PhD position in integrative structural biology of enterovirus 2C proteins (1.0 FTE)

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 .