Developing approaches to define the ultrastructure of extracellular matrices rich in hyaluronan – key players in inflammation and reproductive biology

Extracellular matrix (ECM) is found around and between virtually every cell in our bodies and it is this substance that organises cells into organs and provides our tissues with their particular mechanical properties. The polysaccharide hyaluronan (HA) is a ubiquitous matrix component with important roles in many physiological (e.g. in development, reproduction, inflammation and neuronal plasticity) and pathological (e.g. cancer and fibrosis) processes.
Although HA is known to play a wide range of roles in health and disease, how it does this is not well understood. Despite HA being large, it is a very simple molecule, making it intriguing to understand how HA can contribute to such diverse functions. Evidence strongly suggests that the explanation lies in the association of HA with proteins; however, it is not clear exactly how this occurs in molecular terms.
The aim of this project is to develop methods to visualise how proteins are organised within HA-rich matrices. The approach of choice is cryo-electron microscopy (Nobel Prize 2017) correlated with light microscopy. Students are encouraged to contact the supervisors for more information on this project.