The fellowship will enable Mariana to continue her work on the impact of autophagy on the immune response.
"I was delighted to be awarded this Fellowship which will enable me to explore the role of autophagy in the renewal of T cells. My ultimate goal is to understand how autophagy impacts lymphocyte stemness, which may potentially lead to new regenerative medicine strategies."
Autophagy, the body's process of reusing old and damaged cell parts, is a key mechanism for cellular differentiation, particularly for the establishment of long-term T cell memory which is key for fighting infection. When autophagy is impaired, for example by ageing, this is accompanied by decreased T cell diversity and inefficient memory responses. Similarly, asymmetric cell division (ACD), a mechanism that leads to daughter cells inheriting different fate determinants, is also compromised with ageing. As both autophagy and ACD are required for T cell differentiation, unravelling how they synergistically impact T cell stemness is at the centre of this project. It will investigate (1) how asymmetric autophagy is built, and (2) whether autophagy/ACD loss functionally impacts immune responses by preventing the establishment of asymmetric fates.
Edward hopes that his research might uncover novel ways to control T-cell function for therapeutic benefit.
"I was thrilled to be awarded the fellowship where I will study how T cells integrate information from their environment, using proteomics, cutting-edge live 4D imaging and computer vision approaches to dissect intracellular signaling cascades. My overall goal is to understand the molecular basis for key behaviours of T cells; how they migrate, scan and kill target cells."
To effectively combat infections and malignant cells, T cells must rapidly migrate through tissue, efficiently scan targets for abnormalities, and kill infected or cancerous cells. These functions all depend on the concerted remodelling of their actin cytoskeleton. Actin remodelling is highly complex, influenced by many internal and external signals, and it remains unclear how T cells integrate this information to achieve these key functions and ensure a successful immune response.
Key to controlling the actin cytoskeleton is a family of proteins, which will be the focus of the study. Using the state-of-the-art microscopy and computer vision techniques at the Kennedy Institute, Edward will try to visualise and manipulate the signaling cascades and external signals that control actin dynamics, and how these sources of information might alter the behaviour of T cells.