Discovered the expression of an unusual splice isoform of CDC42 in cytotoxic T lymphocytes (CTL). Elucidated the role of this protein isoform in activating dynein-mediated transport of secretory lysosomes towards the immune synapse for CTL-mediated killing. Manuscript under review at Journal of Cell Biology and is available upon request.
Discovered potent transcriptional adaptation (TA) in CTLs in response to CRISPR/Cas9-mediated deletion of Cdc42. Characterised the molecular pathways leading to enhanced CTL function after TA. Publication.
Collaborations: Carsten Speckmann (University of Freiburg, Germany), Doreen Cantrell (University of Dundee, Scotland)
Optimised novel actin conformation probes for use in CTLs. Optimised traction force microscopy for CTLs. Discovered spatiotemporal correlation between distinct F-actin conformations and force production by CTLs. Manuscript submitted to Nature Communications. Preprint.
Collaborations: Dan Fletcher (UC Berkeley, USA), Anna Lippert (University of Würzburg, Germany), Alex Winkel (University of Cambridge, UK)
Discovered a unique cellular phenotype in the CTLs from patients with a novel ∆RAB27A mutation, whereby CTL function is maintained despite loss of canonical granzyme/perforin-mediated killing pathway. These data formed the basis for grant applications for future work proposing cellular phenotyping of patients with inborn errors in immunity to predict future immunodeficiency.
Determined the impact of novel ITPR3 mutations on calcium homeostasis and nuclear translocation of transcription factors in patient CTLs. Publication.
MRes Rotation III
Literature review discussing the potential for imaging modality to bias results regarding the localisation and dynamics of the T cell receptor, particularly in the resting T cell. Publication.