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Kevin and Mike Fedkenheuer

Mike and Kevin Fedkenheuer infiltrating Nicotiana benthamiana, in John McDowell's lab.

Rushing evolution

 

Millions of dollars of crop loss in the United States and billions of dollars worldwide can be attributed to Phytophthora sojae, a deadly plant pathogen attacking soybeans.
 

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.”
 

 

Q&A: Meet Kevin and Mike

Hometown: Both: Norwood, NJ
Degree: Both: Ph.D. Plant Path, Phys & Weed Science (PPWS)
Other Degrees: Both: James Madison University, B.S.Biotechnology, Minor: Chemistry;  Mike: M.S. Life Science and Biochemistry at Virginia Tech
 
 

What attracted you to your particular field of science?

 
Kevin: My James Madison University advisor, Dr. Temple, recommended to me that I should get some experience doing research in the beginning of my Junior year as an undergraduate. Soon after, I joined Dr. John Monroe’s lab at JMU. My research was focused on enzymes involved in starch degradation in plants. After a couple months I knew that I wanted to pursue a future degree in plant sciences.
 
Mike: I am attracted to many fields in science. What made studying plant pathology attractive is the opportunity to study the constantly evolving battle between host and pathogen. Seeing the fruits of my efforts in the form of a disease resistant plant will allow me the satisfaction of seeing the real world application of my work.
 

Which quality of the following do you feel is the most important for a scientist to possess—open-mindedness, precision, time management skills, optimism, cynicism, integrity, a good sense of humor? Why?

 
Kevin: Open-mindedness. If we are too afraid to try new things, then we will never be able to advance our field for future work.
 
Mike: A good mix of all of them is important; however perhaps the most important is not listed, courage. To make a real impact in science you have to jump into the unknown and take chances, the word impossible should not be in your vocabulary. Some of the greatest advances in science have come from what can be called a “leap of faith.” Thus, you need to be strong enough to stand by your ideas, but also be strong enough to admit when you’re wrong as well.
 

Which type of science, other than what you study, interests you most?

Kevin: Cancer research because there are so many new advancements and new technologies. I am always blown away by the cutting edge ideas in this field.
 
Mike: Virology. My first undergraduate project at JMU was working with components of the Dengue Virus protein. I thought it was amazing how this virus was actually more virulent upon a secondary exposure. This is contrary to everything I have learned about immunity because it uses host antibodies to expedite its entry into cells. Viruses have a myriad of uniquely developed tools which make them extremely interesting to study as well as providing us with new molecular tools we can steal for treating disease and developing new techniques.