We believe that it is our responsibility as researchers to try to uncover phenomena that can be used to solve global problems. Problems like how to produce enough food to feed the growing human population and how to produce medicines needed to prevent or treat major diseases. As biologists with expertise in plant metabolism, we focus to understand the genetics of how plants produce specialized metabolites that function to minimize yield loss caused by pathogens, pests, and climate change, and metabolites that have medicinal properties.
Stress response - The regulation of phytoalexin synthesis in plants
Phytoalexins are defense metabolites that are synthesized in plants in response to pathogens and particular environmental stresses. Glyceollins are the major phytoalexins produced by the soybean plant. Glyceollins have broad-spectrum anticancer and neuroprotective activities. They also have a major role in defending soybean plants against Phytophthora sojae, a major water mold pathogen that causes 1-2 billion dollars in soybean yield loss per year worldwide. Without a particular stress, plants lack phytoalexins. We are studying the genetics of how plants regulate phytoalexin synthesis focusing on glyceollins in soybean as a model. Enhancing phytoalexin synthesis in plants could generate economical sources of medicines and plants that have greater yields due to their enhanced disease resistance.
Glyceollin I is an phytoalexin with broad-spectrum activity
against cancers and microbial pathogens.
Metabolic engineering - Phytoalexin gene regulatory networks
Transcription factors (a.k.a. TFs) are proteins that regulate when, where, and how much a gene is expressed in a living organism. Our research has demonstrated that multiple TFs are needed to regulate all the genes that synthesize glyceollin phytoalexins. Importantly, other TFs that are required to 'turn on' glyceollin synthesis still remain unidentified. Thus, a network of TFs work together to coordinate the production of glyceollins in soybean.
We are gradually piecing together the network of genes needed to turn on the synthesis of the medicinal/defensive glyceollin metabolites in soybean.
Metabolite transport - How do plants accumulate massive amounts of chemicals?
A major limitation that is hindering our ability to engineer plants that can accumulate massive amounts of specialized metabolites is the lack of understanding of how those metabolites are targeted for storage or excretion (moving out of cells) after they are synthesized. We are using plant pigmentation as a read-out to begin to identify genes that are involved in metabolite transport processes.
Arabidopsis plants under an environmental stress condition normally produce high amounts of a purple pigment called anthocyaninss (WT). A mutant plant deficient in the synthesis of the hormone abscisic acid does not turn on as much pigment synthesis (aba2-1). A transporter gene mutant that is affected in abscisic acid distribution has altered pigmentation compared to normal (abc).
Bioactivity - Enhancing the medicinal activities of natural molecules
It is common that natural metabolites do not have potent or specific enough medicinal activities in human cells to render them appropriate for clinical use. However, minor changes in their chemical structure can impart more potent and specific medicinal activities. For this reason, we developed an approach to modify the structure of natural metabolites that can then be tested for increased anticancer activity compared to their parent metabolites.
Engineered plants and microorganisms can be combined with test-tube chemistry to modify the structure of anticancer natural products to produce derivatives with enhanced bioactivities.