I use the zebrafish to study the development and function of the nervous system. Zebrafish offer numerous advantages as a model organism. First, they develop externally, which means they are readily accessible for studies of embryology and development. Second, they are optically transparent, allowing the dynamics of development to be observed in a living organism. Third, they exhibit robust and reproducible behaviors, which can provide clues regarding potential genetic or neuronal defects. Finally, they are genetically tractable, meaning that it is straightforward to create fish that either completely lack a gene (mutants), or in which a gene product is expressed in excess. Research in my lab focuses on the following topics:
Genetics of somatosensory development and function.
Somatosensory neurons detect thermal (heat vs. cold), mechanical (touch), and chemical (pH, noxious compounds) stimuli. Defects in the development, maintenance, or function of these neurons results in debilitating and important medical consequences such as chronic pain. Through microarray analyses, I have identified hundreds of genes that are specifically enriched by different types of somatosensory neurons. I have begun testing the functions of these genes via genetic gain- and loss-of-function studies. I use two approaches to identify defects in somatosensory development and function: (1) live imaging of transgenic embryos that express GFP in sensory neurons, and (2) high throughput behavioral studies of larval responses to somatosensory stimuli.
Neuropeptide modulation of arousal.
Setting proper arousal state is crucial for appropriate motor behaviors and cognitive function, and is essential for survival. Though the neuroanatomical basis of arousal is well-described, relatively little is known about the molecules that act upon this system to set and modulate arousal levels. Neuropeptides - secreted molecules that mediate communication among neurons - are poised to regulate arousal. I use transgenic fish that inducibly overexpress various neuropeptides to dissect their effects on different components of arousal, from sleep/wake behaviors to responsitivity to stimuli. Future work will explore the role of neuropeptides in anxiety-related behaviors.
Dissection of complex and diverse neuropeptide function.
Neuropeptides have a very wide array of functions, including control of appetite, regulation of pain, stimulation of cell division, control of blood flow, and many others. A single neuropeptide can play many different roles throughout an animal. This breadth of neuropeptide function makes it difficult to pinpoint their precise activities in a single biological process. Compared to mammals, zebrafish often have duplicate copies of genes. In the case of neuropeptides, these duplicates can be advantageous because each duplicate may fulfill just one or a few of the many functions regulated by the analogous mammalian gene. I have identified a mammalian neuropeptide that is represented by five duplicates in zebrafish. By studying these genes individually, I will be able to dissect the various functions performed each of these genes one-by-one. For example, overexpression of one of these duplicates results in increased responses to somatosensory stimuli, while a knockout of this gene results in the opposite phenotype. Currently I am working to develop knockouts and overexpression lines for the remaining four duplicates.
