Our research projects focus on antimicrobial peptides, post-translational modifications, proteomics and peptide synthesis, as well as other research topics based on our established technologies.
Current research projects
Development of innovative multiplex diagnostic methods for the detection of viral and bacterial infections in laboratory animals based on highly immunogenic proteins
The health status of laboratory animals is checked in Europe according to the recommendations of FELASA. This involves quarterly and annual testing against 24 pathogens, with the aim of detecting acute, persistent and already overcome bacterial and viral infections (i.e. pathogen no longer detectable). Therefore, diagnostic applications targeting the pathogen, i.e. genetic (e.g. PCR) or mass spectrometric test methods are not sufficient, but must be complemented by serological methods such as ELISA (Enzyme Linked Immunosorbent Assay) and IFT (Immunofluorescence Test). Due to the fact that tests based on complete virus particles or bacterial lysates have not yet been standardized, there is a considerable risk of false-positive and false-negative findings in practice. Furthermore, a separate test has to be performed for each pathogen, which means an enormous amount of work and costs and at the same time requires a high consumption of biological material.
The aim of this research and development project is the identification and expression of highly immunogenic proteins of several bacteria and viruses with subsequent identification of the epitopes. Specifically, bacterial proteins will be separated by gel electrophoresis (SDS-PAGE and two-dimensional PAGE) and immunogenic proteins recognized from sera of infected animals will be identified by mass spectrometry. These bacterial proteins and selected proteins of some viruses would be recombinantly expressed to develop a sensitive ELISA. In the end, the pathogen-specific proteins would be combined on an array to develop a serological multiplexing assay that requires only small amounts of serum and allows for extremely cost- and time-efficient diagnostic applications.
Optimierung, Generierung und Pharmakokinetik optimierter Oncocin- und Apidaecin-Analoga
Although many bacterial infectious diseases can be treated well with antibiotics today, the massive spread of multi-resistant and especially pan-resistant Gram-negative bacteria poses an increasing health risk with rising lethality. In particular, these life-threatening germs spread in hospitals and nursing wards (nosocomial infections), i.e. within a ward via staff and visitors and between hospitals via patient transports and visitors. Antimicrobial peptides (AMPs), which are structurally derived from naturally occurring substances of a wide variety of organisms, are a promising class of potential new agents.
In recent years, we have optimized proline-rich AMPs (PrAMPs) from different organisms for their potential to treat human pathogens and have already successfully tested some promising representatives in infection models. Based on this long-term experience, the existing lead structures will be further developed and evaluated microbiologically, pharmacokinetically, pharmacodynamically and via their activity in infection models, especially for the treatment of pneumonia resulting from (short-term) artificial ventilation (nosocomial ventilator-associated pneumonia, VAP). Specifically, the most common pathogens of VAP will be addressed, i.e. Pseudomonas aeruginosa (24% of all infections), Staphylococcus aureus (20%), Enterobacteriaceae (14%) and Acinetobacter baumannii (8%). At the same time, possible resistance mechanisms of the bacteria will be identified and elucidated to assess their potential in the clinic.
Innovative live AMP phage agents for the cost-effective treatment of infectious diseases of domestic animals as a biological and environmentally safe alternative to the use of antibiotics
The use of antibiotics has led to a considerable selection of multidrug-resistant bacteria in both human and veterinary medicine, which cause complications with increasing lethality, especially in hospitalized patients (nosocomial infections). While the treatment of larger groups of animals with antibiotics in livestock production is subject to strong criticism, little attention is paid to the antibiotic treatment of small animals and horses. However, selection of nosocomial multidrug-resistant bacteria also occurs in small animal and equine clinics. In the event of a therapeutic emergency, reserve antibiotics from human medicine are used in many cases in veterinary clinics. Many of these pathogens and thus their resistances can be transferred to humans. An important example of this problem is infections of horses with multi-resistant Salmonella. This important zoonotic pathogen occurs frequently in horses in equine clinics. Since antibiosis often fails to eliminate the pathogen, these animals can become a source of human infections after discharge as excretors. Highly problematic in horses is the global spread of multidrug-resistant Salmonella enterica serovar Typhimurium phage type DT104 since 1990 and Salmonella enterica serovar Kentucky ST198, which is highly resistant to the reserve antibiotic ciprofloxacin. In view of these boundary conditions and the massive spread of resistant bacteria in the human and veterinary sector, a new, innovative biological approach with "living agents" will be tested here. In this approach, phages penetrate the resistant bacteria, multiply in them and replicate antibacterially active substances locally in the animal according to the individual degree of infection (bacterial count). To this end, the effect of bacteriophages, i.e. viruses that specifically recognize and kill bacteria, is to be tested in vitro on various bacterial cultures and under different conditions.
The research project is funded by the European Union from the “European Regional Development Fund”. This measure is co-financed by tax funds on the basis of the budget adopted by the members of the Saxon Parliament.
Epitope-specific study of SARS-CoV-2 infection as a prognostic tool and basis of vaccine development
Betacoronavirus (CoV) can cause epidemic respiratory infections, such as severe acute respiratory syndrome (SARS) and the currently observed SARS-CoV-2 variant pandemics. Based on recombinant structural proteins of SARS-CoV-2, we aim to identify the major immunogens in covid-19 patients and the post-August 2020 population and to detect cross-reactivities in the general population by direct comparison over control samples collected before 2019. This will allow estimation of ELISA specificity for different age groups and for individual pre-existing conditions. Peptide arrays will also be used to identify linear B-cell epitopes and, like proteins, will also be tested for sensitivity and specificity. The protein ELISA and the identified epitope sequences will be used to determine antibody titers in serum samples from COVID-19 patients with mild and severe symptoms to provide evidence of a favorable or unfavorable immune response.
Diagnose and prognose of type 2 diabetes in early and prediabetes stadium
Diabetes mellitus is a metabolic disease characterized by chronically elevated blood glucose levels. With 6.5 million diagnosed diabetics, Germany ranks second in Europe. Approximately 95 percent of those affected suffer from type 2 diabetes mellitus (T2DM). Although T2DM is not initially perceived as a "real disease" by those affected, the diabetes-associated comorbidities and secondary diseases that occur later contribute significantly to a reduced quality of life and a significantly increased mortality rate. Alarmingly, approximately 2 million people in Germany suffer from undiagnosed T2DM, mainly due to the low sensitivity (< 55%) of screening methods (fasting blood glucose & HbA1c). As a result, 37% of type 2 diabetics are not detected in time.
In the search for new biomarkers for the early and sensitive diagnosis of T2DM and for monitoring the progression of the disease based on the underlying pathological changes, we have found them in the glycation of certain proteins in the blood. Our marker HPK141 (glycated haptoglobin) identifies T2DM at first diagnosis in combination with HbA1c with an excellent sensitivity of 98% (current screening: < 55%) and 96% in combination with "circulating free fatty acids". In addition, it detects half of all prediabetics, allowing early initiation of non-drug baseline therapy. Other biomarkers we have identified differentiate T2DM and prediabetes into three groups, each with its own individual disease progression. The project will develop sensitive assays for several of the identified biomarkers in serum samples to maximize sample throughput for clinical diagnostics. Once the assays are validated, the biomarkers will be validated in larger cohorts for use in the early diagnosis of type 2 diabetes or prediabetes.
This measure is co-financed by tax money on the basis of the budget approved by the Parliament of Saxony.
We are always open for cooperation projects with academic working groups within and outside Leipzig University as well as with companies.