(4c) Decoding and Expanding Cellular Functions for Living Technologies

Engineered cells can address unmet needs for human and planetary health, including the controlled production of valuable compounds or degradation of hazards in situ. To understand and engineer cellular functions, we need experimental and computational tools that 1) predict and design phenotypes and 2) control proliferation.

During my graduate studies, I worked on targeting malaria parasites through the computational understanding of cellular metabolism. I developed mathematical formulations that identify cellular processes underlying phenotypes, nutritional requirements, and high-order synthetic lethal interactions. I constructed the most comprehensive genome-scale metabolic models of highly uncharacterized malaria parasites and achieved 80% accuracy in essentiality predictions, as proven by experimental data. In this collaborative project with experts in malaria, I co-discovered seven metabolic pathways essential for survival in liver-stage malaria parasites. This knowledge is guiding the design of metabolically attenuated parasites for a malaria vaccine.

During my postgraduate studies, I engineered strains of Escherichia coli for controlled proliferation, function, and use of new biochemistries. Currently, bacteria used as platform technologies rely on a wild-type genetic code, which can result in horizontal gene transfer, escape, and loss of control of the designed programs. Genetic code engineering emerges as a promising alternative since it removes a set of codons and tRNAs from the genome. Without the possibility to read all wild-type codons, bacteria with an engineered genetic code should not translate incoming DNA. Surprisingly, I discovered a new mechanism of escape in bacteria with an engineered genetic code and characterized it with multi-omics data and protein language models. This finding allowed me to develop a biocontainment mechanism that also prevents malfunction of recoded cells. My engineered cell is the first organism that enables the production of proteins containing up to three non-standard amino acids while remaining tightly biocontained and bioisolated.

I would like to continue developing my cellular engineering toolbox involving computational and experimental analysis of genomes, proteins, and metabolism to decode and expand cellular functions. This work will result in living technologies with controlled programs involving new biochemistries. I will apply these tools to prevent and target antimicrobial resistance.

Teaching Interests:

Beside my research, I also have a passion for mentoring and teaching. Throughout my PhD and Postdoc, I have supervised 32 student projects including 19 semester, 7 master, and 6 sections of PhD projects. All of these students have been excellent in their own way and have taught me to be a better scientist and mentor. It is until today that I remain in contact with them for career advice and support, and it makes me very happy and proud to see them grow and succeed. For outstanding mentorship service to women in the field of Chemical Engineering, I received the 2023 Mentorship Excellence Award from WIC AIChE.

During my undergraduate years, I organized study sessions with my classmates to help them with advanced calculus. Later during my Ph.D., I fostered my passion for teaching. I taught more than 1,000 hours in 5 years. This involved three undergraduate courses in which I was a project mentor or teaching assistant, three workshop courses in which I participated as a service teacher, and a graduate course at which I taught. The main course I taught for four year was “Introduction to Chemical Engineering” involving mass and energy balances. I introduced active learning techniques in my classes, for which I won the Excellence Teaching Award by the Chemistry and Chemical Engineering section at EPFL in 2016 and the appreciation of many students with whom I remain in contact. At Harvard and MIT, I have had the chance to teach two courses in the spring of 2022 involving more than 250 students. As a faculty, I would like to teach foundational courses of chemical engineering and I would also enthusiastically introduce courses on computational biology, systems biology, or synthetic biology, among other options that could match the offered study programs.