The Bill & Melinda Gates Foundation has awarded a three-year $1.1-million grant to K-RITH Investigator Dr Al Leslie to fund an exciting project in human granuloma sequencing analysis.

Working with collaborators Dr Samuel Behar from the University of Massachusetts, Dr Evan Newell from the Singapore Immunology Network and K-RITH’s Dr Alex Pym, the project will see them applying cutting edge sequencing and phenotyping techniques torevolutionise our understanding of the TB immune response in human lung tissue.

While it’s common knowledge that the immune system is essential in controlling TB infection, most obviously because the large majority of people who are TB infected never get sick, we still don’t properly understand what the important protective immune responses are in humans. To date, most human TB immunology work has been done in the blood. However, we are yet to develop an effective TB vaccine, which has led researchers to hypothesise that the answers to TB immunity may lie elsewhere.

Leslie explains that the last major work done on fresh TB lung samples happened 50 to 60 years ago, which was well before modern immunology techniques were available. This grant will enable his team to apply advanced technology to a set of lung samples, gathered in collaboration with the University of KwaZulu-Natal’s Thoracic Surgery Unit at King Dinuzulu Hospital Complex and Inkosi Albert Luthuli Central Hospital. The unit undertakes among the highest number of lung resections for resistant TB in the world. Using next generation sequencing, cell sorting and mass cytometry Dr Leslie hopes to discover whether or not the specific immune responses seen for TB in the blood match the responses in the lung. Part of their work will also be updating our knowledge of what happens in a TB infected lung.

The K-RITH work is happening in parallel with another Gates Foundation-funded study in the United States, which is doing similar research in non-human primates. It’s hoped that when taken together the results will give scientists a better understanding of TB immunity and ultimately allow them to come to a sound vaccine design strategy. The research falls under the ambit of The Collaboration for TB Vaccine Discovery.

“To do this work, you need to have a cutting edge research institute like K-RITH, and you need to be close to a hospital where there are surgeons who are taking out TB infected lungs. We work with doctors who are passionate about research and the opportunities that science presents to improve the care they give their patients,” Dr Leslie sums up.

“This research represents, in a nutshell, the reason for K-RITH’s existence here in Durban.”

* Dr Leslie is looking for a candidate to join his K-RITH lab on a fully funded two-year postdoctoral fellowship to work on this project. More details here.