Development of an engineered microbe for inflammation sensing in the intestinal environment

• Grant number: 19/00478-4
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: April 01, 2019
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Rafael Silva Rocha
• Grantee: Kauan Ribeiro de Sena Gomes
• Supervisor: David McMillen
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Toronto Mississauga (U of T Mississauga), Canada
• Associated to the scholarship: 18/03274-8 - Application of synthetic biology in the construction of genetic circuit to improve the antitumor effect of Salmonella spp., BP.MS

Abstract

Synthetic biology directed to biomedical applications aims to develop engineering-driven approaches to the programming of cellular functions that could yield transformative diagnostic tools, as well as unmatched therapeutic strategies for treating significant human pathologies. Our ability to generate bacterial strains with unique and increasingly complex functions has rapidly expanded in recent times. New tools are being developed for fast, large-scale genetic manipulation; and more tested genetic parts are available for use, as is the knowledge of how to use them effectively. These advances promise to unlock an exciting array of 'smart' cells for clinical use. Recent advances in the development and testing of engineered cellular systems highlight new technologies that will assist the development of more complex, robust and reliable treatments for future clinical applications, such as cancer and chronic inflammatory diseases. As cells interact intimately with their niche in the human body, they respond to a range of diseases and are well tuned by evolution towards detecting and producing physiological levels of biomolecules of interest. It is the combination of these features with the abilities of living systems, such as chemotaxis and biomolecule secretion, that could allow engineered biological systems to one day outperform traditional diagnostics and therapeutics in current use. Through this project, we propose to use the recent advances of synthetic biology to improve the natural ability of bacteria to act as an engineered therapeutic and target the pathological pathway involved in the development of inflammatory bowel disease (IBD). We intend to apply the knowledge gained in the design and construction of the genetic circuit directed towards IBD to leverage the engineering properties of our system fabricated to target cancer cells in the context of oncotherapy. (AU)