We are looking for a PhD candidate to perform scientific research in the area of “Intestinal response to bacterial pathogens”. The intestinal microbiota is essential for human health, but can also cause inflammation, for example in patients that suffer from ulcerative colitis or Crohn’s disease. We want to understand how pathobionts or pathogens cause inflammation or epithelial invasion. Interactions between microbiota and the host take place in the mucus layer. Transmembrane mucins are receptor-like glycosylated proteins expressed on the apical surface of intestinal epithelial cells. These mucins can have barrier functions, be utilized by pathogens for invasion and initiate signaling events. For example, we published that the transmembrane mucin MUC1 can be hijacked by Salmonella and utilized for apical invasion of intestinal epithelial cells (Li et al, PLoS Pathogens; PMC6375660). 
The goal of this PhD project is to investigate the downstream signaling events that are initiated by pathobiont or pathogen binding to transmembrane mucins. These pathways can include epithelial innate immune responses, actin rearrangements and endocytosis, nuclear localization of the mucin cytoplasmic tail, regulation of cellular junctions, cellular migration or apoptosis. To characterize these signaling pathway in intestinal epithelial cells, you will make use of a wide variety of molecular and cell biological techniques (e.g. labeling and immunoprecipitations, mass spec identification, microscopy, reporter assays, CRISPR/Cas9 and immunological assays). In addition, you need to master microbiology techniques to be able to perform infection assays. Your findings will be published in peer-reviewed journals and you will present your work in the department and at international conferences. Depending on your experience, you may be responsible for the daily supervision of MSc students.

Techniques:

• cell culture of epithelial cell lines, generation of knockout and overexpression cell lines;
• molecular techniques such as protein expression, immunoprecipitation, western blotting and cloning;
• cell biological assays including infection and reporter assays, migration and wound healing assays, immunofluorescence and confocal microscopy;
• microbiological techniques such as bacterial culturing and generation of knockouts.

This PhD position is part of an ERC project so you will be part of a team of 4 scientists. The Infection Biology group has a strong focus on mucosal host-microbe interactions and the underlying molecular mechanisms. We are part of the division Infectious Diseases and Immunology in the Department of Biomolecular Health Sciences of the Faculty of Veterinary Medicine.

• a highly motivated curiosity-driven individual with a passion for cell biology and host-microbe interactions;
• experience with molecular and cell biological techniques, ideally some of the techniques listed. Please specifically describe your experience and motivation in your cover letter;
• a MSc degree in infection and immunity, cell biology, microbiology, immunology or equivalent.

We offer a temporary position (1.0 FTE) for a period of four years. The gross salary - depending on previous qualifications and experience  - ranges between €2,395 and €3,061 (scale P according to the Collective Labour Agreement Dutch Universities) per month for a full-time employment. Salaries are supplemented with a holiday bonus of 8% and a year-end bonus of 8.3% per year. In addition, Utrecht University offers excellent secondary conditions, including an attractive retirement scheme, (partly paid) parental leave, collective insurance schemes and flexible employment conditions (multiple choice model). More information about working at Utrecht University can be found here.

A better future for everyone. This ambition motivates our scientists in executing their leading research and inspiring teaching. At Utrecht University, the various disciplines collaborate intensively towards major societal themes. Our focus is on Dynamics of Youth, Institutions for Open Societies, Life Sciences and Sustainability.

The Faculty of Veterinary Medicine has a unique position in the Netherlands. Not only is this the only institution where Veterinarians are trained, Researchers are also working together on innovative scientific research. In addition, the faculty provides specialist clinical care in the largest academic veterinary hospital in Europe. Thanks to this position, the Faculty of Veterinary Medicine is a point of contact for all veterinary matters, both nationally and increasingly internationally. The faculty employs approximately 900 Veterinarians, Scientists and support staff and counts 1,500 students.