Synthorx, a Sanofi company, has developed a semi-synthetic organism. This organism was derived from E. coli and engineered to store an unnatural base pair in its DNA, which it transcribes into RNA and uses during translation to produce proteins with unnatural amino acids. Synthorx is currently using this bacterial semi-synthetic organism to develop next generation protein therapeutics. We are now seeking scientists to join the Synthorx Platform Innovation team to work towards the creation of eukaryotic-based semi-synthetic organisms. As efficient translation has already been demonstrated in CHO and HEK cells (A. X.-Z. Zhou, K. Sheng, A. W. Feldman, F. E. Romesberg. 2019 Progress toward Eukaryotic Semisynthetic Organisms: Translation of Unnatural Codons. J Am Chem Soc 141:20166–20170), the successful applicant will be part of a team that first focuses on optimizing the expression of a heterologous nucleotide transporter that imports the required unnatural triphosphates. With the triphosphates made available within the cell, the team will then focus on characterizing/optimizing replication and transcription. Finally, the semi-synthetic eukaryotic cell will be used to produce proteins containing non-canonical amino acids for development as next generation therapeutics. The successful candidate will also aid in the coordination, planning, and execution of existing and new collaborations with other groups within Sanofi to explore the development of novel therapeutics for different applications.
Explore and optimize the expression of different nucleotide transporters in eukaryotic cells (e.g. yeasts (S. cerevisiae, P. pastoris) or human cell lines (CHO, HEK).
Perform nucleotide-uptake assays.
Collaboratively design and implement experiments to characterize and/or optimize the retention of the unnatural base pair during DNA replication and transcription.
Characterize the fidelity with which non-canonical amino acids are incorporated in expressed proteins.
Support efforts to optimize the production of proteins with non-canonical amino acids, including one or multiple instances of the same or two different non-canonical amino acids.
PhD in appropriate field. No postdoctoral experience required.
Experience with eukaryotic genetics (e.g. yeasts (S. cerevisiae, P. pastoris) or human cell lines (CHO, HEK).
Experience with, and general understanding of, protein trafficking, DNA replication, and/or transcription in eukaryotic cells.
Experience with, and general understanding of, heterologous protein expression in eukaryotic cells.
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