergey, at Rutgers University. Additionally, we dissected three previously deceased bamboo lemurs: two H. aureus that had died from natural causes and one P. simus which died in captivity during a recent translocation attempt. All of these deaths were unrelated to the present project. During these dissections, DNA-rich tissues were collected and high-quality DNA was purified from these to be used for genomic sequencing. Additionally, photos and measurements were taken to complete novel descriptions of the specialized or unique anatomical traits of bamboo lemurs. These descriptions are currently in progress, and we expect them to result in one or two peer-reviewed articles.

While our original plan involved the importation of tissues to the United States, the COVID-19 pandemic made this unfeasible. Therefore, after much forethought, we switched strategies to complete all data generation within the country of Madagascar. To this end, we sequenced many gigabytes of genomic DNA using the Oxford Nanopore MinION sequencer. At the time of writing this report, we can confirm at least 700 GB of usable data, and this number will increase as we continue to work through the raw sequencing files generated during the most recent research trip. In all, we are confident that a very complete genome assembly will result from this trove of data in the coming year, and this genome will be crucial in homing in on these lemurs’ adaptations for coping with prodigious amounts of dietary cyanide.

Also during the lifetime of this grant, we collaborated with colleagues to publish an article in the Proceedings of the Royal Society (https://doi.org/10.1098/rspb.2021.0346), and we have an article under review with a second journal (preprint: https://doi.org/10.1101/2023.12.06.570463). Additionally, this grant supported the successful completion of a doctoral dissertation (http://rave.ohiolink.edu/etdc/view?acc_num=kent1681985358621505) and therefore contributed enormously to co-PI Chaney’s scientific training.


Last Modified: 01/13/2024
Modified by: Morgan E Chaney

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