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Mike and Kevin Fedkenheuer infiltrating Nicotiana benthamiana, in John McDowell's lab.
Twin brothers and Ph.D. students, Kevin and Mike Fedkenheuer are working in John McDowell’s lab with Phytophthora sojea and Hyaloperonospora arabidopsis, oomycete pathogens, to examine their molecular genetics and how they alter the immunological responses of soybean cultivars, Arabidopsis thaliana and other bean species.
Oomycete pathogens contain effector proteins that suppress the plants immunological response and ability to fight off the pathogen. The pathogen infects the plant and secretes its proteins. However, in certain instances the plant identifies these effector proteins and is then able to defend itself from the pathogen. The Fedkenheuers are trying to determine which novel resistance genes make the plant able to identify effector proteins and determine the structural domains of these proteins recognized by the host. Ultimately, they would like to use this information to engineer resistance genes into the plants’ seeds.
Kevin Fedkenheuer has worked with McDowell, an associate professor of plant pathology, physiology, and weed science in the College of Agriculture and Life Sciences and an affiliated faculty member with the Fralin Life Science Institute, for two years and is progressing toward engineering a transgenic seed of elite soybean cultivar that is resistant to the P. sojea pathogen. He does this through a process called effector directed breeding. Effector directed breeding involves growing hundreds of different soybean cultivars, infecting them with the pathogen, identifying which plants survive and then determining what resistance genes make it able to identify and then fight off the pathogen. Once those novel resistance genes are found he will speed the process of evolution by breeding these genes into the elite soybean cultivar species used by the majority of farmers today.
Concurrently, he is also conducting transcript profiling of A. thaliana plants and the pathogen, H. arabidopsis. This process involves “looking at how all the genes in the plant respond to the pathogen, which will determine its disease susceptibility,” stated Kevin Fedkenheuer. On this project he is collaborating with researcher Brad Day, assistant professor of plant pathology at Michigan State University and Ruth Grene, professor of plant pathology, physiology, and weed science at Virginia Tech.
“Kevin is a very bright and creative student. In only a few months, he set up a system for screening for new pathogen resistance genes, in soybean,” McDowell said. “I recently learned that a large group in China had been trying to set up a similar system for two years without success. Now we are going to collaborate with this group and they are going to use Kevin’s system. Kevin is also bringing new technologies into my lab as part of his second project on transcript profiling.”
Mike Fedkenheuer is in his first year in Dr. McDowell’s lab and working on two projects. Much like Kevin’s first project, Mike conducts effector directed breeding in beans and other legumes. He also hopes to engineer seeds that are resistant to the Phytophthora pathogens.
“The benefit is that these seeds are not considered genetically modified,” he said.
“The genes are already there, we just need to find them and breed them in; we are essentially rushing evolution,” said Kevin.
In Mike Fedkenheuer’s second project he moves away from working with the plant and focuses specifically on the pathogen's conserved effector proteins with P. sojea and H. arabidopsis. Using a process called homology modeling, he seeks to identify the smallest structural domain within the protein that the plant recognizes to trigger an immunological response. A structural domain is a sequence of amino acids within a protein that can function and fold independently without the rest of the protein.
”Finding the domain that is recognized by plants can reap several benefits, such as identifying effectors in other pathogen species or for intelligently designing proteins for plant immunity,” Mike Fedkenheuer said.
“Mike is leveraging his previous training in structural biology and biochemistry to bring a new perspective and skill set to an ongoing project,” McDowell said.
While working on his master’s degree, Mike Fedkenheuer worked in Pablo Sobrado’s lab for the Virginia Tech Drug Discovery Center, where he excelled at x-ray crystallography. This skill gives him an advantage in identifying structural domains in McDowell’s lab. His x-ray crystallography background includes working at Virginia Tech’s Crystallography Laboratory and also at Brookhaven National Labs, NY, in their synchrotron facilities.
“Mike had ‘the magic touch’ for crystallizing proteins,” Sobrado said.
While working in Sobrado’s lab, Mike Fedkenheuer also co-authored two papers: Structural Insight into the Mechanism of Oxygen Activation and Substrate Selectivity of Flavin-Dependent N-Hydroxylating Monooxygenases and Dual role of NADP(H) in the reaction of a flavin dependent N-hydroxylating monooxygenase; and a third is expected to be published soon.
McDowell considers both Kevin and Mike Fedkenheuer assets to his lab. “As twins, it’s clear that Kevin and Mike share a rather unique intellectual synergy, and I’m looking forward to mentoring them in the upcoming years. The only downside is that I’ll have to come up with fresh, witty rejoinders to the barrage of human cloning jokes to which I’ll be subjected.”
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