Molecular Developmental Biology at MIT

Research

The balancing of cell growth with cell division determines the overall rates of cell proliferation and the emergence of form and function during metazoan development. The commitment to growth and, consequently, proliferate or differentiate is underpinned by a cell’s protein synthesis capacity, which in turn is conferred by the availability and regulation of ribosomes—the protein synthesis machinery of the cell. The way in which protein synthesis allows cells to coordinate their growth with their division remains largely unclear. Therefore, our goal is to study this fundamental aspect of biology by elucidating how cells build ribosomes and how customizing ribosome function impacts the output of protein synthesis of specific cell types and tissues.

 

Ribosomes in Development and Disease

Ribosome assembly and function are regulated during development. Defects in ribosome assembly or function result in tissue specific disorders. We use zebrafish as a model system to study the developmental and tissue specific functions of ribosomes.

 

Growth and Protein Synthesis Control in Stem Cells

All the proteins in a cell are synthesized by ribosomes in a highly regulated manner. Protein synthesis rates vary across different tissues and even within closely related cell types in the same tissue. Stem cells exhibit lower rates of protein synthesis compared to their progenitor cells. We aim to better understand how ribosomes ensure adequate protein synthesis rates in stem cells.

 

High-Order Assemblies

Ribosomes are assembled in the nucleolus, a multi-component membraneless organelle in the cell nucleus. The architecture of the nucleolus and its assembly into compartments and sub-compartments rely on the unique physical and chemical properties of nucleolar proteins and nucleic acids. By concentrating molecules into compartments while allowing dynamic interactions, the nucleolus very efficiently facilitates the complex biochemical reactions that lead to the assembly of ribosomes. Our goal is to better understand how the organization of cellular matter in this membraneless organelle contributes to its various functions, particularly those related to health, aging, and disease.