Genetics and Epigenetics Laboratory

Lab head: A/Prof John Kwok
Location: Brain and Mind Centre

Using high-throughput cellular assays to screen dementia gene variants

Primary supervisor: Carol Dobson-Stone

Mutations in several genes cause inherited forms of dementia, such as autosomal dominant Alzheimer’s disease and frontotemporal dementia. Recent advances in DNA sequencing technology make it a simple prospect to sequence all of these genes in any person with an inherited dementia. What is significantly less straightforward is how to interpret novel variants in these genes. Traditional cellular assays testing the effect of such variants on pathological pathways are time consuming and examine only one or a few variants at a time. This means that even for established disease genes, many variants are simply classified as ‘variants of unknown significance’ (VUS) without being investigated further. This uncertainty can cause confusion, may delay accurate diagnosis of the underlying mechanism for the dementia symptoms and hinders family planning decisions for relatives who don’t know their carrier status. Our lab is developing an efficient and systematic battery of cellular assays to assess the pathogenicity of multiple dementia gene variants at once. The aim of this honours project is to help develop one or more of these assays and use them to screen VUS of a known dementia gene, to determine which variants are likely to be pathogenic (disease-causing) and which are benign.


Acquired skills and techniques


• Experimental design

• Molecular biology techniques (e.g., polymerase chain reaction (PCR) analysis, molecular cloning, DNA sequencing, cell culture)

• Immunocytochemical analysis

• Confocal microscopy

• Statistical analysis and interpretation of results


 This project would suit an organised student who is able to work carefully and independently and has an eye for detail. Prior knowledge of molecular biology/genetics is preferred but not essential.

Discipline: Pathology
Keywords: Dementia, Alzheimer's disease, Genetics