Structural and Transcriptomic-Based Guidance for Identifying Odor-ligand Relationships in Mosquitoes

Authors

Fredis MappinFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Biology

First Advisor's Name

Matthew DeGennaro

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Manuel Barbieri

Second Advisor's Committee Title

committee member

Third Advisor's Name

Timothy Allen

Third Advisor's Committee Title

committee member

Fourth Advisor's Name

Anthony Bellantuano

Fourth Advisor's Committee Title

committee member

Fifth Advisor's Name

Mauricio Rodriguez-Lanetty

Fifth Advisor's Committee Title

committee member

Keywords

olfaction, olfactory receptors, deorphanization, chemosensation, xenobiotic response

Date of Defense

6-27-2023

Abstract

Odor detection is at the center of a mosquito’s ability to detect, discriminate, and navigate to its preferred host. Volatile repellents, however, are an effective form of personal protection against anthropophilic mosquitoes that have the potential to spread diseases. Taken together, this indicates that ORs are both molecular targets underlying attraction and repellent behavior in mosquitoes. An increase in our understanding of these ORs tuning therefore may lead to improvements in vector control strategies. Most ORs in mosquitoes are "orphan", a term indicating a cognate ligand has not yet been identified for the receptor. A major pursuit, therefore, is the development and implementation of novel techniques and strategies for the characterization of olfactory receptors. The modification of odorant receptor mRNA brought on by prolonged odor exposure is strongly correlated with ligand-receptor interactions in Drosophila melanogaster. In this study, we first establish that the mRNA levels of the A. aegypti receptor OR8 respond to exposure to its cognate ligand 1-octen-3-ol in a time and concentration-dependent manner and that the effect is reversible. We then developed an odor-evoked transcriptome (OET) to conduct a genome-wide survey of the transcriptional response to prolonged exposure to 1-octen-3-ol and identified several high-hit OR targets. Most sequence comparisons between olfactory receptors fall into the "twilight zone," where structural identity cannot be determined based solely on sequence similarity alone. Advancement in protein modeling offers novel methods for analyzing sequence/structural relationships and the effect they have on odor response. Here we develop a method of using predictive protein structures to guide the identification of odor-ligand relationships among mosquito ORs. We discover that although most receptors fall into the twilight zone, they are predicted to share remarkable similarities in structure. Furthermore, we determined that protein structures that are predicted to be similar are likely to respond to structurally similar ligands based on a dataset of currently deorphanized receptors. This allows us to build predictive models for response across mosquitoes, furthermore, cluster receptors that are more likely to share similar odor-ligand responses.

Identifier

FIDC011187

Previously Published In

Mappin F, DeGennaro M. CHAPTER 7 - Multimodal mechanisms of repellency in arthropods. In: Corona C, Debboun M, Coats J, eds. Advances in Arthropod Repellents. Academic Press; 2022:113-130. doi:10.1016/B978-0-323-85411-5.00005-4

Mappin F, Bellantuono AJ, Ebrahimi B, DeGennaro M. Odor-evoked transcriptomics of Aedes aegypti mosquitoes. Published online March 19, 2023:2023.03.12.532230. doi:10.1101/2023.03.12.532230

Recommended Citation

Mappin, Fredis, "Structural and Transcriptomic-Based Guidance for Identifying Odor-ligand Relationships in Mosquitoes" (2023). FIU Electronic Theses and Dissertations. 5377.
https://digitalcommons.fiu.edu/etd/5377