Structure and native functionality of the glycoproteins presented by zoonotic bornaviruses

Bornaviruses constitute a group of under-characterised animal-borne RNA viruses that utilise a range of mammalian hosts as reservoirs. In recent years, an increasing number of bornavirus spillover events have occurred, causing hospitalisations and fatalities. The growing biomedical impact of bornaviruses, combined with the absence of effective therapeutics, underscores the importance of characterising these understudied emerging pathogens.

The bornavirus glycoprotein (BorV-G) is responsible for facilitating host cell entry and is a primary target for vaccine and antiviral development. However, the lack of detailed information about BorV-G structure, receptor usage, and antigenicity limits our

understanding of the molecular determinants of bornaviral host tropism and the sites of vulnerability targeted by neutralising antibodies. In this doctoral research project, the student will employ an integrative structural and functional approach to elucidate molecular-level details of BorV-G architecture and host interactions. The student will receive comprehensive training in state-of-the-art techniques in structural and molecular biology including mammalian protein production, in vitro assays, X-ray crystallography, cryo-EM, cryo-CLEM, cryo-ET, and subtomogram averaging. This work will reveal molecularlevel insights into BorV-G-driven pathobiology.