Mice, organoids and single cells: computational methods for cancer treatment

2020-03-10T03:52:49Z (GMT) by Elizabeth Permina
Hereditary Diffuse Gastric Cancer (HDGC) affects hundreds of people in New Zealand, many from Māori families. An inherited mutation in the E-cadherin gene (CDH1) is a strong driver of HDGC, affecting individuals as young as 15 years old. A promising way of combatting HDGC involves finding a synthetic lethal (SL) partner to the HDGC-defining gene, CDH1. Synthetic lethality is defined as a specific relationship between two genes where a loss of one is tolerated by the cell but the loss of both is lethal. An innovative way of mixing computational approaches with experimental data offers a method of identifying a range of prospective drug targets and treatments. Generation of mouse gastric organoids (simplified versions of a mouse stomach produced from mouse stem cells with a micro-anatomy that is close to that of a real stomach) with and without CDH1 loss, provide a realistic model for HDGC, and single-cell RNA sequencing (scRNA-seq) then provides whole-transcriptome data for these organoid samples. Here I will present an analysis of the organoid scRNA-seq data, utilizing linkage to existing SL gene and pathway data (including siRNA studies done previously in our lab) as well as integration of publicly accessible data sets derived from patient tumours.

ABOUT THE AUTHOR(S)
Elizabeth Permina is a Postdoctoral Research Fellow working on the HRC funded research programme “Reducing the burden of gastric cancer in New Zealand”, based in the Centre for Translational Cancer Research at the University of Otago, Dunedin.

Tom Brew is a PhD student in Biochemistry, with research focused on developing novel approaches to treating hereditary diffuse gastric cancer.

Associate Professor Mik Black is a Principal Investigator in the Centre for Translational Cancer Research at the University of Otago, and the bioinformatics lead for Genomics Aotearoa, a national initiative for developing genomics and bioinformatics capability in New Zealand. His research focuses on the development and application of statistical and bioinformatics methodology to problems in human health, with a particular focus on cancer.

Professor Parry Guilford is a Principal Investigator in the Centre for Translational Cancer Research at the University of Otago, whose research focuses on the role played by the gene E-cadherin in the development and progression of hereditary diffuse gastric cancer. He is also a co-founder and Chief Scientific Officer of Pacific Edge Ltd.

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