Current Bioinformatics Seminar
Time: 11AM Tuesdays.
Venue: Davis Auditorium and Online
2 September 2025
Immuno-oncology target discovery through CRISPR screening
Joe CursonsAudax Biosciences
Natural killer cells and T cells are important immune effectors with the ability to directly kill tumour cells. A key regulator of NK cell function/survival and tissue-residency programs in T cells is the cytokine interleukin-15 (IL-15). Using genome-wide CRISPR screens within an NK cell line and targeted sub-library screens within primary human NK cells we identified the cullin-5 RING ligase (CRL5) ubiquitination complex as the primary regulator of IL-15 receptor levels in NK cells. Knockout of individual CRL5 complex members was sufficient to improve surface IL‑15R expression and enhance NK cell and chimeric antigen receptor (CAR)-NK cell anti-tumour function across a range of contexts. In this talk I will outline the rationale and approach taken to identify these novel immuno‑oncology drug targets, with a focus on the computational tools and databases that supported the discovery process. I will also describe some of the principles that help guide the design, execution and analysis of CRISPR screens in different contexts. (This talk will be very similar to my presentation at Cancer Bioinformatics Australia in June and it will cover data from our recent publication in Cancer Cell: Enhancing anti-tumor immunity of natural killer cells through targeting IL-15R signaling)