Scholar Profile

Piali Sengupta

Associate Professor
Department of Biology
Brandeis University
415 South Street
Waltham, MA 02454
Voice: 781-736-2686
Fax: 781-736-3107
Email: piali@volen.ccs.brandeis.edu
Personal Homepage
1996 Searle Scholar

Research Interests

Development and function of chemosensory neurons in C. elegans

Sensory neurons receive stimuli from the environment and transmit this information to the neuronal circuitry of an animal. In the olfactory system, the nature of the stimulus is sorted partly by the sensory neurons themselves. Each of the thousands of similar olfactory neurons responds to only a subset of odorant stimuli. Thus, each olfactory neuron is uniquely identified by its sensory properties. This olfactory specificity is partly mediated by the expression of specific olfactory receptors in each neuron. We are interested in understanding how an olfactory neuron acquires and regulates its characteristic properties.

The nematode C. elegans provides an excellent model system in which to study the development and function of chemosensory neurons. Worms respond to a large number of chemicals using a simple nervous system consisting of 302 neurons, of which 32 appear to be chemosensory. The functions of many of these chemosensory neurons have been defined by killing single neurons and observing the effects of this on the behavior of the worms. Mutants with defects in the responses to various subsets of chemicals have been identified, and several genes defined by these mutations have been cloned. Recently, we have also identified multiple families of candidate chemosensory receptors in the worm.

We will explore how the fates and functions of the chemosensory neurons in the worm are specified. Using a behavioral screen, we have identified a gene odr-7, that encodes a member of the nuclear receptor family of transcriptional regulators. odr-7 is expressed only in the AWA olfactory neurons. In odr-7 mutants, the AWA neurons develop normally but lack all sensory function. Thus odr-7 may regulate the expression of signalling molecules that provide AWA with its unique sensory profile. We have recently shown that a target of odr-7 regulation is the gene odr-10. odr-10 encodes a seven transmembrane domain receptor for a volatile odorant sensed by the AWA neurons. We shall examine the regulation of odr-10 by odr-7, and identify other genes that may also regulate odr-10 expression. Additionally, we will examine how odr-7 specifies AWA function, by identifying genes that act upstream and other genes downstream of odr-7. Thus we may define a cascade of regulatory events that ultimately lead to the correct specification and function of a particular olfactory neuron type.

We plan to use the candidate chemosensory receptor genes as markers to determine how the fates and functions of other chemosensory neurons in the worm are determined. Using genetic screens and behavioral assays, we will identify genes that are required for the development and function of these neurons, as defined by the expression of the appropriate receptor genes. We will also define the mechanisms that are required for the spatial and temporal regulation of these receptor genes, and examine their regulation by the animalsD environment and experience. These experiments will allow us to understand the mechanisms that the animal uses to generate neuronal and olfactory diversity.

We are also interested in investigating the roles of nuclear receptors in the development of the worm sensory system. Although nuclear receptors have been implicated in pattern formation and tissue differentiation in many organisms, their roles in the development of the worm are largely unknown. We will explore the possibility that odr-7-like genes function to specify other sensory cell types in the worm. We have identified a gene nhr-22, that is homologous to odr-7 and is expressed in many sensory neuron types. We shall examine the roles of nhr-22 and other nuclear receptors in the development and function of the chemosensory system of the worm. It is hoped that this research will provide new insights into how the functional complexity of the nervous system is achieved.