Mice_organoids_and_single_cells-computational_methods_for_cancer_treatment.pdf (1.49 MB)
Download fileMice, organoids and single cells: computational methods for cancer treatment
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posted on 2020-03-10, 03:52 authored by Elizabeth PerminaHereditary 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.