Postdoc Position to Study Early Brain Development Using Brain Organoids, CRISPR/Cas9 Gene Editing and Glycoproteomics

A two-year postdoctoral position is available in a larger project aiming at investigating the role of sialic acids in early brain development using brain organoids at Department of Biochemistry and Molecular Biology.

Background:
Protein glycosylation, addition of sugar units to proteins that are placed on the cell surface, is important for communication between cells and cell migration, mechanisms essential for development of organs, such as the brain. A big difference between humans and our primate relatives is the presence of the sugar molecule called sialic acids (SA) on cell surface proteins. Due to a mutation in the CMAH gene (an enzyme that convert N-acetylneuraminic acid (Neu5Ac) to N-glycolylneuraminic acid (Neu5Gc)) that took place in humans after the common ancestor with the chimpanzee, humans have the precursor molecule Neu5Ac whereas greater apes have both Neu5Ac and Neu5Gc. This change in SAs has resulted in changes in sialic acid binding proteins and other proteins related to the biology of sialic acids. This, together with other changes in enzymes related with SA biology between human and monkeys could have an influence on the development of the brain and participate in human-specific features. In the present project we will use gene editing (CRISPR/Cas9) to modulate important genes in SA biology in induced pluripotent stem cells (iPSCs) and use these to study the early brain development in iPSC-derived 3D brain organoids using Omics and imaging technology.

Location of the project:
The project is taking place in the research group of Professor Martin R. Larsen, Department of Biochemistry and Molecular Biology at the University of Southern Denmark.

The Larsen research group is part of the Protein Research Group (PRG) at the University of Southern Denmark (sdu) in Odense, Denmark. Odense is located only one hour from the main capital of Denmark, Copenhagen. The PRG was founded 48 years ago by the recognized protein and biological mass spectrometry researcher Professor Peter Roepstorff and is internationally recognized for their contributions within biological mass spectrometry, proteomics, PTMomics, biomedical research and clinical proteomics. The PRG consists today of a large international research environment with eight individual research groups and more than 60 scientists, postdocs and students who share laboratory facilities and research environment. The PRG has a fantastic student environment with many multicultural inputs.

The PRG has the newest mass spectrometers for biological mass spectrometry applications including one Orbitrap Lumos Tribrid, one Orbitrap Eclipse Tribrid, two Orbitrap Exploris480, two Q-Exactive HF and one Bruker TIMS TOF Pro. In addition, the PRG has a large fully equipped protein chemistry/proteomics laboratory, cell laboratory facilities and bioinformatics that will be available for the present project. The Larsen Group has recently set up the 3D brain organoid technology to study early brain development in health and diseases.

The Larsen group has for the past 20 years developed many methods for assessment of PTMs in proteomics, including the Titanium Dioxide method (Larsen MR et al., Mol. Cell. Proteomics 2005) used by many research groups worldwide for isolation of phosphorylated peptides for characterization of signal transduction pathways in mammalian systems. Furthermore we have developed methods to access sialylated N-linked glycosylation, Cysteine modifications, lysine acetylation and O-GlcNAcylation. The research focus of the Larsen group is centred around investigation of the role of these PTMs in system biology and biomedicine and on the development of new innovative methods for assessment of other PTMs in biological samples. The Larsen group has a significant amount of national and international collaborations and is publishing in higher ranging journals.

Qualifications of the candidate
A successful candidate should have a PhD degree in cell biology, molecular biology, glycobiology or proteomics and should be highly motivated and innovative. A candidate must have significant experience in LC-based mass spectrometry of peptides, glycoproteomics or proteomics. Experience in CRISPR/Cas9 gene editing and stem cells is a strong merit. Excellent communication and writing skills and an ability to interact socially and scientifically with other laboratory members and collaborators are essential. Previous postdoc experience and a strong publication record are also strong merits.

Application deadline: 1 June 2023.
Expected starting date: Soon after deadline.

For further information please contact Professor Martin R. Larsen, PhD, e-mail: [email protected].

Application, salary etc.
The successful applicant will be employed in accordance with the agreement between the Ministry of Finance and AC (the Danish Confederation of Professional Associations). Please check links for more information on salary and taxation.

The application must include the following:
• A curriculum vitae including information on previous employment.
• A full list of publications stating the scientific publications on which the applicant wishes to rely.

Shortlisting may be used in the assessment process.

Incomplete applications and applications received after the deadline will neither be considered nor evaluated.

To qualify you must have passed a PhD or equivalent. Applications will be assessed by an expert assessor/committee. Applicants will be informed of their assessment by the university.

The University wishes our staff to reflect the diversity of society and thus welcomes applications from all qualified candidates regardless of personal background.

Applications must be submitted electronically using the link "Apply online". Attached files must be in Adobe PDF or Word format. Each box can only contain a single file of max. 10 Mb. We strongly recommend that you read How to apply before you apply.

Further information for international applicants about entering and working in Denmark.