Institute for Plant Cell Biology and Biotechnology, Heinrich-Heine University of Düsseldorf https://www.plant-cell.hhu.de/en/.
Decoding Extracellular Glycan O-Acetylation: From Fungi to Plants and Beyond
Glycan O-acetylation is a chemically subtle yet biologically impactful modification. Pathogenic bacteria O-acetylate their surface glycans to evade immune detection. In plants, reduced O-acetylation of cell wall glycans is associated with altered responses to environmental stress, while in human cells it causes increased susceptibility to viral infections, including HIV and influenza. Despite its importance, O-acetylation of extracellular glycans remains a largely overlooked layer of glycan regulation.
Our lab aims to address this gap in knowledge. We have discovered a fungal protein, CAS1, that mediates O-acetylation of extracellular glycans. When CAS1 is knocked out in yeast using CRISPR, O-acetylation is lost. Remarkably, when CAS1 is expressed in yeast species that do not normally O-acetylate their cell walls, they begin to produce O-acetylated glycans. These results suggest that CAS1 integrates both transport and transfer functions within a single polypeptide, and reveal a striking functional conservation across fungi and plants, pointing towards a shared and ancient molecular mechanism that may extend even to bacterial and human systems.
This PhD project aims to dissect the structure-function relationships of CAS1 and the broader O-acetylation machinery, combining tools from biochemistry, structural biology, genetics and glycoscience.
Decoding Extracellular Glycan O-Acetylation: From Fungi to Plants and Beyond
Glycan O-acetylation is a chemically subtle yet biologically impactful modification. Pathogenic bacteria O-acetylate their surface glycans to evade immune detection. In plants, reduced O-acetylation of cell wall glycans is associated with altered responses to environmental stress, while in human cells it causes increased susceptibility to viral infections, including HIV and influenza. Despite its importance, O-acetylation of extracellular glycans remains a largely overlooked layer of glycan regulation.
Our lab aims to address this gap in knowledge. We have discovered a fungal protein, CAS1, that mediates O-acetylation of extracellular glycans. When CAS1 is knocked out in yeast using CRISPR, O-acetylation is lost. Remarkably, when CAS1 is expressed in yeast species that do not normally O-acetylate their cell walls, they begin to produce O-acetylated glycans. These results suggest that CAS1 integrates both transport and transfer functions within a single polypeptide, and reveal a striking functional conservation across fungi and plants, pointing towards a shared and ancient molecular mechanism that may extend even to bacterial and human systems.
This PhD project aims to dissect the structure-function relationships of CAS1 and the broader O-acetylation machinery, combining tools from biochemistry, structural biology, genetics and glycoscience.
PhD Position (w/m/d, 65% EG13 TV-L, 3 years)
Activities and responsibilities
- Identify catalytic residues using structure-guided mutagenesis, topology prediction, and complementation studies in yeast.
- Produce CAS1 variants and characterize their enzymatic activity in vitro.
- Investigate yeast mutants to uncover new components of the machinery.
- Translate mechanistic insights into plant systems, exploring potential applications in biotechnology or plant stress responses.
- Teaching responsibilities (2SWS)
- Produce CAS1 variants and characterize their enzymatic activity in vitro.
- Investigate yeast mutants to uncover new components of the machinery.
- Translate mechanistic insights into plant systems, exploring potential applications in biotechnology or plant stress responses.
- Teaching responsibilities (2SWS)
Qualification profile
• MSc in biology, biochemistry
• Strong background in molecular biology, genetics, and/or analytical techniques
• Strong organizational, solution-focused, and team-working skills
• Demonstrated scientific writing experience
• Excellent English communication skills
• Strong background in molecular biology, genetics, and/or analytical techniques
• Strong organizational, solution-focused, and team-working skills
• Demonstrated scientific writing experience
• Excellent English communication skills
Applicants should submit a single pdf-file containing a letter of motivation, a resume including a summary of research experience, copies of transcripts and certificates and contact information of 2-3 references. The application should be sent via e-mail to Prof. Dr. Markus Pauly (email)
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