Welcome to the Lee-Parsons Lab!

Overall vision of our research:  Plants produce a wide array of valuable, biologically active natural products that we use as medicines (i.e. anti-cancer, anti-viral, anti-infectives, anti-microbials).  While the plant is an amazing chemist, these compounds are produced in limited concentrations.  The overall vision of our research is to understand how the cells of the plant regulate production towards the goal of engineering their enhanced production and meeting the need for these critical plant-derived pharmaceuticals.

Approach:  Our model system of interest is the production of terpenoid indole alkaloids (TIAs) from cultures of the Catharanthus roseus plant.  The C. roseus plant produces several highly-valued TIAs, including the anti-cancer drugs vinblastine and vincristine.  The high cost ($4 – 60 million/kg) and need for these anti-cancer compounds motivate our research to better understand their biosynthesis and ultimately overproduce these valuable TIAs economically and reproducibly using engineered C. roseus plants or cultures as the production platform.

To realize that vision, our research seeks to elucidate the molecular mechanisms underlying the regulation of plant specialized metabolism and to apply bioengineering and bioprocess strategies in bringing these discoveries to reality. Specific examples of the molecular mechanisms studied include:  1) the intricate balance between primary and specialized metabolism (Oldham et al, 2010), 2) the coordination of growth versus defense processes in the plant by pivotal transcription factors at the interface, and 3) the network of transcription factors that interact to regulate plant specialized metabolism (Goklany et al, 2013; Rizvi et al, 2016).

Through these studies, we identify bioengineering targets (e.g. transcription factors) and develop tools (rapid screening assays, genetic engineering methods and tools such as RNA silencing and CRISPR editing) to facilitate discovery and its application (Rizvi et al, 2016; Mortensen et al, 2019).  If cell and tissue cultures are used as the production platform, growth and defense can be decoupled and optimized independently in a bioreactor setting.  In summary, we seek to understand how the cell regulates the production of its valuable natural products and then apply synthetic biology tools and bioprocess strategies to engineer increased production of these products from either plants or plant cell and tissue cultures.

Announcement: opening for graduate researchers!

This specific project involves investigating the network of transcription factors that regulate the biosynthesis of medicinal alkaloids from the C. roseus plant and developing novel CRISPR tools towards engineering the improved production of these valuable compounds in transgenic tissue cultures.  Aspects of the project involve modular cloning, gene expression analysis, metabolite analysis, genetic engineering, and aseptic tissue cultures.  We are recruiting candidates with relevant background and experience either in molecular biology, biochemistry, or bioengineering!  Contact ca.lee@northeastern.edu if interested.