Exploiting viral regulators for synthetic biology toolbox development for Sulfolobales

Bacteriophages have been indispensable for the development of
synthetic biology toolboxes for bacteria. In contrast, despite the
natural abundance of archaea-specific viruses, similar efforts have
not yet been undertaken for archaea, which have a great
biotechnological potential. In this project, I will focus on the family of
Sulfolobus spindle-shaped viruses (SSVs) infecting thermoacidophilic
archaea belonging to the order of the Sulfolobales. The multi-stage
infection process requires a tightly orchestrated gene expression
program, which is coordinated through interaction with the host’s
transcription machinery. While several transcription regulators are
encoded in the SSV genomes, little is known about their function and
mechanism of action. With the aim of identifying and characterizing
SSV-encoded transcription regulators that mediate a switch-like gene
expression response that can be harnessed for synthetic biology
engineering, I will employ genetic, genomic and biochemical
methodologies to elucidate their role in the virus-host relationship.
Building on this knowledge, orthogonal synthetic genetic circuits will
be constructed in S. acidocaldarius, a biotechnological platform
species that is not susceptible to viral infection. By bridging critical
knowledge and application gaps, this project will take the first steps
in developing efficient synthetic biology tools for the engineering of
Sulfolobales.