Research

Research Area
The molecular basis of olfaction in
insect vectors of disease
The molecular basis of olfaction in
agricultural pests
Computational approaches to
decoding receptor-odor
interactions
Development and patterning of
Odor Receptor Neurons
Analysis of neuronal circuits that
underlie odor guided behaviors

Research Area

The main focus of this laboratory is to understand the molecular, neuronal and physiological basis of insect chemoreception and behavior. At the first level we would like to study odor receptor protein function. At the second level, we would like to analyze neuronal circuits in the brain that are involved in generating odor guided behaviors. Finally we would like to investigate the mechanisms underlying olfactory system development.

Most insects can detect and discriminate between a wide variety of odorants which is critical for a number of behaviors like finding food, mating, and oviposition. Odor molecules are detected by 7-transmembrane Odor Receptor proteins present on the surface of neurons in the olfactory organs. A large family of 60 Odor receptor (Or) genes was first identified in the fruit fly Drosophila melanogaster,which subsequently enabled the identification of similar families from genomes of several other insect species. The odor responses of individual odor receptors can be analyzed in great detail using an array of powerful molecular, genetic, bioinformatic and physiological means. Our lab will employ these approaches to address a number of important problems in entomology and neuroscience.

The molecular basis of olfaction in insect vectors of disease

Insects like mosquitoes, tsetse flies, sand flies, house flies and ticks carry a large number of debilitating diseases like malaria, yellow fever, dengue, lymphatic filariasis, river blindness, african sleeping sickness, chagas disease, plague, west nile virus and typhus. Many insect vectors of disease find their human hosts through the sense of smell. We will study the function of odor receptor genes from these species to better understand the molecular basis of insect-host attraction.

Identification of odor receptors that guide insect - host and insect - insect interactions will provide us with new opportunities in pest control. We will employ high-throughput laboratory based functional assays to identify volatile compounds that can activate, inhibit or block odor receptors very efficiently. These compounds will be tested for behavior modifying effects and for usefulness as trapping agents, repellents, or masking agents.
Measurement of action potentials from single neurons activated by odors in Drosophila sensilla

The molecular basis of olfaction in agricultural pests

A large amount of agricultural crops and stored produce are consumed by insects like flies, moths and beetles. Many of these agricultural pests locate their food using olfactory cues. We will study the function of odor receptor genes from these insects to better understand the molecular basis of host attraction.

Computational approaches to decoding receptor-odor interaction

A fundamental challenge in the field of olfaction is that little is know about how odor receptors can detect a wide variety of volatile chemicals with high degrees of specificity and sensitivity. We are implementing chemical informatic approaches to predict receptor-odor interactions and applying bioinformatics to investigate receptor properties.

Development and patterning of Odor Receptor Neurons

Odor Receptor gene choice

Odor discrimination is based on the differential activities of Odor Receptor Neurons (ORNs), which in turn depend on the odor receptors that the ORNs express. This raises an intriguing problem: how do individual ORNs select, from among a large Or gene family, which receptor to express? An individual ORN class expresses only one or a small number of receptors, an individual receptor is expressed in only one ORN class of the fly, and the system exhibits a highly stereotyped receptor-to-neuron map. In earlier studies we have used computational algorithms and phylogenetic analysis to identify positive and negative regulatory elements. Mutational analysis shows that this formidable problem is solved via three classes of mechanisms: by elements that specify the expression of Or genes in the correct olfactory organ, by positive elements that activate Or genes in a subset of ORN classes within an organ, and by negative elements that restrict expression to only one ORN class. However very little is known about transcription factors that bind to these cis-elements and about the developmental program that determine the appropriate expression pattern of these transcription factors?

Combinatorial code of positive and negative cis-elements pattern one-receptor-per-neuron

We are interested in identifying transcription factors that bind to these cis-regulatory elements. Furthermore we are interested in looking at mechanisms that in turn affect activation of the transcription factor patterns.

Formation of ORN connectivity map

Each of the ~ 40 classes of ORNs also need to send axonal projections to unique stereotypic glomeruli in the antenna lobe. A few axon guidance molecules have been identified that play a role in this process. Identification of axon guidance molecules and mechanisms will be critical for understanding how such a sophisticated olfactory system is set up to during development.
Neurons expressing the same odor receptor send axons to a pair of glomeruli in antenna lobes

Analysis of neuronal circuits that underlie odor guided behaviors

Very little is known about neuronal circuits in the central nervous system that give rise to specific odor guided behaviors. Understanding how the activity of ORNs and neuronal circuits in the central nervous system can give rise to behavior is a challenging task because it is difficult to monitor the activity of the relevant neurons in behaving insects. We would like to utilize the simple and genetically tractable organism D. melanogaster to develop novel imaging methods that may enable tracing of entire circuits of activated neurons. We hope this will provide insight into how chemical cues in the environment are translated into specific behaviors such as attraction, repulsion, discrimination, host-selection, oviposition, alarm behavior, aggression, learning, and mating.

The fruity fly brainNeurons projecting to the antenna lobe

 








          The fruit fly brain                                      Neurons projecting to the antenna lobe

Techniques that are used to address these questions include transgenic approaches, molecular genetic approaches, electrophysiology, behavior assays, expression analysis including microarrays, bioinformatics and imaging techniques.