Dengue haemorrhage: a novel role for perivascular cells
Dengue fever poses a major global public health threat and severe cases are on the rise. While severe dengue cases are relatively rare, the associated haemorrhage complications can be fatal if left untreated. To date, there are no diagnostic tools to determine which patients will go on to develop severe dengue. This studentship will focus on understanding the development of dengue haemorrhagic fever from a vascular biology point of view, with a specific focus on perivascular cells.
Start date1 October 2021
DurationStandard project duration is 4 years.
Stipend is set at UKRI rates and includes full tuition fee waiver for EU/UK students
Funding sourceThe University of Surrey, Project-led Studentship Award.
Dengue is the most significant arthropod-borne disease of humans, with 40% of the global population at risk of infection and an annual incidence of ~100 million symptomatic infections. There is a lack of specific treatments or efficacious vaccines. Severe dengue is characterised by haemorrhage and plasma leakage, due to blood vessel failure. Small blood vessels are composed of two cell types: endothelial cells and pericytes. Pericytes are crucial in regulating blood vessel permeability and their dysfunction characterises other haemorrhagic pathologies, such as diabetes retinopathy. Despite their relevance in maintaining vessel integrity, very little is known on the role of pericytes in dengue viral infection. A recent paper by Dr Campagnolo’s group (primary supervisor) identified a critical role for pericytes in mediating the haemorrhagic response to the secreted dengue virus protein NS1. In this project, the student will investigate the viral serotype-specificity and organ-specificity of the effect of NS1 on pericytes using several in vitro 3D co-culture systems based on human primary vascular cells. The project will also establish the potential molecular players in the disrupted endothelial/pericyte interaction using -omics approaches and genetic/pharmacological inhibitors. Depending on progress and the candidate’s interest, there is an opportunity to receive training in virology techniques up to CL3 level, through a collaboration with Dr Kevin Maringer at the Pirbright Institute. The findings arising from this studentship will help toward the development of new prognostic and diagnostic tests to predict the severity of dengue disease in patients and the identification of new druggable pathways
A Critical Role for Perivascular Cells in Amplifying Vascular Leakage Induced by Dengue Virus Nonstructural Protein 1
Yin P. Cheung, Valeria Mastrullo, Davide Maselli, Teemapron Butsabong, Paolo Madeddu, Kevin Maringer, Paola Campagnolo. mSphere Aug 2020, 5 (4) e00258-20; DOI: 10.1128/mSphere.00258-20
Candidates are expected to hold a BSc in biology, biochemistry, biomedical sciences or related subjects (2:1 minimum). An MSci/MSc or previous laboratory experience would represent an advantage.
Funding for this project is available to EU/UK nationals.
IELTS requirements: IELTS Academic 6.5 overall with 6.0 in Writing, or equivalent.