WEHI Bioinformatics and Computational Biology Special Seminar hosted by Drs James Fu and Mengbo Li

Joe Cursons
Audax Biosciences

 

Immuno-oncology target discovery through CRISPR screening

Davis Auditorium

Join via ZOOM

Including Q&A session

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).

Joe completed his undergraduate degree and PhD in biomedical engineering at the University of Auckland. In his first post-doctoral position with Edmund Crampin at the University of Melbourne, Joe collaborated with the EMPathy consortium to study epithelial-mesenchymal plasticity (EMP) in breast cancer. He next moved to lab of Melissa Davis in the Walter and Eliza Hall Institute Bioinformatics Division, continuing a project on micro-RNA regulation of EMP, and working with the Cancer Therapeutics CRC on their preclinical PRMT5 inhibitor and KAT6A/B inhibitor currently in clinical trials with Pfizer. Finding industry collaboration to be very rewarding, Joe joined the biotechnology startup oNKo-innate – now Audax Biosciences – in early 2019, where he currently leads a small bioinformatics and computational biology team to support target discovery, product development and other research activities.

All welcome!