4 YEAR PhD IN NEUROSCIENCE
Department of Cell and Developmental Biology
Circadian clocks in zebrafish
Our group studies the function of the circadian clock and light-dependent resetting using adult zebrafish tissues, embryos and cells. We have previously demonstrated that circadian clocks are widely distributed throughout most tissues in the animal, and perhaps more surprisingly, that these tissues all appear to be light responsive. One of our aims, therefore, is to determine the photopigments and signalling events involved in setting this clock. Furthermore, we have developed transgenic animals and cell lines, containing luminescent reporter genes, which allow us to image circadian changes in gene expression over many days in living animals and cells.
A range of potential projects include:
1) We believe that the clock is present within all neurons in the zebrafish and that all cells contain a novel photopigment. However, at this time, we have no clear evidence of what the clock and light might be regulating within neural tissue. As described above, we have established luminescent approaches to measure clock/clock-regulated gene expression in living cells. One aim is to determine what genes in the nervous system are clock-regulated, to isolate the upstream promoter regions of these genes and then generate “glowing” transgenic animals to study the regulation of these changes in vivo.
2) The pineal gland appears to be one of the earliest structures to develop in the zebrafish embryo, with a functional photopigment expressed as early as Day 2 of development. The role pineal melatonin may play in development or function of the nervous system is not known, nor where within the developing nervous system melatonin may act. We intend to generate a range of “morphant” animals in which melatonin production, and the light response, is disrupted, and then examine the consequences on downstream neural and reproductive function.
Whitmore, D., Foulkes, N. and Sassone-Corsi, P. (2000)
Light directly sets the circadian clocks of zebrafish organs and cells.
Nature (2000) 404:87-91.
Whitmore, D., Cermakian, N., Crosio, C., Foulkes, N., Pando, M., Travnikova, Z., and Sassone-Corsi, P. A (2000)
Biological Chemistry (2000) 381:793-800.
Whitmore, D., Foulkes, N., Strahle, U., and Sassone-Corsi, P. (1998)
Rhythmic expression of the clock gene reveals peripheral circadian pacemakers in Zebrafish.
Nature Neuroscience. (1998) 1:701-707.