Vanna Tran

During cell division, the cell must accurately segregate its chromosomes to its two daughter cells and errors in this process can lead to birth defects and diseases such as cancer. The kinetochore is essential to ensuring that force is transmitted from spindle microtubules to move chromosomes, and here we ask how the kinetochore can do so under high forces without structural failure. This work will provide insight into the structural engineering principles underlying the kinetochore’s robust structure and function, and in the long run inform on possible failures linked to disease.

Healthy cell function relies on properly turning DNA to mRNA to proteins, the necessary building blocks of life. One way the cell regulates protein production is via mRNA quality control — pathways dedicated to degrading problematic mRNAs. My thesis started with the identification of a novel link between a small molecule (polyamine) transporter, and a particular mRNA quality control pathway that responds to stalled protein production. Since then, my research focused on determining the underlying nature of this link. My work revealed that these polyamines are used to modify a critical factor involved in protein production (eIF5A), and that the modification of eIF5A is required for the activation of the mRNA quality control pathway I study. eIF5A is known to decrease in abundancy with age, which in combination with my work, could suggest that disrupted mRNA quality control is an unrecognized consequence of aging. My results expand our understanding of what processes are disrupted by aging, and open the door to identifying potential new therapeutic targets to extend human healthspan.