Aedes aegypti mosquitoes are the principal vectors for several human diseases including Dengue Fever, which causes ~400 million cases and ~24,000 deaths per year (Bhatt et al., 2013; WHO, 2002). Novel strategies to combat mosquito-borne diseases are needed for A. aegypti and other mosquitoes such as the malaria vector Anopheles gambiae. Our goal was to discover new ways to interfere with the ability of a mosquito to locate a human host for a blood meal. Currently, the mechanistic basis of host-seeking and its regulation remain incompletely understood. Although it is known that mosquitoes require human odor cues to locate a human host, the critical odor components and associated olfactory receptors have not been identified (Klowden, 1995; Takken and Knols, 1999). Previous work showed that mosquito host-seeking behavior is inhibited by a hemolymph-borne humoral factor for three days following a blood meal. Subsequent studies identified Head Peptide-I as a candidate neuropeptide modulating this suppression in host-seeking behavior. This conclusion was strengthened by the observation that Head Peptide-I injection into non-blood-fed females triggered the inhibition of host-seeking. The mechanism by which this important peptide alters mosquito behavior and the receptor through which it signals are unknown (Brown et al., 1994). We used a cell-based calcium-imaging screen to identify the G-protein coupled receptor NPY-Like Receptor-1 (NPYLR1) as a candidate Head Peptide-I receptor. We found that multiple NPYLR1 agonists, including the feeding-related Short-Neuropeptide-3 (sNPF3), are capable of inhibiting host-seeking behavior when injected into non-blood-fed females. To investigate whether NPYLR1 is required for Head Peptide-I inhibition, we pioneered targeted mutagenesis with zinc-finger nucleases to create multiple NPYLR1 null-mutant mosquito lines. We predicted that these mutants would no longer show inhibition of host-seeking behavior after a blood meal. While we can say with certainty that NPYLR1 is a receptor for Head Peptide-I, we found no behavioral effects for NPYLR1 mutants in locomotion, egg-laying, sugar feeding, blood feeding, or host-seeking behavior. Our results suggest that NPYLR1 is not required in vivo for Head Peptide-I action and that a redundant signaling mechanism for behavioral inhibition exists. Future work will determine the necessity of Head Peptide-I during host-seeking inhibition and attempt to identify additional Head Peptide-I and sNPF receptors. This research will clarify the mechanism of Head Peptide-I inhibition and could form the basis for novel strategies to control mosquito host-seeking behavior.
","abstract_html":"<p>Aedes aegypti mosquitoes are the principal vectors for several human diseases including Dengue Fever, which causes ~400 million cases and ~24,000 deaths per year (Bhatt et al., 2013; WHO, 2002). Novel strategies to combat mosquito-borne diseases are needed for A. aegypti and other mosquitoes such as the malaria vector Anopheles gambiae. Our goal was to discover new ways to interfere with the ability of a mosquito to locate a human host for a blood meal. Currently, the mechanistic basis of host-seeking and its regulation remain incompletely understood. Although it is known that mosquitoes require human odor cues to locate a human host, the critical odor components and associated olfactory receptors have not been identified (Klowden, 1995; Takken and Knols, 1999). Previous work showed that mosquito host-seeking behavior is inhibited by a hemolymph-borne humoral factor for three days following a blood meal. Subsequent studies identified Head Peptide-I as a candidate neuropeptide modulating this suppression in host-seeking behavior. This conclusion was strengthened by the observation that Head Peptide-I injection into non-blood-fed females triggered the inhibition of host-seeking. The mechanism by which this important peptide alters mosquito behavior and the receptor through which it signals are unknown (Brown et al., 1994). We used a cell-based calcium-imaging screen to identify the G-protein coupled receptor NPY-Like Receptor-1 (NPYLR1) as a candidate Head Peptide-I receptor. We found that multiple NPYLR1 agonists, including the feeding-related Short-Neuropeptide-3 (sNPF3), are capable of inhibiting host-seeking behavior when injected into non-blood-fed females. To investigate whether NPYLR1 is required for Head Peptide-I inhibition, we pioneered targeted mutagenesis with zinc-finger nucleases to create multiple NPYLR1 null-mutant mosquito lines. We predicted that these mutants would no longer show inhibition of host-seeking behavior after a blood meal. While we can say with certainty that NPYLR1 is a receptor for Head Peptide-I, we found no behavioral effects for NPYLR1 mutants in locomotion, egg-laying, sugar feeding, blood feeding, or host-seeking behavior. Our results suggest that NPYLR1 is not required in vivo for Head Peptide-I action and that a redundant signaling mechanism for behavioral inhibition exists. Future work will determine the necessity of Head Peptide-I during host-seeking inhibition and attempt to identify additional Head Peptide-I and sNPF receptors. This research will clarify the mechanism of Head Peptide-I inhibition and could form the basis for novel strategies to control mosquito host-seeking behavior.