We perform translational infection research to improve prevention, diagnosis and treatment of human infectious diseases. Our multidisciplinary research teams integrate clinical and basic researchers. Together, we strive to channel knowledge arising from basic research into clinical practice, and also to translate clinical observations into an improved understanding of disease mechanisms.
Infection medicine presents a variety of challenges and medical needs. Infections with multi-resistant bacteria constitute a particularly threat. Furthermore,viral infections can often not be treated effectively. At the same time, the number of patients with increased infection susceptibility is increasing. Such patients include newborns and elderly indivuals, who have an immature or senescent immune system, respectively. Additionally, innovative therapies such as transplantation and treatment with immunosuppressive drugs are used more broadly, which also enhances the proportion of susceptible individuals.
At TWINCORE we develop research projects on the basis of clinical observations and clinical challenges. We focus on the analysis of infections of the gastrointestinal tract, the liver, the lung, and the central nervous system. We pay particular attention to the analysis of patients with enhanced vulnerability to infectious disease, such as newborns and the elderly. We carry out research in multidisciplinary teams which often include the clinicians treating the patients.
Innovative analytics are the basis for an improved infection management. In order to obtain more comprehensive information about disease causing microbes in the shortest time possible, we search for innovative ways of fast and reliable detection and phenotyping of pathogens.
We screen compound libraries in order to identify new candidates that inhibit bacterial and viral pathogens, modulate immunity, or enhance vaccine responses. The Helmholtz Centre for Infection Research (HZI), which is one of the founding partners of TWINCORE, has extensive expertise in the isolation, synthesis and optimization of natural compounds. In our search for new anti-viral and anti-bacterial candidates, we screen the compound library of the HZI and we elucidate metabolic pathways that are affected by the new candidates.
Although in clinical practice many infections can be diagnosed reliably,it is often difficult to predict the clinical course of an individual patient. By analyzing many patients with similar infectious diseases, so called cohort studies, we can learn more about pathogenesis and factors that affect clinical course and outcome. Additionally, by analysing of patients treated with the same drug valuable information about the mode of action, efficacy, and adverse effects of the drug within the human body can be retrieved.
Vaccination is the most efficient way to prevent infectious diseases and even to eradicate pathogens, as exemplified by the eradication of the pox virus. Despite these impressive examples of success, it is still unclear why certain vaccines do not induce protection in certain individuals, and why it is so difficult to develop vaccines against some pathogens. Despite the development of new antiviral compounds, the efficient control and eradication of pathogens at the human population level can only be achieved by vaccination. Multidrug resistant bacteria, too, are vulnerable to attacks by the immune system. Therefore, in addition to new antibiotics innovative vaccines are a promising strategy for the treatment of infections with multidrug resistant bacteria.
Since pathogenesis studies are mostly carried out in animal models, we know comparably little about the development of infectious diseases in humans. However, a detailed understanding of the molecular mechanisms is needed in order to develop new diagnostic approaches, new biomarkers, and new preventive and therapeutic strategies against infectious diseases. In particular, chronic virus infections and lung infections constitute major clinical challenges. Surprisingly little is known about how the balance between pathogen attack and tissue damage is maintained while the immune system is defending tissues such as the gut, liver, lung and the central nervous system against invading pathogens.
Before new intervention strategies can be tested in patients, a plethora of in vitro studies and animals experiments have to be carried out in order to address mode of action and tolerability of the intervention. We study the pathogenesis of selected infections and develop predictive in vitro test systems and animal models.
Chronic viral infections constitute a major clinical challenge. While in the case of infections with chronic hepatitis C virus (HCV) the pathogen can be easily eliminated by treatment with combination drugs, in case human immunodeficiency virus (HIV) infections innovative therapies can only control, but not eliminate, the pathogen. Similarly, a lifelong latent infection establishes upon infection with human cytomegalovirus (HCMV) ; under conditions of immune suppression it can reactivate and then cause severe disease. Protective vaccines are available neither for HCV, HIV or HCMV.
Along with infection of the gastrointestinal tract and the liver, respiratory infections count among the most frequent causes of hospital admissions. We are studying why some individuals are more susceptible to respiratory infections. Moreover, we are searching for novel therapeutic approaches for respiratory tract infections and for biomarkers for early diagnosis and prediction of disease severity. Moreover, we are studying bacterial strategies to evade therapies.
Immune responses are usually induced in secondary lymphoid organs, while the effector function of antigen-specific immune cells can also manifest locally within the infected tissue. Of note, tissue cells modulate the activity of locally active immune cells in order to minimize tissue damage during pathogen attacks. Although these mechanisms are of great clinical importance, they remain only partially understood.
In many cases not the pathogen itself, but the exuberant inflammatory reaction, causes severe disease. Latest observations imply that interfering with the cellular metabolism of immune cells can dampen local inflammatory immune reactions. We study compounds that target the immune metabolism and thus have the potential to modulate inflammatory responses in organs such as the gut.