Dr Niluka Goonawardane

Introduction

We use a range of multidisciplinary approaches to investigate why neurotropic viruses with close homology cause drastically diverse disease outcomes in humans. We employ the latest physiologically relevant models of infection, including 3D human cerebral brain organoids and Blood-brain barrier (BBB)-organ chips to study these viruses.

A key aim of the lab is to understand how viruses manipulate signaling in neuronal and non-neuronal cells and how this contributes to disease severity, virus persistence and pathogenesis.

Current major projects

• Why do closely related virus strains cause drastically different clinical outcomes in humans?
• Which viral- and -host factors dictate this differential pathogenicity?
• Development of new imaging-, omics- and ex vivo approaches to study virus infection at the nanoscale.
• Identifying new angles for antiviral drug development based on this knowledge.

Detailed research programme

We focus on tick-borne encephalitis virus (TBEV), a virus that is emerging across Europe with sometimes fatal outcomes. TBEV circulates as five closely related subtypes that lead to drastically variable disease profiles. We recently discovered a number of cellular- (IRF-3, BCL2, G3BPI) and viral factors [NS1, NS3 and NS5]) that dictate this variable pathogenicity. Building on this knowledge, we use nano-resolution imaging and multi-omics approaches in the latest 3D tissue models to understand this relationship at the molecular level. We are pursuing the translational significance of our discoveries for antiviral drug development.