Investigating the structure and function of the PIKK family of protein kinase

Many major chronic diseases, including cancer, Type 2 diabetes, and neurodegenerative disorders, are caused by perturbations in the internal communication network of the cells within the body. Signaling molecules, which are an important part of the intracellular communication network, coordinate different processes by relaying signals to switch on or off the proper sets of cellular machineries at the appropriate time. By understanding how these signaling molecules work, scientists hope to understand the molecular basis of different diseases and how to treat and prevent these diseases.

One important group of signaling molecules are the PIKK kinases. PIKK kinases are responsible for regulating cell growth and initiating responses to DNA damage, processes that are often disrupted or exploited in cancer formation and progression. Although recent research has identified the different proteins and protein complexes that PIKK kinases receive signals from or transmit signals to, exactly how these communication events occur at the molecular level remains poorly defined.

Dr. Calvin Yip's research program aims to understand the role of PIKK kinases in cancer progression. He is characterizing the three-dimensional structural and biochemical details of these molecules using an advanced imaging technique known as single-particle electron microscopy. Dr. Yip has obtained the first information on the 3D shape of a signaling complex formed by TOR, a member of the PIKK kinase family. With this foundation, he will use an interdisciplinary approach to combine cutting-edge electron microscopy technology and other biochemical and molecular biology methods to further determine how the TOR signaling complex receives and integrates information and how it sends signals to its targets.

Dr. Yip hopes that by focusing on how TOR and other PIKK signaling molecules carry out their biological activities, he will gain a deeper understanding of the fundamental processes of cell growth regulation. This will help pave the way for the development of new therapeutic approaches against cancer.