Bioinformatic analysis of zebrafish models of Alzheimer's Disease

This project involves the bioinformatic analysis of zebrafish models of Alzheimer's Disease.

Bioinformatic analysis of zebrafish models of Alzheimer's Disease

Bioinformatic analysis of zebrafish models of Alzheimer's Disease.
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Alzheimer's disease is the major form of dementia but its cause is still largely a mystery. However, there are inherited forms of Alzheimer's disease that occur early (before 65 years of age) and are caused by mutations in only a small number of genes.

By analysing what these genes do at a molecular level, we can gain insight into the mechanisms underlying the disease.

Some families are unfortunate to be afflicted by mutations that cause an early onset form of Alzheimer’s disease (before 65 years of age). The disease still takes decades to develop but we do not know what causes it since we cannot take biopsies from living human brains to make detailed molecular analyses. One way around this problem is to engineer the Alzheimer’s disease mutations into a model organism to then study the brains of young adult animals.

The zebrafish is an excellent model for this purpose since mating of a pair of zebrafish can produce a family of over 100 siblings that can then be raised together in the same tank. This reduces genetic and environmental variation and allows more sensitive detection of changes in gene and protein expression.

We are the first researchers to use CRISPR-technologies to engineer Alzheimer’s disease-like mutations into zebrafish. We are analysing the brain transcriptomes from young adult mutant fish and their wild type siblings using RNAseq.

We then compare these transcriptomes to see how gene expression in the mutant brains differs from normal. The functional significance of these differences is then elucidated using a variety of bioinformatics approaches.

This Honours project will involve bioinformatics investigation of our RNAseq data in collaboration with Dr Stephen Pederson at the University of Adelaide’s Bioinformatics Hub.

A student will learn how to process raw RNAseq data and then how to analyse it using the most up-to-date bioinformatics approaches available.

Michael Lardelli

Supervisors

Associate Professor Michael Lardelli

Co-supervisor: Dr Morgan Newman

Research area: Alzheimer's Disease Genetics Laboratory

Recommended honours enrolment: Honours in Molecular and Biomedical Science

Tagged in Honours projects - Molecular and biomedical science, Honours projects - Michael Lardelli, Honours projects - Morgan Newman, Honours projects - Molecular and biomedical science: Genetics