Novel disease genes in brain development and decline

Overview

The Rare Disorder Genetics / Bicknell lab is interested in characterising novel genetic syndromes, with three core motivations:

• The difference we can make to families with rare disorders, through providing them with more information
• The awesome power of genetic alterations to impact development and functioning
• The insight we can gain into organism biology, through a Mendelian variant perspective

We harness exome and genome sequencing to study a variety of disorders, with a focus on how our brains and bodies grow. We undertake research using samples mainly from New Zealand families, but we also get samples from our international collaborations.

We get particularly excited studying the fundamental aspects of cell functioning and their role in disease, and have a current focus on DNA replication, splicing, chromatin remodelling and RNA-binding proteins.

This PhD will use a mix of molecular biology and bioinformatics to explore the contribution of two RNA-binding proteins to both a monogenic genetic disorder affecting neurodevelopment, and as a risk factor for later onset aging-related neurological disorders.

To investigate these proteins in the lab, the project will employ common protein approaches such as stability assays, protein interactions (co-immunoprecipitations), and RNA binding efficiency.

To explore the contribution as a risk factor, the project will make use of the UK biobank (and potentially other biobanks) to look for enrichment of predicted damaging variants in these genes in people with features of aging-related neurological disorders.

Principal Investigator

Associate Professor Louise Bicknell.

I have a very strong track record in human disease genetics, and am well-supported for our research with funding and collaborations. My passion and enthusiasm for our research underpins a fantastic, closely-knit team of researchers and we are proud to generate exciting, robust results that have a positive impact on families. We value strong communication, collegiality and inclusivity in our lab.

Students are encouraged to develop their own niche to their project – supporting career development while undertaking excellent science.

The successful candidate will have obtained a BSc(Hons) or MSc with strong academic excellence and lab research experience. Knowledge of the following areas would be desirable: genetics, molecular biology and bioinformatics, however personal attributes are just as important as the right skillset.

The prospective candidate will need to obtain a University of Otago PhD scholarship (which are highly competitive – minimum GPA 8 out of 9). Associate Professor Bicknell will provide significant support with this application.

For international students, multiple publications are likely to be required for a strong scholarship application. Please apply to Associate Professor Bicknell with your CV (including three references), the transcripts for academic qualifications and a cover letter outlining your interest and career goals, relevant to this project and joining the Rare Disorder Genetics lab.