Project-I: Understanding virus-host interactions and transport mechanisms across intact nuclear pores and inside the nucleus of mammalian cells
In the lab we study the capsid dependent HIV-1 biology, namely disassembly (uncoating) and nuclear transport steps using live-cell imaging techniques. Current projects in the lab focuses on delineating the molecular mechanisms of HIV-1 transport inside the nucleus. This project build on the discovery of the existence of a default nuclear transport pathway across multiple cell-types that results in the accumulation of HIV-1 VRCs inside membrane less nuclear speckle compartments (Francis et al, Nature Comms 2020). This project will also explore new strategies to fluorescently label the capsids and replication complexes of other viruses that transit through the nucleus, including Retroviruses (MLV), Lentiviruses (SIV, EIAV) and Hepadena virus (HBV) to illustrate their life cycle.
Project-II: Ultra-structural characterization of virus disassembly and transport by 3D correlative Light and cryo-Electron Tomography (cryo-CLEM).
Whereas fluorescence live-cell imaging provides spatial-temporal information of virus/host interactions, we are also interested in understanding the structural basis for this process. Current projects focus on establishing the baseline morphological features of HIV-1 uncaring intermediates bound to EM-grids, during its interaction with host factors in vitro. The in vitro hi-res structures will serve as templates for identifying HIV-1 interactions inside living cells at the nuclear pore, and at sites of integration. This research will lead to the development of additional tools that improve throughput of single virus detection in 3D for correlation driven focused ion beam (FIB)-milling at thick regions of cells and Cryo-ET data acquisition.