Thursday, February 8, 2024 | 4:15pm to 5:15pm
About this Event
Engineered cells can address unmet needs for human and planetary health, including the controlled production of drugs or degradation of hazards in situ. To develop safe cell-based technologies, we need cellular engineering tools that 1) predict and design phenotypes and 2) control proliferation.
In the first part of my talk, I will discuss my work targeting malaria parasites through the 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.
In the second part of my talk, I will present my project on engineering an ultra-safe strain of Escherichia coli. 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. Fascinatingly, I discovered a new mechanism of escape in bacteria with an engineered genetic code and characterized it with multi-omics and protein language models. This finding allowed me to develop an ultra-safe 61-codon E. coli strain. In this strain, I engineered a tRNA/aminoacyl-tRNA synthetase pair for the incorporation of a non-standard amino acid and implemented kill switches. This is the first organism that enables the production of proteins containing user-defined non-standard amino acids while remaining tightly biocontained and bioisolated.
My work is a head-start to develop ultra-safe living technologies and will allow us to decode and expand genome and protein designs.
0 people are interested in this event