Breaking down Tuberculosis’ Defences at the Molecular Level
By Will Conrad
Tuberculosis (TB) remains a major global health problem worldwide. According to the WHO, it’s one of the top 10 killers globally of all diseases. In the developing world it’s estimated that people have a 50% chance of getting exposed to mycobacterium tuberculosis (Mtb), the cause of TB, over their lifetime.
My research seeks new strategies to identify anti-TB therapies. Specifically, I am looking at how mycobacteria defend themselves against host immune systems. When Mtb gets into the lung, a patrolling immune cell called the macrophage engulfs it and carries it deeper into the lung tissue. The macrophage attempts to wrap Mtb with membranes and digest it in specialized organelles. Unfortunately, Mtb has devised a way to escape these membranes to survive and thrive.
My research asks the simple question, how do mycobacteria destroy host membranes to live within macropahges? Genetic, functional, and biochemical research by myself and others has identified the genes involved in this process. However, we still don’t know how these genes function to destroy membranes. My work seeks to understand the function of the specific genes involved in order to target them for therapy.
It has been an honour and a great benefit to do this work whilst affiliated with Clare Hall. The truly interdisciplinary nature of Clare Hall has meant interacting with students and Fellows from incredibly diverse backgrounds. Chance conversations over formal hall dinner or at the endowed lectures have led me to think differently about my own work and also given me a refreshing perspective on all of the exciting research happening at Cambridge that’s outside my own discipline.
I especially have benefitted from the Clare Hall postdoc association’s “Three slide talks”. It was an incredible challenge to distil my research project into three slides meant for a general academic audience. It was a truly rewarding experience as the attendees were generally enthusiastic, optimistic and engaging. My research was questioned in ways that differed greatly from a more specialized audience, and led to an incredibly engaging discussion. Ultimately, I used that practice to help develop my “job talk” for a more diverse audience. This practice certainly helped me to successfully land a faculty position in the US.
Will Conrad was an affiliated Postdoc at Clare Hall (2017-18) and is now starting an Assistant Professorship position at Lake Forest College, Chicago.