We explore how blood cell signalling influences fate decisions during development and immune responses.
This will help to improve immunotherapies for cancer and infectious diseases, and to understand how leukaemia occurs when development goes wrong. Key for our research approach is to develop and apply new imaging and computational approaches; for this reason, the lab is partly located in the Centre for Micro-Photonics, Swinburne University.
Single-cell pedigree analysis to understand the mechanisms of fate determination during T cell development, leukaemia and immune responses
Programming of cell fate determination underpins the appropriate development of all cells, and cancer arises when this programming goes awry. Understanding how cell fate programming works will lead to improved diagnostic and therapeutic opportunities for leukaemia, and to improved immunotherapies for cancer and infectious diseases. We have developed new methods for imaging single cells and their progeny through many generations of T cell development and activation. These methods mean that we can now assemble pedigrees that describe both the relationships between different differentiation stages, and molecular and behavioural attributes of their ancestors and progeny. We are now developing new computational approaches to analyse these pedigrees, and to determine the relative contributions of genetic, epigenetic, extrinsic and stochastic influences on fate determination.
Super-resolution microscopy to study molecular signalling in intact cells
Novel microscopy technologies that were awarded a Nobel Prize in 2014 have created new possibilities for imaging signalling events at single molecule resolution within intact cells. We use these technologies to study how T cells are activated by presentation of antigens from infectious agents or tumours. We also study the molecular interactions of the tumour suppressor protein, Scribble, using single molecule imaging, to determine how Scribble coordinates cell polarity and cell signalling.
Yassin M and Russell SM (2016). Polarity and asymmetric cell division in the control of lymphocyte fate decisions and function. Curr Opin Immunol. 39: 143-149.
Hawkins E, Oliaro J, Ramsbottom K, Newbold A, Humbert PO, Johnstone RW and Russell S (2016). Scribble acts as an oncogene in Eμ-myc driven lymphoma. Oncogene. 35: 1193-7.
Pham K, Shimoni R, Charnley M, Ludford-Menting MJ, Hawkins, ED, Ramsbottom K, Oliaro J, Izon D, Ting S, Reynolds J, Lythe G, Molina-Paris C, Melichar H, Robey E, Humbert PO, Gu M and Russell SM (2015). Asymmetric cell division during T cell development controls downstream fate. J Cell Biol. 210: 933-50.
Chen Y, Lin H, Ludford-Menting MJ, Gu M and Russell SM (2015). Polarization of excitation light influences molecule counting in single-molecule localization microscopy. Histochem Cell Biol. 143(1):11-9.
Hawkins ED, Oliaro J, Kallies A, Belz GT, Filby A, Hogan T, Haynes N, Ramsbottom K, Van Ham V, Kinwell T, Seddon B, Davies D, Tarlinton D, Lew AM, Humbert PO and Russell SM. Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity (2013). Nature Commun. 4:1801.
Pham K, Shimoni R, Ludford-Menting MJ, Nowell CJ, Lobachevsky P, Bomzon Z, Gu M, Speed TP, McGlade CJ and Russell SM (2013). Divergent lymphocyte signaling revealed by a powerful new tool for analysis of time lapse microscopy. Immunol Cell Biol. 91:70-81.
Oliaro J, Van Ham V, Sacirbegovic F, Pasam A, Bomzon Z, Pham K, Ludford-Menting M, Waterhouse N, Bots M, Hawkins E, Watt S, Cluse L, Clarke C, Izon D, Chang J, Thompson N, Gu M, Johnstone R, Smyth M, Humbert P, Reiner S and Russell SM (2010). Asymmetric Cell Division of T Cells Upon Antigen Presentation Utilizes Multiple Conserved Mechanisms. J Immunol. 185: 367-375.