CPS Grad Spotlight - Euan Joly-Smith
Name:Euan Joly-Smith
MSc or PhD Candidate: PhD Candidate
Location of Undergraduate Education:
HBSc. in Physics and Mathematics at
McGill University
Name of the Lab at CPS: Hilfinger Lab
Selected Research Contributions:
Inferring gene regulation dynamics from static snapshots of gene expression variability [Link PDF] Joly-Smith E, Wang ZJ, Hilfinger A, Phys. Rev. E; 104:044406 (2021)
(Summarized in blog post https://uoftbiophysics.github.io/blog/2021/maturation-time/)
Euan, please tell us about yourself and your journey as a PhD Candidate!
How did you come to UTM? What interested you to join a lab here?
I first came to UTM during the summer before I started grad school, via a pre-doctoral summer research fellowship. I had always expected to go to grad school to research in a field of physics called ‘High Energy Theory.’ However, during my undergrad, a curiosity about biological systems began to reshape my interests. Questions of 'why are living systems the way they are? Are there any unifying rules that govern these systems? And can we make quantitative predictions for these systems as we do in other areas of physics?’ captivated my mind. I became drawn to such questions, but my chief attraction to the mathematics and methods used in High Energy Theory seemed to remain separate. Finding myself in a dilemma, I viewed this summer fellowship as a wonderful opportunity to explore a different field before I had to decide on a supervisor for grad school, and so I joined a theoretical biophysics group at UTM for the summer. I was pleasantly surprised to learn that the kinds of theories and quantitative analyses that I loved from my undergraduate studies could be used to study biological systems. Once I stepped into the captivating world of biological physics, there was no turning back.
When did you realize that you wanted to pursue a graduate study?
Going to graduate school became an immediate goal of mine once I began learning about areas of physics beyond classical Newtonian Mechanics in my first year of undergraduate studies. Courses that touched on things like the theory of relativity or quantum mechanics showed me how the world around us followed principles that I could not have imagined, which led to a deeper admiration for the laws of nature and an appreciation for their mysteriousness. As my interest to explore these topics increased, I knew I would want to take graduate courses on the subject. It was around this time that I learned how the history of physics often progressed as a series of reformulations; existing theories are experimentally shown to be wrong by probing unexplored phenomena and new theories — governed by new principles — are found to replace them. The realization that current theories are merely our current best approximations, and have the possibility to be ‘wrong’, excited me. There are amazing discoveries to be made! It became clear to me that I wanted to pursue research and graduate school was a natural next step.
What are your research interests? Tell us few exciting things about your research.
If you take any group of cells, with the exact same genome and grown in the same conditions, they will never be exactly the same. This is because molecular abundances in cells exist in relatively small numbers, such that the random nature of the chemical reactions underlying biochemical processes becomes significant. This cell-to-cell variability governs many biological processes, but in the Hilfinger Group we are interested in exploiting this variability as a source of information for the underlying biochemical networks that govern cellular behaviours. Crucially, state-of-the-art experimental methods in molecular biology now permit us to make quantitative measurements from this naturally occurring variability, providing a means to probe cells without having to perturb them.
However, this brings up two problems. First, these biochemical networks are complex and sparsely characterized. This makes it difficult to use mathematical modelling to translate data into an underlying process because there are so many possible models that can fit the same data. Second, many high throughput methods in molecular biology generate static population snapshots of cell-to-cell variability, making it difficult to probe cellular dynamics with such methods. In order to tackle these problems, I used a novel approach: by deriving mathematical bounds on whole classes of sparsely characterized systems, we can make rigorous predictions with only a handful of testable assumptions. Applying this approach on classes of systems modelling a commonly used gene expression reporter assay, I derived mathematical constraints that promise to translate static population snapshots of gene expression reporters into causal and dynamic properties of gene regulatory networks without using perturbations.
Naturally, these are theoretical results, so the question is: do they work in practice? synthetic genetic circuits provide exciting opportunities to verify our theoretical results with well-characterized engineered systems. Through the CPS Graduate Research Visit Program, I joined a synthetic biology lab in Montreal and was introduced to the daunting world of experimental biology. I was able to build a number of synthetic circuits in E. coli with different topologies, feedback mechanisms, and dynamics. These cells were placed in microfluidic chambers that allowed me to follow them over Ime for many days, using time-lapse fluorescence microscopy. By pooling the data into a static distribution, I aimed to demonstrate that my theory predicts the observed dynamics and the known topologies. The data is currently being analyzed, so the jury is still out. I hope to share the final results with you soon!
What is your goal when you finish your degree?
After finishing my degree, I plan on continuing in research, either at an academic institution as a postdoctoral researcher or somewhere in the industry.
What are some of your achievements you'd like to share?
During my time in grad school, I have had the privilege to travel to many scientific conferences around the world to give talks about my research. These conferences were excellent opportunities to learn about the latest research in our field, and also a very good place to meet fellow scientists that can help further our research and even lay the foundations for future collaborations. By travelling and giving these talks, I was not only able to promote our work to a larger audience, but I was fortunate enough to receive lots of valuable feedback, much of which I am still using today to guide my research.
Do you have any advice for students considering to pursue graduate studies in research?
Above all, to follow your curiosity. Graduate school should be a fun and fulfilling experience. I suggest all prospective grad students take the time to find a project that they find fascinating and that they can see themselves spending lots of time thinking about. When it’s the right match, I can say from experience that every day of research can be as exciting as the first.
Additionally, do not be scared to cross research boundaries or start collaborations. I’ve met many experimentalists that say they could never do theory and vice versa. I think graduate students should be open to the possibility of learning new skills through collaborations and/or visiting other labs. It takes time and work, but it is entirely possible, and ultimately is an incredibly rewarding experience. Do not let yourself be constrained by the seemingly fixed barriers between disciplines– follow your curiosity.