My lab focuses on harnessing biology via the discovery of new chemical transformations from nature and the manipulation of biosynthetic pathways to create new complex molecules via heterologous expression. We essentially do our chemistry within microorganisms. We focus on complex biosynthetic enzymes such as polyketide synthases and non-ribosomal peptide synthetases which biosynthesize therapeutic molecules, many of which are used in the clinic. This research has applications in medicine, sustainability, and expanded biomanufacturing.
Tell us about your background and how you came to join the School of Chemistry.
I started my academic career by receiving my bachelors degree at a small institution in Portland, Oregon called Reed College where I fell in love with organic chemistry, but I was always intrigued by the idea that so much effort was spent on trying to synthesize natural products which microorganisms make with simple building blocks. After doing a stint in an organic synthesis lab, I spent a summer doing a research internship in a lab at the Hans Knoell Institute/Leibniz Institute for Natural Products and Infections Biology in Jena Germany working on an engineered natural product. I fell in love with this field and spent my undergraduate thesis characterizing biosynthetic enzymes. After this, I pursued PhD studies with a new professor at the University of Texas-Austin who was studying polyketide synthases which are the enzymes responsible for making complex natural products like the antibiotic erythromycin. This led into trying to understand how to make molecules through bioengineering in the lab of Jay Keasling at UC Berkeley/Lawrence Berkeley National lab. I started my career in the US at the University of Tennesee-Knoxville and moved here because I felt like it was an incredible environment to do chemical biology, especially in the peptide natural products area!
What have you liked most about working in the School so far?
My favorite part about working in the School are the people. In terms of my colleagues, from Peter Ruledge’s leadership to the incredible discussions of science and pedagogy to the personal connections I have made, I feel like we have a very special energy in the school right now that I love being part of! The students have also been incredible—I have a really great team in my lab. I have also been able to teach and mentor some very talented undergrads.
At the moment, I am working on…
I am working on a few different projects. One project is using heterologous expression to make a peptide natural product that is an important antibiotic lead. Another is to use heterologous expression and cell free expression to characterize peptide natural products isolated from the environment in Australia. Finally, I have some projects on better adapting expression systems outside of the cell to make complex but biocatalytically interesting enzymes from biosynthetic pathways.
What are the big ideas in this field? Where do you think it’s heading in 10 years? What will your field deliver for society?
My research is in the field of synthetic biology, specifically as it applies to using enzymes from bacterial natural product biosynthesis to make new molecules including therapeutics and other specialty chemicals. I believe this is a really important area because many of these molecules are challenging to make and create derivatives of synthetically, and at the end of the day generating them through fermentation is likely the most scalable. In addition, nature does so much fascinating chemistry that can be difficult to recapitulate in a flask. As biotechnology becomes more and more advanced, we have more and more opportunities to reliably use biology to do our chemistry. I think this is incredibly exciting, and just getting more powerful. I also believe it is the future of biomanufacturing.
What’s your favourite part of Chemistry? Of being an academic at a university?
My favorite part of chemistry is learning chemical intuition and having a good feel for chemical reactivity. I think many people see biology and chemistry as separate entities, but to me it really all comes down to how electrons move and kinetics and thermodynamics—it just gets messier as the systems get more complex! I like being able to draw the connections between simple concepts I teach in first year and how biology works—like showing the resonance structure of an amide and linking it to how we can understand protein folding. Or teaching kinetics and linking it to enzyme function. My favorite part of being an academic is that I learn so much and what I’m learning is always changing. My group makes new discoveries, and to work in such an interdisciplinary space I am constantly learning new techniques or new subfields. But as an academic I learn other things too. I learn how to teach, how to mentor, how to navigate bureaucracy, how to organize scientific communities, and experience different cultures. It’s a pretty cool job because you never get stuck doing one thing.
What is the coolest thing you’ve seen/done in the lab?
The coolest thing I have done in the lab is do a 20L fermentation of a bacteria with an engineered pathway, fed it a precursor I synthesized at the fume hood, and then put it on an industrial scale rotovap and run several columns to purify a compound out of it. I just felt like it was so cool to do a transformation inside a cell!
And what about outside the lab?
Outside the lab one of my hobbies is running. I ran the Boston marathon a couple times, and that was which was a dream I had since it was the world’s oldest marathon and has been run since 1897 so you can really feel the history. I got to meet a few Olympians just walking around Boston before the race as well, which was neat.
My favourite place on campus is…
I like walking towards the Quadrangle coming up the stairs from the entrance near Victoria Park. It just reminds me of how beautiful the campus is.
Something that might surprise people about me is…
I was absolutely horrible at chemistry in secondary school, and no one would have ever thought I would be a chemistry professor.
Do you have a message for our Alumni and friends of the School?
I have worked in several chemistry departments, and Sydney has an exceptional level of collegiality and supportiveness. I feel really grateful for all my colleagues and mentors here, and for all the wonderful students.