Wen Kin Lim

PhD thesis: Investigating the contribution of ribosome dysfunction to decreased proteostatic capacity of aged stem cells

My project will examine a core trait of ageing, the loss of proteostasis (capacity to balance cellular proteins).

With ageing, tissues decline in homeostatic and regenerative capacity i.e., they lack the ability to maintain balance. Ribosomes, molecular machines in all cells, and mRNA translation start to become more error prone with age. Ribosome ‘stalling’ occurs, like a traffic jam in the protein-making process where the machine pauses unexpectedly, causing issues in cell renewal.

What we don’t know is what causes ribosome stalling and exactly how it contributes to proteostatic decline. During my PhD, I will examine protein degradation and stem cell behaviour of Drosophila fruit flies. These are excellent models because of their short lifespans and similarities to mammalian stem cells.

I will determine how ribosome dysfunction contributes to proteostatic decline, which can reveal potential therapeutic interventions to preserve stem cell function and help us understand the mechanisms of ageing.

Who or what inspired you to pursue your research interests?

I am deeply curious about the fundamental question of why and how we age. The spark of my interest was in my second undergraduate year where I studied lifespan extension in C. elegans and learned about Cynthia Kenyon’s discovery that a single gene mutation could double the lifespan of C. elegans.

From this initial interest, I read more papers and took courses to further understand the hallmarks of ageing but was surprised that modern science had so few integrated answers to how we age. Answering this “age-old” question and its implications for preventing age-related diseases motivates my research interests.