1.5-year Postdoctoral position available for studying the role of sialic acids in early brain development using brain organoids

Background: 
Protein glycosylation, the process of attaching sugar units to proteins that reside on the surface of cells, plays a crucial role in cell communication and migration, vital for the formation of organs like the brain. A significant distinction between humans and our primate kin is the existence of a sugar molecule known as sialic acids (SA) on the proteins of cell surfaces. Humans, due to a mutation in the CMAH gene (which converts N-acetylneuraminic acid (Neu5Ac) into N-glycolylneuraminic acid (Neu5Gc)), only possess the precursor molecule Neu5Ac. In contrast, greater Apes possess both Neu5Ac and Neu5Gc. This mutation occurred post our common ancestry with chimpanzees. This alteration in SAs has led to changes in proteins that interact with sialic acid and other related proteins. Coupled with other variations in enzymes associated with SA biology between humans and monkeys, these changes could affect brain development and contribute to unique human traits. In our current project, we aim to utilize gene editing technology (CRISPR/Cas9) to alter key genes involved in SA biology in induced pluripotent stem cells (iPSCs). We will then use these modified cells to investigate early brain development in iPSC-derived 3D brain organoids, employing Omics and imaging techniques.

Location of the project:
The project is taking place in the research group of Prof. 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 Prof. Peter Roepstorff and is internationally recognized for their contributions within biological mass spectrometry, proteomics, PTMomics, biomedical research and clinical proteomics. The PRG consist today of a large international research environment with 8 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 Orbitrap Astral and two Bruker TIMS TOF Pro/Ultra2 instruments. 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 have recently sat 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 centered 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 (see link for more information: (https://www.sdu.dk/en/om_sdu/institutter_centre/bmb_biokemi_og_molekylaer_biologi/forskning/forskningsenheder/martinrlarsen).

Qualifications for the candidate
A successful candidate should have a Ph.D. degree in cell biology, molecular biology, glycobiology or proteomics and should be highly motivated and innovative. A candidate must have significant experience in stem cell cultures and preferably stem cell-based 3D cell cultures. Experience in LC-based mass spectrometry of peptides, glycoproteomics or proteomics and microscopy are strong merits. 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: 26 February 2025 at 23:59 hours local Danish time 
Expected starting date: 1 May 2025