We offer a position for a talented PhD candidate to study the function and antiviral inhibition of enterovirus 2C proteins using an integrative structural biology approach.
Your PhD research will be embedded in the Department of Biomolecular Health Sciences within the Faculty of Veterinary Medicine. You will be supervised and coached in your development by Dr. Daniel Hurdiss and Prof. Frank van Kuppeveld (also promotor) and will collaborate closely with Dr. Joost Snijder, whose group is located within the Biomolecular Mass Spectrometry and Proteomics group at Utrecht University.

The genus Enterovirus comprises many clinically relevant human pathogens, such as the poliovirus, coxsackievirus, rhinovirus and emerging viruses such as EV-A71 and EV-D68. Diseases associated with these pathogens range from mild illnesses to debilitating, and occasionally life-threatening conditions such as meningitis, encephalitis, and acute flaccid paralysis. Young children are most at risk of developing severe illness. There is an urgent and unmet need for effective broad-spectrum antiviral drugs.

The enterovirus 2C protein is a particularly attractive target for broad-spectrum antiviral development due to its functional indispensability and high sequence conservation. The 2C protein is a hexameric AAA+ ATPase with many proposed functions in the virus lifecycle, including viral RNA replication (through its helicase activity), formation of replication organelles, and genome encapsidation. However, the molecular mechanisms by which 2C carries out these diverse functions are not understood.

In this position you will develop a set of enzymatically active 2C hexamers from clinically relevant enterovirus species for high-resolution structural analysis, using state-of-the-art cryo-electron microscopy and mass spectrometry techniques, in conjunction with functional biochemical as well as molecular virological experiments. You will elucidate the role 2C plays in genome replication and encapsidation, and how 2C-targeting compounds perturb these functions. For more details, see our recent preprint.

You have:

• a MSc degree in the area of molecular life sciences, preferably (bio)chemistry or biology;
• experience with molecular biology, protein expression and purification. Virology, cryo-electron microscopy and/or mass spectrometry is a plus;
• good organizational skills are a must because you will be working on multiple collaborative sub-projects simultaneously;
• as the Virology Section provides an international research environment, you should have good verbal and written communication skills in English.

You will be offered a temporary position (1.0 FTE) for a period of four years The gross salary ranges between €2,395 in the first year and €3,061 in the fourth year of employment (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 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, but is also where Researchers are 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.

The Virology Section of the Department of Biomolecular Health Sciences of the Faculty of Veterinary Medicine studies the interaction between viruses and their hosts at molecular/cell biological level as well as at the level of the organism. Ultimately, we strive to translate the knowledge obtained into the development of novel vaccines, antiviral therapies, and diagnostic tools.