Correct protein folding is essential for the functioning of living cells and organisms. Many human diseases are associated with protein misfolding and aggregation, which lead to toxicity and cell death by largely unknown mechanisms. The Sinnige lab is a new team within the section Membrane Biochemistry & Biophysics at the Bijvoet Centre for Biomolecular Research, and is currently seeking two highly motivated and enthusiastic PhD candidates to investigate the molecular mechanisms of protein aggregation in vivo using C. elegans as a model organism.

Project 1 explores the fundamental biophysical properties of aggregation-prone proteins within a living organism. You will make use of C. elegans expressing fluorescently labelled polyglutamine, which is related to Huntington’s disease, and track the kinetics of protein aggregation by microscopy as the animal is ageing. Quantitative analysis of the aggregation kinetics in different genetic backgrounds will allow you to address key questions in the field regarding the mechanisms of protein aggregation in a living animal. For example, why are some cell types more vulnerable to protein aggregation than others? What causes molecular chaperones to fail in preventing protein aggregation?

Project 2 addresses the mechanisms of protein aggregation in relation to biological membranes. A variety of disease-associated peptides and proteins are known to interact with cellular membranes, which play an important yet poorly understood role in the aggregation mechanism. You will use existing transgenic C. elegans models, and create novel ones to uncover the features of membrane-associated protein aggregation using fluorescence microscopy and biochemical methods. The use of C. elegans furthermore allows you to observe the behaviour of the animals (e.g. movement, response to chemicals) to assess the toxicity caused by protein aggregation. You will also use these approaches to test small molecules that have the potential to interfere with protein-membrane interactions and the aggregation process, thereby reducing the toxic effects.

We are looking for two colleagues who are creative and persistent, and have:

• a MSc degree in biomolecular sciences or a related discipline;
• experience with sterile microbiological work or cell culture;
• the ability to work independently;
• affinity with learning new techniques and working in an interdisciplinary environment;
• good writing and presenting skills in English.

Experience with C. elegans is an advantage, but not required.

• an exciting opportunity to be part of a young, interdisciplinary research team;
• a full-time position for 4 years;
• a full-time gross salary that starts at €2,395 and increases to €3,061 per month in the fourth year (scale P of the Collective Labour Agreement Dutch Universities (cao));
• benefits including 8% holiday bonus and 8.3% end-of-year bonus;
• a pension scheme, partially paid parental leave, and flexible employment conditions based on the Collective Labour Agreement Dutch Universities.

In addition to the employment conditions laid down in the cao for Dutch Universities, Utrecht University has a number of its own arrangements. For example, there are agreements on professional development, leave arrangements and sports. We also give you the opportunity to expand your terms of employment yourself via the Employment Conditions Selection Model. This is how we like to encourage you to continue to grow.

More information about working at the Faculty of Science can be found here.

Membrane Biochemistry and Biophysics is an international and interdisciplinary research group that focuses on topics including protein-lipid interactions, the development of novel antibiotics, and protein and lipid homeostasis. The range of biological model systems available within the group has recently been expanded to include the nematode C. elegans. The Sinnige lab uses transgenic worms to study the misfolding and aggregation of proteins involved in e.g. Huntington’s disease and type II diabetes. In collaboration with other groups within the Bijvoet Centre for Biomolecular Research, we aim to apply biophysical and structural biology methods to examine protein misfolding and its relation to ageing and disease in molecular detail.

At the Faculty of Science there are 6 departments to make a fundamental connection with: Biology, Chemistry, Information and Computing Sciences, Mathematics, Pharmaceutical Sciences and Physics. Each of these is made up of distinct institutes which work together to focus on answering some of humanity’s most pressing problems. More fundamental still are the individual research groups – the building blocks of our ambitious scientific projects.

Utrecht University is a friendly and ambitious university at the heart of an ancient city. We love to welcome new scientists to our city – a thriving cultural hub that is consistently rated as one of the world’s happiest cities. We are renowned for our innovative interdisciplinary research and our emphasis on inspirational research and excellent education. We are equally well-known for our familiar atmosphere and the can-do mentality of our people. This lively and inspiring academic environment attracts Professors, Researchers and PhD candidates from all over the globe, making both the university and the Faculty of Science a vibrant international community and wonderfully diverse.