A new 3D system that can be used to study human infection in the lab has been developed by researchers at the University of Southampton. The team includes engineers, infection researchers and bioinformaticians at the University of Southampton and at University College in London.
Using an electrostatic encapsulation technique, the team makes tiny 3D spheres within which tuberculosis (TB) bacteria are used to infect human cells. This generates conditions that reflect events in patients closely.
The research was funded by the Medical Research Council and published in mBio. A similar study was also published in eLife. The model allows the researchers to investigate what transpires in a human body when TB develops. The long-term aim of the research is to identify new antibiotic vaccines and treatments.
Professor Paul Elkington leads the Southampton TB research group. He believes that this is an exciting development in the field of tuberculosis research. To make the 3D sphere more like a human lung, it is created with a collagen matrix. This creates an environment that allows specific antibiotics that are important in treating patients, to kill the infection, something that can’t be done in other 2D model systems. Elkington notes that this system will help speed up the process of finding vaccines and treatments for human tuberculosis. TB kills an estimated 1.8 million people per year worldwide.
The 3D spheres are also able to prolong experiments for up to three weeks. This is more than four times longer than what standard 2D model systems can achieve. This allows researchers to gather more information on how the infection develops, and the effects of various interventions over time.
In a project being funded by an MRC Global Challenges Research Fund Foundation Award worth £350,000, the next phase of the research will be in partnership with the African Health Research Institute in Durban, South Africa. There is a very high incidence of TB in Durban and the ideal laboratory infrastructure does exist to introduce the 3D model to study cells from patients at high risk of TB.
Professor Elkington is delighted to have the opportunity to combine diverse expertise to develop an advanced laboratory system and to extend the research. The aim is to apply the system to a wide range of infections, especially those that are prevalent in countries that don’t have many resources. The 3D model will be used to integrate biological and engineering approaches with clinical specimens. This combination will create an entirely new system of studying infection.
Dr Al Leslie of the Africa Health Research Institute noted that there is a huge amount to be gained from engineers and infectious disease biologists working together, as the different disciplines tend to push each other out of their comfort zones. This fosters a new perspective on the problem being tackled.
Leslie added that the grant is the beginning of what could possibly become a long-term collaboration that will bring real innovation to Africa’s TB research programs. This should speed up the pace of discovery to fight this deadly epidemic dramatically.