Baltimore, MD — Liewei “Leo” Yan, an early-career researcher and member of the Kostova Lab at Carnegie’s Department of Embryology, was awarded a prestigious and highly selective fellowship from the Jane Coffin Childs Memorial Fund for Medical Research. The three-year grant will bolster Yan’s efforts to determine how different types of ribosomes guide complex biological processes, such as embryogenesis and cancer development.
Ribosomes are complex molecular machines that translate messenger RNAs (mRNAs) into proteins, enabling the central dogma of biology. Their function is essential for sustaining life. While ribosomes are found in markedly diverse cellular environments, scientists have traditionally thought that their composition remained static after assembly. Exciting new studies challenge this concept and provide evidence that organisms create different types of ribosomes during development, stress response, or disease.
However, precisely how ribosome diversity impacts translation remains unknown.
Leo Yan examining zebrafish embryos expressing tagged ribosomes under a microscope.
“The field has been held back by a lack of systems that allow the manipulation and purification of ribosome subpopulations, but the zebrafish embryo provides a unique model system to address these limitations,” Yan explained. “Recent studies revealed that zebrafish assemble two ribosome types during embryogenesis: maternal and somatic. These actually have distinct ribosomal DNA sequences, which we predict will lead to structural and functional differences. Our preliminary data show that these ribosomes are very different at every level of their structures, and our ongoing project will determine whether they regulate translation differentially.”
To test this hypothesis, Yan is using tools developed by the Kostova Lab at Carnegie to tag and purify maternal and somatic ribosomes separately in zebrafish. His work will reveal how they differ in their ability to synthesize proteins and identify the mRNAs preferentially translated by each type of ribosome.
“We hope to discover that different ribosomes do indeed function differently and translate different messages.” Yan continued. “It will be the first concrete evidence showing how ribosome heterogeneity regulates translation. It is really exciting!”
Visit kostovalab.org to learn more about Carnegie's ribosome research.