NSF award aids Basset's coenzyme Q research

NSF award aids Basset's coenzyme Q research
Nearly all organisms — from animals and plants to many bacteria — require the micronutrient ubiquinone, or coenzyme Q, for survival. Humans produce it in their bodies and consume it in their diets. But scientists don’t understand how cells produce this vital compound.

Gilles Basset, an assistant professor of agronomy and horticulture, is using a new approach to study this elusive nutrient. His research may lead to improving human health. A faculty member in UNL’s Center for Plant Science Innovation, Basset studies how plants synthesize and metabolize chemicals beneficial to health.

He’s expanding his ubiquinone research with a five-year, $784,820 Faculty Early Career Development Program, or CAREER Award, from the National Science Foundation. This prestigious award helps outstanding pre-tenure faculty develop as teacher-scholars and researchers.

“We know that they are very important, but we don’t understand how living organisms make these compounds,” Basset said of ubiquinones. “Understanding how they are made will allow us to, for instance, improve plant-based food.”

Ubiquinone compounds, named for their ubiquitous presence in organisms, are key ingredients in the movement of electrons and protons. That movement converts glucose into energy within mitochondria, cells’ power supply centers, and are necessary for cellular respiration.

But these compounds are so fragile and present in such small amounts that conventional biochemical and genetic approaches to studying molecules can’t reveal many important aspects of their production.

To help reveal these secrets, Basset is using bioinformatics, an increasingly important research approach that harnesses computing methods to explore complex biological questions.

He’s using metabolic reconstructions and comparative genomic data mining to identify the genes involved in ubiquinone synthesis. Data mining uses computers to look for associations within the entire genetic makeup of different types of organisms. Organisms that synthesize ubiquinone should have genes in common that are missing in those that don’t. Additional techniques further narrow the list of gene candidates by identifying similarities in how genes are expressed.

“We decided to combine all of the genomic information from hundreds of organisms,” Basset said. “When you examine all the organisms together, patterns start to appear that were invisible in a single organism. Then we can reconstruct the evolutionary story of the genes and the biosynthetic pathways they are involved in.”

Understanding ubiquinone synthesis, as well as other challenging quinones such as vitamin K, may lead to better understanding deficiency-related diseases and to better prevention and treatment strategies.

For example, Basset’s team recently discovered a plant enzyme involved in ubiquinone biosynthesis. Mutations in the gene that codes for the same enzyme in humans may lead to a rare genetic muscular degenerative disease once thought incurable because the gene’s function was previously unknown. Researchers now believe the disease is caused by a lack of coenzyme Q10, the human ubiquinone, and may be cured with a simple supplement.

Basset’s research also may help improve nutrition. Eating a balanced diet typically provides the vitamins and other micronutrients healthy human bodies require. But many people no longer eat enough fruits and vegetables, which can result in health problems caused by nutrient deficiencies, Basset said.

In addition, the grains that feed most of humanity, such as wheat, corn and rice, contain few vitamins and minerals. In the U.S. and Canada, vitamins and nutrients are added to some breakfast cereals and other foods made from grains, but processed foods aren’t available in some countries.

By understanding how plants make vitamins and other quinones, scientists could breed or genetically transform plants to increase their nutrient levels, Basset said.

Although comparative genomic data mining has become an important scientific tool, few students have the opportunity to learn and use it. Basset aims to change that. With support from this grant, he is creating a web-based resource for students and instructors and will promote bioinformatics data mining instruction nationwide. He also is continuing to raise awareness of micronutrients and good dietary habits through an educational program for schoolchildren.