Project Title:

Elucidating the role of macromolecular complexes in vivo

Project Summary:

Cells must effectively regulate protein expression in space and time, the control of which can be achieved through cellular compartmentalisation. Such compartmentalisation was previously thought to be achieved by containing reactions within membrane-bound organelles. However, membrane-less organelles are now understood to provide an additional level of spatial control within cells where reactions can be concentrated without the need for an encapsulating membrane. 
Membrane-less organelles can form through the biophysical phenomenon ‘liquid-liquid phase separation’, whereby two or more liquids can de-mix and separate. This is important in the control of biochemical reactions, for example, phase separation could keep reactants separate, preventing an inadvertent reaction from taking place. Aberrant phase separation can lead to untimely reactions, and this is thought to play a role in causing cancer and Alzheimer’s disease. 
My work investigates the conserved membrane-less organelle ‘processing bodies’ using the fruit fly (Drosophila melanogaster) egg as model systems to understand how the reaction of translation can be controlled. In Drosophila eggs RNAs required to pattern the embryo are localised throughout the egg to their final position where they will eventually be translated and go on to pattern the embryo. Despite being localised they will not be translated until several days later when embryogenesis has started, therefore it is important to segregate mRNAs into processing bodies away from the translation machinery to prevent aberrant translation. My work uses genetics, live imaging, and biochemistry to investigate the factors that enable processing bodies to store RNA for long periods allowing normal development to proceed.