Targeting cytokine signaling in blood cancer and inflammation: a structural biology approach

• Honours
• Masters by Coursework
• Graduate Research Masters
• PhD

Cytokine signalling controls 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 we can use the information to design new treatments for disease.

This project will use structural biology, protein biochemistry and cell biology to understand the molecular details of cytokine signalling and how they impact diseases such as blood cancer and inflammation. We study many different aspects of this process, and therefore this flexible project offers scope for the candidate to explore to following techniques:

• X-ray crystallography
• Cryo-Electron Microscopy
• AI-guided generation of designer proteins
• Protein Production and Purification
• Fluorescence Microscopy

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.

The Kershaw lab works in close collaboration with the Babon lab.

References:
Sarson-Lawrence KTG, Hardy JM, et al. Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin. Nat Commun. 2024 Feb 7;15(1):1135
Liau NPD, et al. The molecular basis of JAK/STAT inhibition by SOCS1. Nat Commun. 2018. 19;9(1):1558
Morris, R, Kershaw NJ, Babon JJ, The molecular details of cytokine signaling via the JAK/STAT pathway, Protein Sci, 2018 27(12):1984 (REVIEW)