Semester 1, Week 4: Prof Fabian Spill, University of Birmingham

Academic webpage

Title: The Role of Geometry, Topology and Mechanics in Physiology and Disease

Abstract:

Molecular networks underpin all cellular functions, including metabolism, division, and migration. These networks are frequently altered in disease and are common targets for therapeutic intervention. Many key molecular components are associated with the plasma membrane or are localized within organelles such as mitochondria and the endoplasmic reticulum (ER). Notably, the spatial, geometrical, and topological organization of cells and organelles is highly dynamic and varies with cell type, physiological state, and environmental context. For instance, mitochondria can exist as discrete, spherical structures or as extensive, fused networks, while the ER can adopt sheet-like or tubular morphologies.

A major open question is how the organization of cellular and subcellular structures contributes to physiological regulation and how disruptions in this organization influence disease progression and therapeutic response.

In this talk, I will present recent and ongoing work demonstrating that spatial organization is a key determinant of cellular function. First, I will discuss how mitochondrial architecture influences metabolic pathway activity in the context of diabetes. Next, I will explore how metabolic interactions between cancer cells and stromal cells drive tumour progression. Finally, I will show how the structural organization of the ER into sheets and tubules regulates collective cell migration during wound healing, in a manner that is dependent on cell morphology.