Protein Biomarker Unit

Protein Biomarker Unit
© Fraunhofer IZI


The Protein Biomarker Unit focuses on the identification and validation of proteins to be used as diagnostic biomarkers or representing therapeutic targets. Moreover, the unit aims at the development of single and multiplex assays for their detection. Multi-omics strategies (especially LC-MS based proteomics) are applied for identification. ELISA, western blot, and peptide or bead arrays (Luminex) are utilized for validation. High-affinity monoclonal antibodies, which are usually developed in the group, are key tools for these immunochemical assays.


Prof. Dr. Stefan Kalkhof also holds the research professorship for the master degree program Bioanalytics at the Coburg University for applied science and arts. This synergy enables the identification and characterization of relevant biomarkers by mass spectrometry, which are then validated in the Department of Therapy Validation using antibody-based techniques and prepared for clinical application.

Improving hookworm monitoring through the development of a rapid diagnostic test (“WormShield”)

The Ancylostoma caninum hookworm attached to the intestinal mucosa
© CDC’s Public Health Image Library

Worm infections still present a major health-related challenge, especially in tropical and sub-tropical regions. According to statistics published by the Centers for Disease Control and Prevention in 2013, more than 700 million people around the globe are affected by hookworm infections alone, which cause up to 60 000 deaths per year. The infection is transmitted upon coming into contact with water or soil that has been contaminated with feces, which means that it mainly affects rural populations. The infection can be treated effectively with albendazole or mebendazole. The diagnostic methods used at present (Kato Katz, MiniFLOTAC, McMaster) require trained staff and a suitable diagnostic infrastructure, which is why many infections are not diagnosed until very late.

The aim of the international collaboration project “WormShield”, which sees the Protein Biomarker Unit collaborate with the company BioScientia (Poland), Cayetano Heredia University (Peru) and Dr. Hugo Mendoza Pediatric Hospital (Dominican Republic), is to improve the diagnosis of hookworm infections in an everyday clinical setting by developing a quick, specific, sensitive, robust and easy-to-use lateral-flow assay. This test is then to be rolled out around the world as a point-of-care diagnostic tool.

The project is being funded by the EU as part of the EU-LAC Health initiative to promote cooperative health research with states from Latin America and the Caribbean.

Project manager
Prof. Dr. Stefan Kalkhof

LowAllergen / FoodAllergen – Detection of plant-derived allergenic protein structures with subsequent modification and testing for the successful reduction of allergenic potential through analytical methods

The frequency of newly developed food allergies (incidence) is increasing worldwide. At the same time, a rise in non-conventional food ingredients – particularly plant-based ingredients – has been registered, following the modern trend of resource-conscious food. This trend has also been noted by European directives with the purpose of making consumers aware of the risk of allergies as well as protecting them from the consequences of allergies (LMIV). As a result, the demand for reliable methods to analyze allergenic ingredients as well as for the technology to reduce allergenic ingredients has grown significantly over the past few years.

The "LowAllergen" project and its follow-up project, "FoodAllergen", are concerned with plant-based allergenic food ingredients. One part of the project is geared towards changing proteins to the extent that their allergenic potential is decreased. The requirements for this are innovative technologies for modifying proteins which are developed in our partner institute Fraunhofer IVV. As part of the “Food Allergen” project, the Protein Biomarker Unit is responsible for developing antibody-based test systems which enable a quantitative analysis of allergenic ingredients and reveal any remaining allergenic potential after applying allergen-reducing procedures. Using soy as an example, in the "LowAllergen" project, a decrease of allergenic components could be observed as a result of applying certain microorganisms in fermentation processes and hydrolysis using high pressure. In the "FoodAllergen" project, the processes and analytical methods will be expanded to other plant-based protein ingredients to implement technologies for modifying allergens as well as analytical methods for detecting successful reduction of allergens as soon as possible.

Project manager
Dr. Elke Ueberham

Development of diagnostic assays for detection of biomarkers in milk and blood for health control in dairy herds

In the field of ‘Biomarker-based veterinary diagnostics’ specific and sensitive diagnostic techniques based on immunological biomarkers are going to be developed for cattle. Screening tests verifying biomarkers are particularly appropriate to detect sick animals within the herds prior the occurrence of clinical symptoms. Positively diagnosed animals could supply veterinary examination in a targeting manner. Potentially, this approach could result in a medium-term increase in economic efficiency. Because animals’ health and well-being are closely related the development of biomarker tests contributes considerably to the principles of animals’ and consumers’ welfare.

