Divya Choudhary
Tell us a bit about the topic of your DPhil and why you chose it?
I am a trained engineer, having studied chemical engineering during my undergraduate degree. I was introduced to microbiology through research internships and, in particular, I explored how bacteria interact with each other and respond to their environment. For my DPhil, I was passionate to take an interdisciplinary approach combining mathematics and biology to look at why individual bacterial cells behave differently from each other when subjected to a stressful environment. Specifically, I studied bacterial response to oxidative stress by reactive oxygen species, which bacteria often experience during immune attack against infections and under antibiotics. I used advanced single-cell microscopy with microfluidics to investigate the heterogeneity in bacterial responses and applied machine learning to interpret the data. My first paper revealed that the seemingly random behaviour of individual bacterial cells is in fact governed by ‘hidden variables’, which were predicted by the machine-learning model and validated in experiments. In my second paper, combining theory and experiments based on the underlying factors predicted by machine learning, I found that chaotic dynamics, rather than randomness, drive fluctuations in bacterial oxidative stress responses. In the next paper, we demonstrated how these fluctuations are orchestrated by the master regulator of stress response within individual cells, resulting in a population-level protection against oxidative stress.
Would you encourage others to study for a DPhil in Biochemistry at Oxford?
Absolutely, and there are many different reasons why. The department is highly collaborative, both internally and with other departments such as Biology, Mathematics and Engineering. I had the opportunity to work with molecular biologists, biophysicists, and engineers, which was crucial because it helped me to solve complex problems. One of the papers I published was on chaos theory in bacterial responses. Each of my supervisors brought different approaches and ideas to this study, and together it was exciting to show how very small differences in individual cells’ states can lead to dramatic differences in their response to oxidative stress. I was also able to interact with the bacteriology community in departmental and interdisciplinary seminars. Another strength of the department was the feedback from my supervisors, and discussing my training needs and progress with them, which led to lots of insights on how my DPhil was progressing and helped me to maintain my excitement about my project.
Do you feel the process has opened up doors to the next stage of your life? If so, how?
Definitely. Even though I was from an engineering background, with little hands-on biology experience, with an interdisciplinary approach, the skills I developed during my time at Oxford can be applied to lots of different biology questions. My supervisors encouraged me to think independently, which has helped me as I move forward in my career, in particular with writing grant applications, and has encouraged me to continue in academia and to establish my own research group in a couple of years. Even though a DPhil is quite niche, it can have applications across other disciplines, and I was able to collaborate so successfully that I am still in touch with some of those who I worked with during my time at Oxford.
What do you feel has been the most important takeaway from your DPhil for you?
Understanding that some scientific questions and progress require an interdisciplinary approach to get the best results. By combining different techniques and methodologies you can not only get a better answer to a scientific question, but you can also challenge more complex questions. This takeaway was key because it helped me reach the findings of my DPhil. I also learned to try experiments that potentially have a higher chance of failure, as they might give you unexpected insights that open the door to various scientific nuances.
What have you gone on to do next?
I am currently a postdoctoral fellow at Harvard University. I have continued to take an interdisciplinary approach, and am based in both the Harvard Medical School and the Molecular and Cellular Biology department, with dual supervisors – one in each department. My research focuses on understanding antimicrobial resistance to guide novel ways of targeting infectious bacteria. When an antibiotic attacks bacteria, we know what it’s targeting. However, how the antibiotic actually brings about cell death once it has hit that target is not well known, and this is what I am currently investigating. Many studies have shown that not all bacteria respond in the same manner, and this variability can allow some cells to escape the antibiotic attack leading to reinfections. Hence, bacterial response to antibiotics poses two-fold complexity: cell-cell variability and a complex response involving multiple cellular mechanisms. I will acquire skills in genetics and microscopy techniques to build assays for identifying individual cells’ fingerprints, to learn more about which bacterial responses are critical for individual cells’ survival under antibiotics. Further, I will advance the interdisciplinary techniques I developed at Oxford to assess whether bacterial responses can predict whether an individual cell dies or survives under the antibiotic attack.
I always felt very supported during my time in the Biochemistry department. Just like bacteria, as researchers we also get stressed during our DPhil, so support is really important.