Cell polarity and RNA localisation
oskar mRNA on the move. Time projection of a squash of ooplasm from a stage 9 oocyte imaged with TIRF microscopy. oskar mRNA (labelled with MS2-MCPGFP, shown in rainbow colours) utilises microtubules (labelled with mCherrya1- tubulin and EB1-Cherry, shown in gray with cyan tips, indicating plus ends) to take fast, long linear runs.
A Drosophila egg-chamber, showing colocalisation of oskar mRNA, Staufen protein and a microtubule polarity marker at the posterior of the oocyte.
The Ephrussi group seeks to understand the mechanisms regulating basic cellular processes in a developmental context, in the fruit fly.
Previous and current research
Polarity is a main feature of eukaryotic cells, underlying cell fate decisions, as well as many basic cellular functions and developmental processes. Cell polarisation involves the specific organisation of cytoskeletal structures and regulated targeting of organelles and molecules, including RNAs, to specific subcellular locations. Intracellular RNA transport coupled with localised translational control is a highly prevalent, conserved and powerful mechanism contributing to the functional polarisation of cells.
In Drosophila, asymmetrically localised cell fate determinants localised in the egg specify the body axes and patterning of the future embryo. During oogenesis, the key determinants – bicoid, gurken and oskar – are transported as mRNAs to specific sites within the oocyte, where they are anchored and locally translated, ensuring spatial restriction of their activities. The cytoskeleton and specific motor proteins mediate mRNA transport and anchoring within the cell. We use these RNAs as models to understand how RNA localisation and translational control are regulated in space and time.
Drosophila is ideally suited for genetic, biochemical, and cell biological investigation of the processes of cell polarisation, mRNA localisation and translational control. We make use of this model system to study:
- cytoskeletal polarisation
- the assembly of the RNA transport complexes, and their association with motors and the cytoskeleton mediating their movement
- spatial control of translation within cells.
Future projects and goals
Combining genetics, biochemistry and a broad spectrum of cell biological and imaging approaches, we are investigating:
- the mechanisms underlying cell polarisation
- the role of the cytoskeleton and motors in mRNA transport
- the architecture of transport RNPs: the cis-acting RNA elements and interacting proteins, and how they assemble and associate with their motor proteins to form functional RNA transport complexes
- the mechanisms coupling mRNA transport and translational control.
Our goal is to understand the basic mechanisms underlying RNA transport and spatial control of translation, and how they cooperate in patterning the embryo.