Taxol is a secondary metabolite, produced by the plant as a means of defense against predators. Secondary metabolites prove useful to humans in a variety of ways, so a deeper understanding of how plant cells synthesize them could be highly advantageous.
“Our general work in secondary metabolism will have influence not just in health but in energy and agriculture,” Roberts explains.
Due to slow growth and low yields, secondary metabolites such as Taxol often cannot be extracted directly from the plant in large enough quantities. Roberts is developing an alternate supply method using cell culture and demonstrating how biotechnology and bioprocessing can be applied in the laboratory to enhance productivity. In nature, environmental factors trigger the expression of genes that regulate the synthesis of secondary metabolites. A nearby predator, among other threats, gives off chemicals that activate a response within the plant. The resulting secondary metabolites are intended to eliminate the threat and are often toxic to cells, which makes them useful in treating human ailments such as cancer. Cancer cells divide rapidly, yet Taxol binds to the microtubules responsible for cell division, causing the cancer cell to freeze and ultimately die.
“Plants need to have a very sophisticated defense system… they can’t get up and run away if something is attacking them. They will produce these compounds that will essentially invade and destroy predators...it’s a really complex system in nature that we can replicate in the laboratory,” Roberts explains.
Using Taxus suspension cultures in the lab, Roberts and her research team are experimenting with biotic elicitors to identify which chemicals in the environment trigger the appropriate gene expression in culture that results in increased yields of Taxol. Roberts and her team are also employing state-of-the-art techniques in sequencing, bioinformatics and metabolic engineering to identify and eventually manipulate the genes that regulate production of secondary metabolites—work they are doing in collaboration with the Boyce Thompson Institute at Cornell University. The collaborative team is developing methods to modulate gene expression in cell culture and whole plants to produce higher, or lower, yields of particular secondary products. For example, lignin, a chemical component in cell walls, is also a secondary metabolite. The capacity to manipulate the production of lignin would be extremely valuable in biotechnology and agriculture, as it would allow scientists to influence the performance of the cell wall.
Roberts and the team are also conducting research around cellular aggregation. Roberts explains how in culture, plant cells cluster together in a variety of ways. The team is finding that aggregation influences both culture performance and production of the desired compound.
“We have shown in the last couple of years that the extent of aggregation directly correlates with the amount of Taxol in a culture. We’re really trying to fundamentally understand the whole process of aggregation in culture, so that we can effectively manipulate aggregation dynamics to influence culture performance,” says Roberts.
Roberts’ team is also working to design the optimal environment in which cells can grow and function. Roberts says that this “mechanical and chemical” environment has a considerable impact on how cells behave. Critical to this research is the ability to measure the microenvironment—the area around each individual cell. Roberts and the team are collaborating with Alfred Crosby in Polymer Science and Engineering to design a new method to quantify that environment and measure its impact on cell function.
“I don’t think the technology has been there, quite yet, to be able to define what this environment is. I think the new tool that we’re applying to natural polymer systems developed by the Crosby lab, cavitation microrheology, will finally be able to get at what that environment around an individual cell or cell aggregate looks like,” says Roberts.
As both a professor and the director of the Institute for Cellular Engineering, Roberts has always been passionate about integrating the life sciences into engineering. She finds it important to conduct research that has an element of translation, and that serves a purpose within the community.
“There’s a societal need that motivates my research. Being able to design new methods for synthesizing pharmaceuticals, or designing new devices to support cell growth for tissue engineering is very rewarding. We need to get more students to see the outcomes of their fundamental work,” Roberts says.
Susan Roberts’ team is working to design the optimal environment in which cells can grow and function. Understanding how cell behavior is controlled can lead to breakthroughs for the pharmaceutical, biotechnology and medical device industries, says Roberts.