In the project ‚On-Farm-Recording_Breeding‘ supported by the (former) Federal Ministry of Food, Agriculture and Consumer Protection, the Department of Therapy Validation has identified and characterized different biomarkers for health monitoring in cattle. A patent application submitted in 2015 is aimed at an international patent protection. The best performing biomarker candidates are currently under pre-commercial development at different stages. The final steps to reach marketability will be done in close collaboration with our industrial partners. A substantial benefit for the optimal diagnostic value is expected from the combined detection of biomarker through multiplex analysis. Together with partners in veterinary medicine, livestock breeding farms, and diagnostics industries we aim at the development of user-friendly products that will be well-accepted by farmers. Moreover, we seek to offer innovative product concepts that will suit the needs of a future-compliant agriculture.

The diagnostic assay for the detection of haptoglobin, a major acute-phase protein in cattle, is currently at the last stage of pre-commercial development, i.e. clinical validation. For the development of diagnostic assays for further interesting biomarker candidates we are searching for granting opportunities.

Project manager
Dr. Anke Hoffmann, Dr. Jörg Lehmann

Completed projects

  • Project "Bronchial Carcinoma" as part of the BMBF program "Innovative Regional Growth Cores", "GC Potential" module

  • Wuchty S, Müller SA, Caufield JH, Häuser R, Aloy P, Kalkhof S, Uetz P. Proteome data improves protein function prediction in the interactome of Helicobacter pylori. Molecular & cellular proteomics 17 (2018), Nr.5, S. 961-973. dx.doi.org/10.1074/mcp.RA117.000474
  • Havenith H, Kern K, Rautenberger P, Spiegel H, Szardenings M, Ueberham E, Lehmann J, Buntru M, Vogel S, Treudler R, Fischer R, Schillberg S. Combination of two epitope identification techniques enables the rational design of soy allergen Gly m 4 mutants. Biotechnology journal 12 (2017), 2, Art. 1600441, 10 S. dx.doi.org/10.1002/biot.201600441
  • Meinlschmidt P, Brode V, Sevenich R, Ueberham E, Schweiggert-Weisz U, Lehmann J, Rauh C, Knorr D, Eisner, P. High pressure processing assisted enzymatic hydrolysis - An innovative approach for the reduction of soy immunoreactivity. Innovative food science & emerging technologies 40 (2017), S. 58-67. dx.doi.org/10.1016/j.ifset.2016.06.022 
  • Meinlschmidt P, Ueberham E, Lehmann J, Schweiggert-Weisz U, Eisner P. Immunoreactivity, sensory and physicochemical properties of fermented soy protein isolate. Food Chemistry. 2016 Aug 15;205:229-38. dx.doi.org/10.1016/j.foodchem.2016.03.016. Epub 2016 Mar 8.
  • Meinlschmidt P, Ueberham E, Lehmann J, Reineke K, Schlüter O, Eisner P, Schweiggert-Weisz U, Knorr D. Application of nonthermal technologies for the mitigation of soy immunoreactivity – pulsed ultraviolet light, - irradiation, and nonthermal atmospheric plasma. Innovative Food Science and Emerging Technologies 2016
  • Zoldan K, Moellmer T, Schneider J, Fueldner C, Knauer J, Lehmann J. Increase of CD25 expression on bovine neutrophils correlates with disease severity in post-partum and early lactating dairy cows. Dev Comp Immunol. 2014 Aug 11;47(2):254-263. dx.doi.org/10.1016/j.dci.2014.08.002. [Epub ahead of print]
  • Wege AK, Schmidt M, Ueberham E, Ponnath M, Ortmann O, Brockhoff G, Lehmann J. Co-transplantation of human hematopoietic stem cells and human breast cancer cells in NSG mice: a novel approach to generate tumor cell specific human antibodies. MAbs. 2014 Jul-Aug;6(4):968-77. dx.doi.org/10.4161/mabs.29111. Epub 2014 May 8
  • Fueldner C, Mittag A, Knauer J, Biskop M, Hepp P, Scholz R, Wagner U, Sack U, Emmrich F, Tárnok A, Lehmann J. Identification and evaluation of novel synovial tissue biomarkers in rheumatoid arthritis by laser scanning cytometry. Arthritis Res Ther. 2012 Jan 17;14(1):R8. dx.doi.org/10.1186/ar3682