Research Themes: Biocatalysis, Protein & Metabolic Engineering, Synthetic Biology, Directed Evolution
Research in the Cirino lab generally aims to improve “biocatalysis” (broadly, enzyme- and/or microbial-based conversion of chemical feedstocks into higher value chemical products). This includes advancing production of renewable fuels and chemicals, and repurposing or otherwise harnessing often complex natural chemical transformations orchestrated by one or more enzymes. This is accomplished through protein and metabolic engineering, and synthetic biology applications. Most notably, we have pioneered the customization and use of bacterial transcription factors as genetically-encoded biosensors/molecular reporters for high-throughput biocatalyst screening.
Example of what we do (image below): Link to publication.
Current projects include:
- design of biosensors for minimal polyketides / engineering type-III polyketide product specificity
- engineering coli for anaerobic biological activation of short-chain alkanes via fumarate addition
- engineering / directed evolution of alkylsuccinate synthase substrate specificity
- engineering ligand specificity of the ItcR repressor for biosensor applications
Further details on these projects can be found here (graduate student projects).
In collaboration with other labs, we more broadly develop and apply molecular and synthetic biology tools. For example, we are developing controllable / inducible gene expression systems in human T-cells using an engineered bacterial repressor protein (MarR) (collaboration with Navin Varadarajan (UH) and Dmitry Nevozhay (MD Anderson Cancer Center). Working with Jacinta Conrad (UH), we are designing novel, tunable “appendage” mutants of E. coli and M. hydrocarbonoclasticus; these are useful for studying/engineering bacterial adhesion in bioremediation applications, and bacteria-driven emulsions.
Ramon Gonzalez (USF)
Costas Maranas (PSU)
Navin Varadarajan (UH)
Dmitry Nevozhay (MDACC)
Jacinta Conrad (UH)
Jeremy May (UH)
Recent News and Highlights:
Link to some Cirino lab news items: https://www.egr.uh.edu/faculty-news/dr-cirino-patrick-c
- Congratulations to undergraduate student Carson Bush for being awarded a 2021 Summer Undergraduate Research Fellowship (SURF), to work in the Cirino lab.
- Aarti Doshi (linkedin) defended her Ph.D. thesis and started a new job at Tessera Therapeutics! Congrats Aarti!
- Aarti Doshi published a detailed review on “Small-molecule inducible transcriptional control in mammalian cells”
- Cirino presented new research on producing alkylsuccinates (invited talk at AIChE annual meeting)
- Congrats to Zhiqing Wang, Aarti Doshi, and others, for publishing manuscript describing “highly evolved” AraC variants! Wang et al., Protein Engineering, Design and Selection, Vol 33, 2020, gzaa027, https://doi.org/10.1093/protein/gzaa027
- AIChE Journal special issue (co-edited by Cirino) commemorates Frances Arnold
We gratefully acknowledge the National Science Foundation for numerous grants to support these research projects.
Key words/terms: Biotechnology, Biocatalysis, Protein Engineering, Metabolic Engineering, Synthetic Biology, Directed Evolution, High-Throughput Screening, Alkane Activation, Alkylsuccinate, Transcription Factor, Gene Expression, Molecular Reporter, Biosensor