</p>","abstract_has_math":false,"creators":["Liesch, Jeff"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Leslie B. Vosshall"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-01-01T08:00:00Z","date_published":"2014-01-01T08:00:00Z","updated_at":"2026-07-24T04:11:21Z","subjects":["mosquito behavior","host-seeking","Aedes aegypti","Head Peptide-I","NPYLR1","neuropeptide signaling","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/221","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Leslie B. Vosshall"]},{"key":"dc:creator","label":"Author","values":["Liesch, Jeff"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["mosquito behavior","host-seeking","Aedes aegypti","Head Peptide-I","NPYLR1","neuropeptide signaling","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/221"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Aedes aegypti mosquitoes are the principal vectors for several human diseases including Dengue Fever, which causes ~400 million cases and ~24,000 deaths per year (Bhatt et al., 2013; WHO, 2002). Novel strategies to combat mosquito-borne diseases are needed for A. aegypti and other mosquitoes such as the malaria vector Anopheles gambiae. Our goal was to discover new ways to interfere with the ability of a mosquito to locate a human host for a blood meal. Currently, the mechanistic basis of host-seeking and its regulation remain incompletely understood. Although it is known that mosquitoes require human odor cues to locate a human host, the critical odor components and associated olfactory receptors have not been identified (Klowden, 1995; Takken and Knols, 1999). Previous work showed that mosquito host-seeking behavior is inhibited by a hemolymph-borne humoral factor for three days following a blood meal. Subsequent studies identified Head Peptide-I as a candidate neuropeptide modulating this suppression in host-seeking behavior. This conclusion was strengthened by the observation that Head Peptide-I injection into non-blood-fed females triggered the inhibition of host-seeking. The mechanism by which this important peptide alters mosquito behavior and the receptor through which it signals are unknown (Brown et al., 1994). We used a cell-based calcium-imaging screen to identify the G-protein coupled receptor NPY-Like Receptor-1 (NPYLR1) as a candidate Head Peptide-I receptor. We found that multiple NPYLR1 agonists, including the feeding-related Short-Neuropeptide-3 (sNPF3), are capable of inhibiting host-seeking behavior when injected into non-blood-fed females. To investigate whether NPYLR1 is required for Head Peptide-I inhibition, we pioneered targeted mutagenesis with zinc-finger nucleases to create multiple NPYLR1 null-mutant mosquito lines. We predicted that these mutants would no longer show inhibition of host-seeking behavior after a blood meal. While we can say with certainty that NPYLR1 is a receptor for Head Peptide-I, we found no behavioral effects for NPYLR1 mutants in locomotion, egg-laying, sugar feeding, blood feeding, or host-seeking behavior. Our results suggest that NPYLR1 is not required in vivo for Head Peptide-I action and that a redundant signaling mechanism for behavioral inhibition exists. Future work will determine the necessity of Head Peptide-I during host-seeking inhibition and attempt to identify additional Head Peptide-I and sNPF receptors. This research will clarify the mechanism of Head Peptide-I inhibition and could form the basis for novel strategies to control mosquito host-seeking behavior.
"]},{"key":"dc:title","label":"Title","values":["The Neuropeptide Regulation of Host-Seeking Behavior in Aedes Aegypti Mosquitoes"]}]}],"canonical_facts":{"dc:contributor":["Leslie B. Vosshall"],"dc:creator":["Liesch, Jeff"],"dc:description.abstract":["Aedes aegypti mosquitoes are the principal vectors for several human diseases including Dengue Fever, which causes ~400 million cases and ~24,000 deaths per year (Bhatt et al., 2013; WHO, 2002). Novel strategies to combat mosquito-borne diseases are needed for A. aegypti and other mosquitoes such as the malaria vector Anopheles gambiae. Our goal was to discover new ways to interfere with the ability of a mosquito to locate a human host for a blood meal. Currently, the mechanistic basis of host-seeking and its regulation remain incompletely understood. Although it is known that mosquitoes require human odor cues to locate a human host, the critical odor components and associated olfactory receptors have not been identified (Klowden, 1995; Takken and Knols, 1999). Previous work showed that mosquito host-seeking behavior is inhibited by a hemolymph-borne humoral factor for three days following a blood meal. Subsequent studies identified Head Peptide-I as a candidate neuropeptide modulating this suppression in host-seeking behavior. This conclusion was strengthened by the observation that Head Peptide-I injection into non-blood-fed females triggered the inhibition of host-seeking. The mechanism by which this important peptide alters mosquito behavior and the receptor through which it signals are unknown (Brown et al., 1994). We used a cell-based calcium-imaging screen to identify the G-protein coupled receptor NPY-Like Receptor-1 (NPYLR1) as a candidate Head Peptide-I receptor. We found that multiple NPYLR1 agonists, including the feeding-related Short-Neuropeptide-3 (sNPF3), are capable of inhibiting host-seeking behavior when injected into non-blood-fed females. To investigate whether NPYLR1 is required for Head Peptide-I inhibition, we pioneered targeted mutagenesis with zinc-finger nucleases to create multiple NPYLR1 null-mutant mosquito lines. We predicted that these mutants would no longer show inhibition of host-seeking behavior after a blood meal. While we can say with certainty that NPYLR1 is a receptor for Head Peptide-I, we found no behavioral effects for NPYLR1 mutants in locomotion, egg-laying, sugar feeding, blood feeding, or host-seeking behavior. Our results suggest that NPYLR1 is not required in vivo for Head Peptide-I action and that a redundant signaling mechanism for behavioral inhibition exists. Future work will determine the necessity of Head Peptide-I during host-seeking inhibition and attempt to identify additional Head Peptide-I and sNPF receptors. This research will clarify the mechanism of Head Peptide-I inhibition and could form the basis for novel strategies to control mosquito host-seeking behavior.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/221"],"dc:subject":["mosquito behavior","host-seeking","Aedes aegypti","Head Peptide-I","NPYLR1","neuropeptide signaling","Life Sciences"],"dc:title":["The Neuropeptide Regulation of Host-Seeking Behavior in Aedes Aegypti Mosquitoes"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:11:21Z"}