PhD Studentship opportunity: Germplasm transport in zebrafish embryo

The cells that go on to become the eggs and the sperm in animals, called the germ cells, carry a characteristic material called germ granules (see Figure 1). In some organisms like the zebrafish, these germ granules are present in the embryo and no new germ granules are produced over the lifetime of the organism. As the organism develops into an adult, the granules present in the single-cell embryo make their way into the germ cells. This project is about tracing the first few steps of this incredible journey of the germ granules.

The germ granules [1] are globules of RNA and RNA-binding proteins phase-separated from the cyto- plasm (i.e., the watery fluid occupying most of the embryo). Initially, when the embryo is a single cell, all activity within it is caused by the action of cytoskeletal motor proteins, such as acto-myosin and microtubules. This activity is naturally organized such that the germ granules systematically move and accumulate towards the embryo where cell division occurs (see Figure 1b). This process repeats itself during the next few cell- division cycles. This project is about how the activity within the cell causes this systematic accumulation of germ granules at these specific sites.

The main hypothesis behind the proposal is that, in these early phases of development, a systematic flow is established in the cytoplasm, which transports the germ granules to their destination. Determining the bio-physico-chemical agencies that cause this flow and the factors that control the pattern and strength of the flow are the aims of the project.

During this project, you will use mathematical models of biophysics, i.e. of active matter developed to describe non-equilibrium statistical systems, and apply them to cell mechanics. The equations governing the cell motion are solved computationally, but the focus is on the physical intuition and mechanistic understanding that arises from these solutions. The project is in collaboration with Prof. Karuna Sampath and her group in the Warwick Medical School, which is capable of observing the activity within the embryo and the motion of the germ granules [2]. Her lab can also systematically modify the cellular activity to alter the flow and germ granule motion.

Write to shreyas.mandre@warwick.ac.uk for more information.

Figure 1: Confocal images of zebrafish embryo with molecular fluorescent tags on filamentous actin (red) and germ granules (green). (a) 1-cell stage. (b) 4-cell stage. The germ granules are distributed throughout the single-cell embryo (see panel a), but accumulate at the furrows between the cell at every cell division event (e.g. as shown by the grey arrow at the 4-cell stage). Courtesy: Sampath lab, Warwick Medical School.

References:

[1] T. Treck and R. Lehmann. Germ granules: All about the RNA after all. eLife 6, e24106, 2017. doi: 10.7554/eLife.24106

[2] A. Zaucker, C. A. Mitchell, H. L. E. Coker, and K. Sampath. Tools to image germplasm dynam- ics during early zebrafish development. Frontiers in Cell and Developmental Biology, 2231, 2021. doi:10.3389/fcell.2021.712503