Establishing the mechanism of the calcium wave at egg activation
Supervisor: Dr Timothy Weil
Egg activation is a conserved process required to prepare an egg for fertilisation and embryogenesis. In all animals, egg activation is associated with at least one transient increase in cytosolic calcium concentration, a “calcium wave”. The calcium wave is required for resumption of the cell cycle, reconfiguring of the cytoskeleton, cortical granule exocytosis and translation of maternal transcripts.
This project aims to characterise in detail the mechanisms that drive initiation and propagation of calcium waves in eggs at activation. Drosophila is an attractive model of choice for this due to its genetic tractability, imaging options and ease of manipulation. To achieve our goals, we use methods already successfully applied in our laboratory, including in vivo advanced imaging of genetically encoded calcium indicators, genetic analysis of key factors, pharmacological disruption and physical micro-manipulation.
The results from this project are important in understanding the general phenomenon of egg activation providing a platform for testing conserved mechanisms of egg activation in other animals. Moreover, this work will have key implications to the fields of cell biology and more broadly with respect to in vitro fertilisation (IVF) since the cytoplasmic environment of the egg has been shown to be important for increasing the rate of IVF success.
Long-term project outlook (PhD):
A PhD project would build on past work and exciting new data in the lab showing that osmotic pressure and reorganisation of the cytoskeleton are the key factors in initiating the Drosophila calcium wave. Using single and multicolour live cell imaging, this project would aim to test the role of key candidate genes that have been identified as part of this pathway. Biochemistry and forward genetics are further alternative approaches if the candidate factors are shown not to be directly involved. All of these methods are actively being undertaken in other projects within the Weil Lab. Moreover, this project will likely shed light on how calcium functions as a second messenger. This integrates the project with other research fields which aim to understand essential cellular processes including synaptic transmission, skeletal muscle function and the regulation of metabolic pathways.
Sartain CV, Wolfner MF.
Cell Calcium. (2013) Jan;53(1):10-5.
York-Andersen AH, Davis I, Weil TT.
Biol Open. (2015) Mar 6;4(4):553-60.
Imaging Calcium in Drosophila at Egg Activation
Derrick CJ, York-Andersen AH, Weil TT.
J. Vis. Exp. (2016) June 3. e54311.