College of Natural Sciences

The challenge of genetically modifying hops plants to produce more of a potentially effective cancer-fighting compound brought a researcher from Belgium to work with Axel Schwekendiek, assistant professor of biology.

Lina Maloukh, a doctoral student at the Institute for Agricultural and Fisheries Research in Belgium, had isolated critical genes from hops, but needed a transformation system to test the genes. Transformation is the genetic modification of a cell by the introduction of foreign genetic material.  Schwekendiek has spent eight years perfecting a transformation system for hops.

Schwekendiek and Maloukh, as well as other collaborators in the U.S., Canada, and Europe, are interested in xanthohumol, a compound that is naturally occurring in hops, the herb that gives beer its main flavor.  One of the compound's many uses, according to Schwekendiek, is that it inhibits tumor growth.  Unfortunately, because the amount of xanthohumol in hops is low, a person would have to drink 17 beers a day to get any benefit, he said.

 

A petri dish with hop tissue explants developing into undifferentiated callus cells. The green pieces--developing and growing tissues--are transferred every other week to fresh media to support further development into an entire hop plant.

If the amount of the compound can be increased, it can be extracted and used, say, in the form of a pill, Schwekendiek said.   But because 98% of hops go for beer production, there is a shortage of hops, and hops with a higher level of xanthohumol are needed for pharmaceutical research. 

 

That's where Schwekendiek's research project comes in.  For eight years he has been working to develop a transformation system to genetically engineer hops.  This is a time-consuming process because the genes must be inserted into the plant’s cells and expressed so they can function in the plant.  But his system has been tested several times and works well.  In this case, Schwekendiek and Maloukh use the hops' own genes to make more xanthohumol.

 
An understanding of biosynthesis--how the plant makes the compound--is another important aspect.  The researchers need to know which proteins and which genes affect the production.  This research is part of a larger collaboration, being funded in part by an international company that breeds and grows hops.  Canadian researchers are working on the biosynthesis aspect of the problem.

The researchers are still missing two important genes, but there are several other options.  During Maloukh’s Ph.D. work, she and a collaborator from the Czech Republic isolated from hops a few genes from the pathway leading to

In the semi-automated temporary immersion system, developed by UNI student Scott Hanson and used in Schwekendiek's lab, hop tissue explants are maintained on a mesh and flooded every couple of hours with liquid nutrient containing media.

xanthohumol.  These genes are now used in Schwekendiek’s lab to genetically engineer hops.  Since Schwekendiek’s group, together with his former lab in Germany, is one of the few groups worldwide that can transform hops, Maloukh came to Iowa to carry out the technique.  She provided the genes that are essential to enhance the content of xanthohumol in the hops.

 

The collaboration of teams of researchers in the U.S., Belgium, Canada, the Czech Republic, as well their industrial partner, Hopsteiner, has worked well, according to Schwekendiek, because everyone is working toward the same goal and contributes expertise to the project.

 

Schwekendiek and Maloukh presented their findings in September 2008 at the Hop Symposium. Schwekendiek focused on recent improvements in the efficiency of the hop transformation system, and Maloukh presented work on gene identification and cloning and the transformation being carried out at UNI.

 

In continuing his work, Schwekendiek plans to involve more undergraduate and graduate students in his genetic transformation efforts.  In the summer of 2008, he sent two UNI students who had worked on the project in his lab to work at Hopsteiner in Yakima, Wash.  Because of their experience with hop research, they were involved in laboratory management and data collection from the hop breeding program being carried out there.

 

Following is a selected list of publications related to the work discussed above, as well as Schwekendiek's e-mail address.

 

---

Gerhauser C., Alt, A., Heiss, E., Amira, G.-E., Klimo, K., et al. (2002).  Cancer chemopreventive activity of xamthohumol, a natural product derived from hop.  Molecular Cancer Therapeutics, 1, 959-969.

Horlemann, C., Schwekendiek, A., Hohnle, M., & Weber, G.   (2003). Regeneration and agrobacterium-mediated transformation of hop (Humulus lupulus L.).  Plant Cell Rep., 22 (3), 210-217.

Maloukh, L., De Keukeleirea, J., Matousekc, J., Matthews, P.D., Schwekendiek, A., et al.  (2008). Functional characterization of genes controlling the production of bioactive prenylflavonoids in hop (Humulus lupulus L.).  Submitted for publication to Acta Hort. (ISHS).

Schwekendiek, A., Hanson, S.T., & Crain, M.  (2008).  A temporary immersion system for the effective micropropagation of hop.  Submitted for publication to Acta Hort. (ISHS).

Schwekendiek, A., Spring, O., Heyerick, A., Pickel, B., Pitsch, N.T., et al. (2007). Constitutive expression of a grapevine stilbene synthase gene in transgenic hop (Humulus lupulus L.) yields resveratrol and its derivatives in substantial quantities.  J. Agric. Food Chem., 55 (17), 7002-7009.

Schwekendiek, A., Horlemann, C., Spring, O., Stanke, M., Hohnle, M., et al.  (2005).  Hop (Humulus lupulus L.) transformation with stilbene synthase for increasing resistance against fungal pathogens.  Acta Hort. (ISHS), 668, 101-108.