Motivation
We apply ourselves to understand how some Flavivirus are able to bypass some of the strongest physical barriers in our body to cause severe health outcomes. We aim to apply our skills to improve health outcomes for everyone.
Viral budding and Zika virus protein-protein interactions
Zika virus (ZIKV) belongs to the Flaviviridae family, which also includes Dengue and Yellow fever. These are very small enveloped viruses (~50 nm diameter) with a single-stranded RNA genome of ~11 kilobases in length. The genome encodes for 11 proteins. These proteins bear great sequence and structural similarities across the different Flaviviridae.
In Flaviviruses, the prM prevents the E protein from undergoing early conformational changes responsible for virus-endosome membrane fusion. The TMs of E and prM do not interact in the mature or immature virion. However, there is evidence that mutation of the prM protein of DENV has a negative effect on viral entry. We are particularly interested in the ZIKV structural membrane proteins M and E and their interaction with the Capsid domain to promote viral budding. We aim to understand how these protein initiate the process of membrane bending utilizing nuclear magnetic resonance.
Virus-Host Protein Interactions and the Placenta
Viral infections can have devastating consequences during pregnancy, ranging from miscarriage, and fetal malformation to preterm and stillbirth. Some of these negative outcomes are caused by vertical transmission (parent-progeny) to the fetus. One of the main roles of the placenta is to protect the developing fetus from pathogens, yet some viruses are able to bypass this strong barrier and directly infect the fetus. Zika virus (ZIKV) is one of these viruses.
The molecular mechanism by which ZIKV bypass the barrier of the placenta is not completely understood. Many mechanism have been proposed and probably more than one pathways exists. A mechanism of particular interest is the viral hijack of extracellular vesicle (EV) pathways to deliver viral proteins and RNA. EVs are essential communication tools between mother and fetus and have no obstacles crossing the placental barrier. In our laboratory, we aim to understand the protein-protein interactions between ZIKV and the hosts’ proteins that enable ZIKV to hijack the EV pathway in the placenta. For this purpose, we utilize cell biology, biochemistry, cryo-electron microscopy, and nuclear magnetic resonance.
Methods
Some awesome graphics coming soon!