Using Solid-State NMR to Identify Molecular Dynamic Signatures of Extracellular Matrix Dysfunction in Ehlers-Danlos Cells

Using Solid-State NMR to Identify Molecular Dynamic Signatures of Extracellular Matrix Dysfunction in Ehlers-Danlos Cells

Using Solid-State NMR on Biological Samples

Rabiah Ahmed

Dr. Wing Ying Chow, Christopher Dean, Abi Hesson and Dr Adil Safeer

The Ehlers-Danlos syndromes (EDS) are a group of genetic disorders characterised by joint hypermobility, stretchy skin, or fragile skin, which are not well understood and can have a disabling effect on a person’s life. These syndromes are caused by changes in the structure and function of proteins, such as collagen, which comprise the extracellular matrix (ECM). The ECM holds cells together, but not much is known about how changes in its composition and molecular dynamics contribute to the development of EDS. This study will use solid-state nuclear magnetic resonance (NMR) spectroscopy to determine the atomic structure and dynamics of ECM obtained from cell culture of fibroblasts from people with and without EDS. By carrying out quantitative comparison of NMR relaxation spectra of the two types of samples, we aim to find similarities and differences that lead to the identification of molecular signatures of specific subtypes of EDS. We envisage that this research will lead to a deeper understanding of EDS and provide insights into how it develops and operates on a molecular level. In the long term, we anticipate that our work may lead to developing better diagnosis strategies and more targeted treatments.

Ehlers-Danlos Syndrome, Solid-State NMR, Collagen, Extracellular Matrix