Dr. Kartik Venkatachalam
The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Integrative Biology and Pharmacology
Every organism needs to adapt to changes in its environment to ensure optimal growth and survival. In eukaryotes, the nervous system is responsible for gathering and processing information concerning changes in both the internal and external environments. To achieve this vital task, all organisms employ a variety of sensory modalities. The gathered information is deciphered and processed via complex circuits; ultimately allowing the organism to respond in a manner which is best suited for its survival and growth under the changing conditions. Elucidation of the molecular pathways, signaling networks and neuronal circuits involved in this pas de deux between an organism's environment and its survival is the long-term interest of our laboratory.
TRP channels constitute a super-family of cation channels conserved from yeast to humans. A unifying theme in the physiology of this remarkable family of proteins is that they play fundamental roles in sensory transduction. Not only do they allow organisms to detect changes in the external environment by mediating the classical Aristotelian senses of taste, touch, smell, sight and hearing, but they also allow individual cells and even intracellular organelles to respond to changes in their local environment! Therefore, it is not surprising that many human diseases arise due to mutations affecting TRP channel function.
In our laboratory, we study the physiological functions of TRP channels using Drosophila melanogaster as a model organism. Using a plethora of genetic and cell biological tools available for studying the neurobiology of Drosophila, we are engaged in understanding how these channels sense and transmit information to the nervous system. In addition to identifying the mechanisms involved in channel activation and regulation, we hope to map the neuronal circuits that utilize these channels.
The specifics of the major projects in the lab are detailed below:
Investigation of the mechanisms underlying early neuronal defects in a Drosophila model of a childhood onset lysosomal storage disease called mucolipidosis type IV (MLIV). I generated the Drosophila MLIV model as a post doc. My first study with this model was published in Cell. I am continuing with the characterization of this model in my own lab.
We have recently generated a Drosophila mutant missing the gene encoding a putative endosomal/lysosomal chloride channel (fly homolog of human CLC-7, the gene responsible for juvenile osteopetrosis). We are currently phenotyping these flies and checking for alterations in neuronal function and viability. A recently emerging field involves investigation of the roles played by proteins in the endo-lysosomal cascade in phagocytosis of pathogens and innate immunity. Interestingly, our preliminary results indicate that the clc-knockout flies have a tremendous defect in the clearance of bacterial load. We are currently investigating the mechanisms of this very interesting phenotype-first of its kind linking an endo-lysosomal chloride channel with innate immunity and phagocytosis.
Roles of TRP channels in the development and function of the larval neuromuscular junction (NMJ) in Drosophila. TRP channels have been shown to have many fundamental functions in the nervous system. Our exciting preliminary data indicate that two members of this superfamily of cation channels are involved in synaptic development of the larval NMJ. We are currently following up on our observations.
Regulation of development and feeding by serotonin in flies. This project involves the dissection of the molecular mechanisms underlying the regulation of food-seeking behaviors and developmental paradigms in Drosophila. Using a combination of genetics, cell biology and behavioral analysis, we are identifying the mechanisms involved in serotonin release and the receptors involved in transducing the downstream signals.
Techniques used: Drosophila genetics, cell biology, biochemistry, analysis of Drosophila behavior, study of channel function and physiology in vivo. Since we conduct the majority of our research in Drosophila, students in my lab will be exposed to the plethora of powerful tools available in Drosophila.