Molecular Mechanisms Linking Nucleolar Function to Hypoxia, Inflammation and Aging

• lesley.stark@ed.ac.uk

As global life expectancy increases, more people face chronic, age-related diseases such as cardiovascular disease, neurodegeneration, and cancer. To develop targeted interventions and preventative strategies, we need to understand what drives biological aging at the cellular level, and how those same processes link to inflammation, stress, and tissue health.

This PhD project will explore the nucleolus, a fascinating and dynamic structure within the nucleus that plays a key role in ribosome biogenesis and cellular stress response. One of the most striking features of aging cells is a change in nucleolar size: enlarged nucleoli are seen in senescent (aging) cells, while smaller nucleoli are linked to longevity. Yet, how and why these changes occur, and what affects they have on tissue function and disease risk, remains unclear.

Our lab has identified the nucleolar protein, TIF-IA, as a potential regulator of this process. We’ve shown that TIF-IA influences nucleolar size and connects to inflammatory pathways, hypoxic responses, and oxidative stress. TIF-IA also correlates with cancer prognosis and even responds to lifestyle interventions such as exercise. These exciting findings suggest that TIF-IA could be a crucial molecular switch linking the nucleolus to aging and disease.

In this project, you’ll explore in depth the role of TIF-IA in nucleolar function, hypoxia, inflammatory response and cellular aging. You’ll use a combination of molecular and cell biology techniques, omics approaches (kinome, interactome, and proteomics), phenotypic screening, and multiplex immunohistochemistry to uncover how nucleolar signalling affects tissue homeostasis and disease susceptibility.

This is an excellent opportunity for a motivated student who wants to:

• Investigate cutting-edge questions in cellular aging and stress biology
• Gain hands-on experience with advanced molecular and imaging techniques
• Work in a collaborative, multidisciplinary environment at the interface of cell biology, aging research, and translational medicine