The long-term goal of this project is to reveal the molecular logic by which bitter tastants are detected and encoded. The experimental plan takes advantage of the fruit fly Drosophila as a model system, which allows incisive molecular genetic analysis of taste genes and physiological analysis of taste function. The project focuses on a large family of Gustatory receptors (Grs), many of which mediate responses to bitter compounds. The project examines the bitter-sensitive neuron that expresses the fewest Grs in the major taste organ of the head.
The first aim will systematically test the functional necessity of each of the Grs expressed in this neuron.
This aim i s designed to test a model in which a network of coexpressed Grs interact with each other both positively and negatively. The analysis will test the hypothesis that some Grs are ?tuning Grs? that bind tastants and that other Grs are coreceptors.
The second aim will systematically test the functional sufficiency of each Gr in the neuron. Using CRISPR technology we will construct an ?empty bitter neuron? that expresses no Grs. We will determine whether individual Grs expressed alone in a bitter neuron are sufficient to confer taste response.
This aim could establish a useful in vivo expression system for taste receptors.
The third aim will systematically examine a receptor in combination with others to identify partners with which it interacts functionally.
The aim will test the hypothesis that there is a combinatorial logic to taste detection, with different combinations of Grs responding to different tastants. This combinatorial logic could enhance the ability of a small number of receptors to detect a large number of tastants. Diseases carried by insects afflict hundreds of millions of people each year. These insects detect their human hosts, their food, or their mates largely through their chemosensory systems. Advances in understanding these chemosensory systems may lead to new means of manipulating them and of thereby controlling insect vectors of human disease.

Public Health Relevance

Insects transmit a wide variety of diseases, including new ones such as Zika, to hundreds of millions of people each year. Many of these insects rely on their chemosensory systems to identify their human hosts, their food, or their mates. This project is designed to elucidate how these systems operate and could lead to new means of manipulating them so as to control these insect vectors of disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC011697-17
Application #
9820242
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Sullivan, Susan L
Project Start
2001-05-01
Project End
2021-11-30
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
17
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Sun, Jennifer S; Larter, Nikki K; Chahda, J Sebastian et al. (2018) Humidity response depends on the small soluble protein Obp59a in Drosophila. Elife 7:
Park, Joori; Carlson, John R (2018) Physiological responses of the Drosophila labellum to amino acids. J Neurogenet 32:27-36
He, Zhe; Carlson, John R (2017) Molecules That Can Rewire the Taste System. Biochemistry 56:6075-6076
Delventhal, R; Menuz, K; Joseph, R et al. (2017) The taste response to ammonia in Drosophila. Sci Rep 7:43754
Joseph, Ryan M; Sun, Jennifer S; Tam, Edric et al. (2017) A receptor and neuron that activate a circuit limiting sucrose consumption. Elife 6:
Delventhal, Rebecca; Carlson, John R (2016) Bitter taste receptors confer diverse functions to neurons. Elife 5:
Stewart, Shannon; Koh, Tong-Wey; Ghosh, Arpan C et al. (2015) Candidate ionotropic taste receptors in the Drosophila larva. Proc Natl Acad Sci U S A 112:4195-201
Joseph, Ryan M; Carlson, John R (2015) Drosophila Chemoreceptors: A Molecular Interface Between the Chemical World and the Brain. Trends Genet 31:683-695
Kwon, Jae Young; Dahanukar, Anupama; Weiss, Linnea A et al. (2014) A map of taste neuron projections in the Drosophila CNS. J Biosci 39:565-74
Koh, Tong-Wey; He, Zhe; Gorur-Shandilya, Srinivas et al. (2014) The Drosophila IR20a clade of ionotropic receptors are candidate taste and pheromone receptors. Neuron 83:850-65

Showing the most recent 10 out of 25 publications