Early embryonic development requires the coordination of many cellular processes that enable the formation of a multicellular organism from a single cell. Many of these changes occur at the molecular level and involve the production of specific proteins at the right place and time. To make this possible, the machinery responsible for the synthesis of proteins, the ribosome, must be stored in the oocyte for extended periods of time. Most of the time, ribosomes must be inactive in the oocyte because most proteins are not needed until later in embryogenesis. How ribosomes are stored in the oocyte has been a long-standing question in the field.
The study of ribosomes is important not only in the context of early embryonic development. Ribosomes are abundant in the cells of all living organisms, where they are responsible for the energy-intensive task of making proteins. To regulate energy consumption and control protein levels in cells, ribosomes are subject to regulation. For example, during starvation, ribosomes associate with proteins that block their function to conserve energy. In certain diseases, such as cancer, the number of ribosomes increases to sustain cell proliferation. Therefore, understanding the mechanisms that control ribosome function may have important therapeutic applications.
The embryo is an ideal system to study ribosome regulation because early embryogenesis occurs in the absence of ribosome synthesis. Using zebrafish as a model organism, the goals of this project were (1) to understand how oocytes store ribosomes, and (2) to investigate whether ribosomes play an active role in regulating protein synthesis during early embryogenesis. In addition to studying ribosomes, we also focused on the molecules that carry the instructions for making specific proteins, the messenger RNAs (mRNAs). Like ribosomes, mRNAs must also be stored for long periods of time and activated only at the right time during embryogenesis.
My research has led to the discovery of novel protein factors that associate with egg ribosomes and mRNAs to repress their function while extending their lifespan. These factors transiently bind to ribosomes and mRNAs, making them available for protein synthesis later during embryogenesis. By studying embryogenesis, we have gained insights into novel ways to regulate protein synthesis that can be applied to other systems and cells.
