All cells are surrounded by a membrane that separates their fragile internal machinery from the external environment, however, they also rely on external molecules and nutrients, known as substrates, for their survival. Cells have developed a tightly controlled process of moving these substrates across the membrane via specialised transporter proteins. Solute carrier transporters (SLCs) make up the largest family of these transporters in the human body and are responsible for nutrient uptake, waste removal, ion transport, and even transport of synthetic drugs. Given their widespread importance it is no wonder that SLCs are linked to several pathologies, including many metabolic and neurological diseases.
Despite their vital roles in normal and pathogenic human physiology, up to 30% of SLCs have no known function and remain uncharacterised, classified as “orphan” transporters (Goldmann et al., 2025). I aim to discover how we can identify the structure and functions of an orphan SLC, MFSD14A. This involves answering questions such as 1. What substrates can it bind? 2. What is the overall structure of this membrane transport protein? 3. What mechanism is used to transport these substrates?
During my PhD I will use both functional assays and structure determination techniques such as GFP thermal shift assays, Cryo-electron microscopy, X-ray crystallography, and structure prediction software to de-orphanise this transporter. Upon this project’s completion I hope to contribute to the ever-growing field of membrane transport research, and expand our understanding of the human body to aid in disease treatment and drug discovery.