Engineering Improved TB Therapies
The highly anticipated bimonthly seminar and mixer event on April 7th featured a presentation titled Engineering Improved TB Therapies, by our guest speaker, Dr. Bree Aldridge. Dr. Aldridge is an Assistant Professor from Department of Molecular Biology and Department of Biomedical Engineering, Tufts University. The event was moderated by Boston QSP advisor Dr. Frank Gibbons, Principal Scientist, Modeling & Simulation, AstraZeneca.
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. “A third of the world population is infected with TB,” Dr. Aldridge explains, “It is a leading cause of death in the world due to a single infectious agent. It kills more people than HIV-AIDS and malaria.” One of the major challenges in anti-TB treatment development lies in the heterogeneity of the mycobacterial population, resulting in differential susceptibility towards antibiotics. TB patients typically take four drugs for the first 2 months. They need to continue taking two drugs for an extended period of four months. Understanding the underlying cause of differential susceptibility and efficiently measuring the effects of drug combinations are important steps toward engineering improved TB therapies.
Through live-cell imaging at a single-cell level, the Aldridge group showed that Mycobacteria grow asymmetrically in a deterministic way. The rod-shaped cell grows faster on the old pole called “growth pole” and then divides. A cell resulting from a growth pole is called an accelerator cell. A cell resulting from the opposite non-growth poles, then, is called an alternator cell. Alternator cells grow slowly and are smaller. Depending on the age of the growth pole, where a cell is in the cell cycle, and the size of the cell at birth, cells have differential antibiotic susceptibilities. Dr. Aldridge and her lab revealed that a new model of regulating cell size control called the “parallel adder model” explains the “quirky” growth behavior in Mycobacteria.
Owing to the differential susceptibility of the Mycobacteria to antibiotics, a typical treatment of TB takes months of multiple drugs. In this context, Dr. Aldridge and her collaborators developed a new method called DiaMOND (diagonal measurement of n-way drug interactions) to efficiently measure the drug interactions that works for both lower order and higher order drug combinations. To learn more about DiaMOND and research from the Aldridge Group, click here.
The talk was followed by a mixer event where community members discussed and socialized over food and drinks.
We got a chance to ask a few questions to Dr. Aldridge after the event. When asked about how she got interested in studying TB, she said, “I started my research career in systems biology and cancer biology, but traveling made me wonder if we couldn't bring over quantitative approaches from the cancer research field to infectious diseases. When I started to learn more about infectious diseases, I developed a special interest in TB because there was still so much to be learned about the cell biology of the pathogen.”
To the students and postdocs who are trying to find their research directions, she advises, “Talk as much as you can about your ideas with others, especially those who use different tools.”
Please note that the event was re-scheduled from its original date in March due to a rough weather forecast.
We would like to thank all our guests for their understanding and enthusiastic participation despite of the re-schedule and a not-so-pleasant weather even on the event day of 7th April. We would also like to thank AstraZeneca for sponsoring the event and CIC for sponsoring the venue.
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About Boston QSP
Boston QSP is a 501(c)(3) non-profit organization whose mission is to foster the sharing of QSP knowledge, challenges, solutions, and opportunities to advance the field as an interdisciplinary community in Boston.