Context of the research: How does the brain work? This is one of the most fundamental questions a human being can ask. There are many sides to this question, philosophical as well as biological. My project focuses on particular proteins, the so-called Unc5 receptors, that are located on the surface of cells. Much like a navigation system, these proteins direct brain cells along the right paths and help them connect to each other. This gives rise to the neuronal networks that underlie the functions of our brain. These proteins also direct other cells in our body. For example, Unc5 receptors control the development of blood vessels is. They do this by regulating those cells that are responsible for growing new blood vessels. Some aspects of how Unc5 receptors guide and direct neurons and other cells are understood. Just like a navigator would do, they recognise specific signals (in this case other compatible molecules, referred to as ligands) in their environment. The recognition event involves physical interaction of the Unc5 receptor and ligands. Most ligands of Unc5 receptors also interact with other molecules. The result is a network of interactions, with Unc5 receptors constituting major nodal points. How Unc5 receptors guide cells depends on the surrounding molecules present in its environment. Aims and objectives: How do Unc5 receptors interact with specific ligands, and how do these ligands interact with further molecules? I will study these interactions with high resolution methods to understand the molecular details that define them. Following this, I will use this information to understand the specific biological functions of each of the interactions. For example, I will test what happens when Unc5 no longer recognises one of its ligands. WIll this affect specific cell properties, leaving others unaffected? Will it affect the way that Unc5 moves around on the surface of cells? My experiments will answer these questions by zooming in to the cell surface, using advanced microscopy methods, and by looking at the behaviour of multiple cells, using cell biology assays. Potential applications and benefits: Unc5 receptors are involved in fundamental processes including brain development and blood vessel formation. My results will provide an essential piece to the puzzle of how these processes are regulated. Given this information, could potentially be used to design new drugs related to diseases of the vascular and neuronal systems. Unc5 receptors also play important roles in human cancers. In most cases, cancer cells have a reduced ability to use Unc5 receptors for their guidance. By revealing how Unc5 receptors control cell behaviour, I will also generate knowledge for the specific treatment of cancers with Unc5 receptor-related defects. All information generated by this project will be published and made available for further exploitation. During the course of the project, I will engage in public outreach activities to communicate aspects of my work to a broad community.