Cytokines are small protein messengers that transmit information from the outside of the cell to the inside of the cell. Signals initiated by cytokines control many processes including blood cell development, immunity and inflammation. When the transmission of these messages is disrupted by genetic mutations, it can result in inflammatory disease, autoimmunity or cancer.
Our research is focused on determining how these pathways function, how the signals they send are regulated, and how mutations can disrupt these normal processes to cause disease.
A key tool in our research is visualization of these molecules using structural biology techniques. This project will involve the expression and purification of proteins involved in cytokine signaling and determining the structure of these proteins using cryo-electron microscopy and X-ray crystallography. It will also involve detailed biochemical analyses of the proteins and their interaction partners.
The Kershaw lab combines structural biology (X-ray crystallography and cryo-EM) with detailed mechanistic biochemistry and protein chemistry, with the view that a detailed mechanistic understanding of protein function will reveal new opportunities for drug design.
We have a strong focus on understanding signalling via the JAK/STAT pathway. We work on many aspects of the pathway, including how receptors engage with cytokines on the outside of the cell, how JAK kinases become activated to transmit signals on the inside of the cell, and how additional proteins interact with these components to tightly regulate precise signalling.