Call for applications for a fully financed PhD fellowship
Oncolytic viruses (OVs) represent a promising class of cancer therapeutics that selectively infect and eliminate malignant cells while simultaneously activating antitumor immune responses. Despite encouraging results, many solid tumors remain partially or fully resistant to OV-based therapies, highlighting the need to better understand the cellular mechanisms that govern viral efficacy.
This PhD project will investigate how host chromatin-remodeling factors influence the outcome of oncolytic virotherapy. Building on a genome-wide CRISPR screen performed in lung cancer cells infected with VSVΔ51M - an attenuated, interferon-sensitive mutant of the RNA virus vesicular stomatitis virus widely used in oncolytic virotherapy - SMARCB1 and SMARCA2 were identified as key restriction factors limiting viral activity. Both proteins are central components of the ATP-dependent SWI/SNF chromatin-remodeling complex, which regulates gene expression through nucleosome repositioning. This complex is frequently altered in cancer, with mutations occurring in more than 20% of tumors, and has been implicated in therapy resistance.
While loss or dysregulation of SWI/SNF components enhances the susceptibility of cancer cells to VSV-based oncolytic therapy - likely through impaired interferon responses - emerging data indicate that herpes simplex virus (HSV), including oncolytic variants, exhibits the opposite dependency. In contrast to VSV, HSV appears to rely on intact SWI/SNF function for efficient replication, and disruption of SMARCB1 or SMARCA2 reduces viral propagation.
This project will focus on dissecting the molecular basis of this dependency, with particular emphasis on HSV. The aim is to define how SWI/SNF-mediated chromatin remodeling regulates HSV infection, replication, and spread in cancer cells. You will work closely with experienced researchers in a collaborative and interdisciplinary environment.
The candidate must hold a Master’s degree in molecular biology, molecular medicine, biomedicine, virology, or a related field.
A strong interest in cancer biology, virology, and host–pathogen interactions is essential. Prior experience with molecular biology techniques (e.g. CRISPR/cas9, plaque assay, qPCR, Western blotting), mammalian cell culture and virus infections will be considered an advantage.
Familiarity with antiviral signaling pathways (e.g. interferon responses) and oncolytic viruses is an advantage.
The candidate should have strong analytical skills and an interest in interdisciplinary research combining cancer biology and virology.
Please submit your application via this link. Application deadline is 15 June 2026 at 23:59 CET. Preferred starting date is 1 September 2026.
For information about application requirements and mandatory attachments, please see our application guide.
Please contact Associate professor David Olagnier, olagnier@biomed.au.dk, for more information.
All interested candidates are encouraged to apply, regardless of their personal background. Salary and terms of employment are in accordance with applicable collective agreement.
