Summary
This project aims to characterize the role of LDL related receptor 1 (Lrp1) as a host entry factor for multiple bunyaviruses, including Rift Valley Fever virus, Oropouche virus, and La Crosse virus, to identify novel targets for therapeutic development.
What they want
The work will characterize the importance of Lrp1 for the entry of multiple bunyaviruses, define the molecular mechanisms involved, and validate its significance both in vitro and in vivo. This will build upon existing preliminary data from genomic screens, in vitro validation in Lrp1 sufficient and deficient cells, transcomplementation studies, direct interaction studies (e.g., RVFV glycoprotein Gn in vitro), inhibition of Lrp1 by endogenous ligands in vitro across multiple cell lines, and in vivo data demonstrating Lrp1's importance for viral tropism and disease in mice.
Deliverables
- Validation of Lrp1 as a pan-bunyavirus entry factor
- Identification of novel targets for therapeutic development
Technical requirements
- Genomic screening
- In vitro validation in Lrp1 sufficient and deficient cells
- Transcomplementation studies
- Direct interaction studies (e.g., RVFV glycoprotein Gn in vitro)
- Inhibition of Lrp1 by endogenous ligands in vitro in multiple cell lines from evolutionarily distinct hosts
- In vivo studies in mice to demonstrate viral tropism and disease importance
Key personnel
- Investigators with expertise in biochemistry
- Investigators with expertise in viral pathogenesis
- Investigators with expertise in immunology
- Investigators with expertise in proteomics
- Investigators with expertise in structural biology
- Investigators with expertise in virology
