Our research addresses two questions:
(i) vertebrate embryogenesis-how do signals, non-coding RNAs, and chromatin influence the fate and movement of cells?
(ii) behavior – how do neuropeptides and neural circuits regulate locomotion, sleep, and learning?
We mainly use zebrafish as a model system, because genetic and imaging approaches can be combined to study complex behaviors and developmental processes in a vertebrate.
1. Vertebrate embryogenesis
The vertebrate body plan is set up during gastrulation, when a ball of undifferentiated, totipotent cells is transformed into an embryo. This process results in the formation of the three germ layers (ectoderm, mesoderm, and endoderm) and the three axes (anterior-posterior, dorsal-ventral and left-right). We wish to understand how signaling pathways, transcription factors, chromatin modifications and non-coding RNAs regulate this process. We are using genetic, biophysical and in vivo imaging approaches to determine how signals move through fields of cells, elicit concentration dependent effects and modulate the fate and migration of cells. In parallel, we use genomic and genetic approaches to determine how chromatin modifications and non-coding RNAs regulate early development.
The genetic and cellular mechanisms that control sleep and wake states remain largely elusive. We have established zebrafish as a model system for sleep research. Zebrafish have the basic hallmarks of sleep-like behaviors. Sleeping fish require stronger stimuli than awake fish to initiate movement and sleep deprivation is followed by increased sleep. In addition, the zebrafish brain expresses peptides that have been implicated in human sleep disorders. We are using genetic and pharmacological screens to isolate sleep regulators and use imaging approaches to dissect sleep circuits. More recently, we have begun to develop assays for learning and memory in zebrafish and have used calcium imaging to identify neurons involved in learning.