Readvertisement: Dissecting O-GlcNAc transferase intellectual disability

Website Aarhus University

Last Day to Apply: 1 August 2024

Project description:
Early onset intellectual disability (ID) is characterised by limitations in cognitive function and adaptive behaviour. Protein O-GlcNAcylation, catalysed by O-GlcNAc transferase (OGT), is a post-translational modification that is indispensable for embryogenesis. Recently we have discovered families where OGT missense mutations segregate with syndromic ID (“OGT-CDG”) including developmental delay, behavioural problems, ataxia, clinodactyly and microcephaly [PNAS 2019, EJHG 2020].

Several PhD positions, funded by Novo Nordisk Foundation Laureate and Villum Investigator awards, are now available to join a multidisciplinary and multi-cultural lab on our journey to dissect this disease. Our long-term vision is to uncover the O-GlcNAc-dependent biological mechanisms that are affected in these patients and, in the longer term, use these findings to inform and develop treatment strategies.

Projects are available in three areas:
1) Introduce OGT-CDG mutations in mESCs, Drosophila and mice to quantify biochemical, cellular, structural and behavioural phenotypes, and modulate these using genetic, chemical and metabolic approaches [see DMM, 2023 and PLOS Genetics, 2022 as examples].

2) Use these model systems to uncover candidate O-GlcNAc proteins that link to OGT-CDG phenotypes, using a combination of proteomics, transcriptomics, bioinformatics and genetic screens [initial work accessible on bioRxiv].

3) Dissect the biological functions and molecular consequences of site-specific O-GlcNAcylation, including a new method to site-specifically increase O-GlcNAc stoichiometry in vivo [see Gorelik et al, NSMB, 2019].

We are seeking self-motivated students that are keen to explore their own ideas within this space. You will need to have a 2-year masters degree in the area of molecular neuroscience in the broadest sense, including a peer-reviewed publication. There may be opportunities for temporary employment before committing to a PhD. You are strongly encouraged to contact Daan (daan@mbg.au.dk) before submitting a formal application.

For technical reasons, you must upload a project description. When – as here – you apply for a specific project, please simply copy the project description above, and upload it as a PDF in the application. If you wish to, you can indicate an URL where further information can be found.

Qualifications and specific competences:
Applicants must have a master’s degree and at least one first author publication in a peer reviewed journal. As a multi-disciplinary lab, we accepted applicants from any relevant field. They must be able to work very independently, be able to write their own project proposal in the first few months and be entirely self-motivated and hard working. Candidates are very strongly advised to informally contact the PI, Daan van Aalten (daan@mbg.au.dk) before submitting a formal application.

Place of employment and place of work:
The place of employment is Aarhus University, and the place of work is Department of Molecular Biology and Genetics, Universitetsbyen 81, 8000 Aarhus C, Denmark.

Contacts:
Applicants seeking further information for this project are invited to contact: Professor Daan van Aalten, daan@mbg.au.dk.

How to apply:
For information about application requirements and mandatory attachments, please see the application guide Please read the Application guide thoroughly before applying.
When ready to apply, go to https://phd.nat.au.dk/for-applicants/apply-here/ (Note, the online application system opens 1 June 2024)
1. Choose August 2024 Call with deadline 1 August 2024 at 23:59 CET.
2. You will be directed to the call and must choose the programme “Molecular Biology and Genetics”.
3. In the boxed named “Study”: In the dropdown menu, please choose: “Readvertisement: Dissecting O-GlcNAc transferase intellectual disability (RDOtid)”

Please note:
The programme committee may request further information or invite the applicant to attend an interview.
At the Faculty of Natural Science at Aarhus University, we strive to support our scientific staff in their career development. We focus on competency development and career clarification and want to make your opportunities transparent. On https://nat.au.dk/en/about-the-faculty/career you can find information on all types of scientific positions, as well as the entry criteria we use when assessing candidates. You can also read more about how we can assist you in your career planning and development.

To apply for this job please visit phd.nat.au.dk.

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