Pristionchus species are nematodes that associate with specific beetles and represent a poorly understood but highly prevalent type of nematode-insect interaction known as necromeny. The working model for how Pristionchus nematodes maintain specific insect interactions is by intercepting the intra-species communications of their host insects. Given the multitude of nematode associations with insect and mammalian hosts, the beetle-associated Pristionchus pacificus represents a much needed knowledge bridge between the free-living model organism Caenorhabditis elegans and human filarial nematodes such as Brugia malayi and Wucheria bancrofti. This is especially relevant to human health since filarial nematodes also require insect vectors to transmit diseases such as lymphatic filariasis. Knowledge of the molecular physiology of insect pheromone attraction will have a direct impact on our understanding of olfaction in nematodes, which can ultimately translate into improving treatments against parasitic nematodes that afflict an estimated 1.3 billion people worldwide (WHO). Our recent NIH-funded study revealed that a lipid binding protein, OBI-1, mediates host insect pheromone sensing through the cGMP signaling pathway that is found in many sensory cells of animals. OBI-1 belongs to a class of highly conserved but functionally diverse secreted lipid-binding proteins, including lipopolysaccharide-binding proteins (LBPs), bactericidal permeability-increasing proteins (BPIs), and cholesteryl ester transfer proteins in mammals. We hypothesize that the expression of OBI-1 in the glial cells that support chemosensory neurons is required for the nematode's olfactory organ to recognize the beetle pheromone. We speculate that OBI-1 may act as an extracellular receptor chaperone to guide pheromone molecules to membrane-bound receptors, or as a signal terminator to remove the pheromone from membrane bound receptors. Our primary aims are to determine if OBI-1 mediates olfaction through the glial cells and if there is direct interaction between OBI-1 and the pheromone molecule. Our long-term focus is to interrogate how OBI-1 genetically interacts with other factors the cGMP pathway during odor sensing, such as the cGMP-dependent protein kinase (PKG) EGL-4.

Public Health Relevance

Knowledge of the molecular physiology of insect pheromone attraction in nematodes will have a direct impact on our understanding of olfaction in parasitic nematodes that afflict humans and economically important livestocks and crops. Our proposal has the potential to be translated into improving treatments against human filarial nematodes by targeting their means of perceiving their abiotic environment, their insect hosts, and to elucidate the overall diversity of molecular pathways in animal chemosensation.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Continuance Award (SC3)
Project #
Application #
Study Section
Special Emphasis Panel (ZGM1-TWD-9 (SC))
Program Officer
Okita, Richard T
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
California State University Northridge
Schools of Arts and Sciences
United States
Zip Code
Stephens, David E; Nguyen, Vu T; Chhetri, Bhuwan et al. (2016) Organocatalytic Synthesis of Methylene-Bridged N-Heterobiaryls. Org Lett 18:5808-5811
Koneru, Sneha L; Salinas, Heilly; Flores, Gilberto E et al. (2016) The bacterial community of entomophilic nematodes and host beetles. Mol Ecol 25:2312-24
Mfuh, Adelphe M; Nguyen, Vu T; Chhetri, Bhuwan et al. (2016) Additive- and Metal-Free, Predictably 1,2- and 1,3-Regioselective, Photoinduced Dual C-H/C-X Borylation of Haloarenes. J Am Chem Soc 138:8408-11
Herrera, Lizzi; Stephens, David E; D'Avila, Abigail et al. (2016) Insights into the structural patterns of the antileishmanial activity of bi- and tricyclic N-heterocycles. Org Biomol Chem 14:7053-60
Mfuh, Adelphe M; Zhang, Yu; Stephens, David E et al. (2015) Concise Total Synthesis of Trichodermamides A, B, and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core. J Am Chem Soc 137:8050-3
Mfuh, A M; Larionov, O V (2015) Heterocyclic N-Oxides - An Emerging Class of Therapeutic Agents. Curr Med Chem 22:2819-57
Stephens, David E; Lakey-Beitia, Johant; Chavez, Gabriel et al. (2015) Experimental and mechanistic analysis of the palladium-catalyzed oxidative C8-selective C-H homocoupling of quinoline N-oxides. Chem Commun (Camb) 51:9507-10
Cinkornpumin, Jessica K; Wisidagama, Dona R; Rapoport, Veronika et al. (2014) A host beetle pheromone regulates development and behavior in the nematode Pristionchus pacificus. Elife 3:
Stephens, David E; Chavez, Gabriel; Valdes, Martin et al. (2014) Synthetic and mechanistic aspects of the regioselective base-mediated reaction of perfluoroalkyl- and perfluoroarylsilanes with heterocyclic N-oxides. Org Biomol Chem 12:6190-9
Kroetz, Silvina M; Srinivasan, Jagan; Yaghoobian, Jonathan et al. (2012) The cGMP signaling pathway affects feeding behavior in the necromenic nematode Pristionchus pacificus. PLoS One 7:e34464