Biochemistry

The Effects of Tachykinin Mosquito Odorant Receptors

Peace Iheukwumere
Baylor University 
 

Mosquitoes rely heavily on their olfactory system to detect human-derived odorants that guide host-seeking behavior and facilitate vector-borne disease transmission. Tachykinin signaling, mediated by the tachykinin receptor (tkr), is implicated in modulating neural activity and physiological states, yet its role in regulating mosquito olfactory sensitivity and host-seeking readiness remains poorly understood. This study investigated tkr expression dynamics across tissues and feeding states in Anopheles stephensi, an invasive, urban-adapted malaria mosquito. Transcriptomic profiling of tkr expression revealed elevated expression in the head. starved and sugar-fed mosquitoes but significantly downregulated following a blood meal, suggesting that central tachykinin signaling correlates with host-seeking readiness. Conversely, midgut tkr expression peaked during sugar feeding, highlighting distinct tissue-specificphysiological roles. Systemic injection of dsRNA targeting -tkr achieved robust knockdown of tkr in midgut tissue ({p = 0.0001})., but failed to produce a statistically significant reduction in head expression (p = 0.0516}), indicating potential tissue-specific barriers to systemic RNA interference. While natural post-blood-meal suppression of head tkr supports a regulatory link between tachykinin signaling and host-seeking behavior, functional validation via olfactory and behavioral assays will require targeted head-tissue delivery methods. These findings refine our understanding of tkr regulation in An.stephensi and inform future molecular strategies aimed at disrupting vector-host interactions.
 

Dynamic Interaction of Brevetoxins with Human Thioredoxin Reductase

Oscar Delgado1, 
Florida International University
 

Brevetoxin-2 (PbTx-2) is one of the major algal toxins that exert neurotoxicity in marine mammals and humans during Florida red tide algal blooms. However, a study from our group demonstrates that PbTx-2 can also induce oxidative stress in human cells, indicating that the algal toxin has a broad spectrum of toxic effects associated with human diseases such as cancer, and autoimmune diseases, among others. We have recently discovered that PbTx-2 can inhibit human thioredoxin reductase (TrxR). However, it remains unknown how brevetoxin can modulate thioredoxin reductase activity to cause oxidative stress.  We hypothesize that PbTx-2 interacts with selenocysteine residue in the catalytic site located at the C-terminus of human TrxR (hTrxR), altering the structure of the enzyme and inhibiting hTrxR activity. To test this, we initially used computational modeling and molecular dynamics simulation (MD) to generate the PbTx-2-hTrxR complex with AutoDock and ChimeraX. We then characterized the interactions between PbTx-2 and  hTrx-R. The results showed that PbTx-2 localized primarily at the interface between the two TrxR monomers without directly interacting with the catalytic cysteine/selenocysteine (Cys/Sec) motif, suggesting that PbTx-2 inhibited hTrxR through allosteric interaction with the enzyme. We will determine the dynamic interactions between PbTx-2 with hTrx-R in modulating the enzyme structure and function using the MD analysis. Our studies will provide novel mechanistic insight into PbTx-2-induced oxidative stress and open a new avenue for the development of targets for diagnosis and treatment of algal toxin-related diseases.