Successful ARC Discovery Project 2024
Published by NDF staff, 1st November, 2023
NDF researcher Dr Anthony Duff is a partner investigator on a recently awarded 2024 ARC Discovery Project grant valued at $624,710 entitled "The geometry of genome access: lessons from HIV".
Access to the cell’s nucleus, and hence its genome, is of deep scientific and commercial significance. It is controlled by a phase-separated diffusion barrier within the nuclear pore complex. Recent evidence, however, has shown that HIV can cross this barrier with its protective capsid intact, despite it being over one thousand times larger than the limit for passive transport. Combining concepts from soft-matter physics with recombinant assays, this project aims to uncover the link between the unique geometry of HIV capsids and their ability to subvert the nucleus’ defenses. The expected outcome is a step-change in the understanding of nuclear access control, with downstream benefits to virology, bio-engineering and bio-technology.
To study the penetration of the HIV capsid into the nuclear pore complex, a series of neutron reflectometry experiments are planned. In the first, scheduled for early 2024, deuterated HIV capsids will be added to a floating monolayer of the polypeptides that fill the nuclear pore channel, to reveal the depth to which the capsid initially sinks.