A student-designed DNA scaffold that helps provide new insights into self-assembling biological systems has taken out the Grand Prize at Harvard University’s annual BIOMOD challenge.
The international competition invites teams of undergraduate students from around the world to develop new nanotechnologies using DNA, RNA and proteins.
Past winners have developed prototypes for nanotherapeutics and molecular robots. However, 2017’s winners – UNSW’s Capsid Constructors – had other ambitions.
The eclectic team – from backgrounds in chemical and biomedical engineering, molecular and microbiology, physics, law, communications and even music – aimed to use their DNA platform to help characterise the spontaneous construction of the human immunodeficiency virus (HIV) in living systems.
In particular, the team’s focus was on the protein capsule containing the virus’ genetic material, called the capsid.
The team hoped that by understanding the process behind self-assembly, they would be able to define a possible new target for anti-HIV therapies and create a robust method that could be used to define other self-assembly phenomena in nature.
To recreate the capsid’s formation under physiological conditions, the team engineered a platform from folded DNA to anchored the capsid proteins.
These captured proteins act as seeds, encouraging surrounding proteins to aggregate and form the larger subunits of the capsid – either groups of five or six proteins called pentamers or hexamers, respectively.
Using short sequences of modified DNA to tether the proteins to the platform, the team were able to conduct various experiments to control and observe the interactions between proteins.
The data from these experiments allowed them to develop a mathematical model that could explain and predict how these proteins come together, as well as other systems of self-assembly.
A new hope in the fight against HIV
With HIV rapidly developing resistance to antiviral therapies, biomedical researchers are having to get more creative in the ways they target the virus, and like in any battle, knowledge is power.
In recent years, researchers have homed in on the capsid as a potential mark. Already, the capsid plays a critical role in protecting the virus from environmental factors and detection by host cells. However, it is also thought to play a role in mediating the transfer of genetic material into the cell’s nucleus for replication.
By understanding how the capsid assembles itself in the body, researchers might be able to develop new therapies that can interfere with protein organisation and binding to prevent new viral particles from spreading.
The capsid is an even more attractive target because of its ‘genetic fragility’. There is immense pressure on the capsid proteins to form the intricate cone-shaped structure with optimal stability and the ability to interact with host cells without alerting them to the invasion.
This means they have very little room for mutation and will have a much more difficult time building resistance to new therapies.