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The fluorescent dye DAPI is commonly used to stain the DNA in the nuclei of Caenorhabditis elegans body cells, thus visualizing the nematode’s anatomy.

Photo courtesy:
Hinrich Schulenburg

Pathogenic Bacillus thuringiensis bacteria marked by Red Fluorescent Protein have infected and overgrown the body of a Caenorhabditis elegans nematode.

Photo courtesy:
Andrei Papkou, Schulenburg lab

Confocal laser scanning microscopy image of the fungal pathogen Zymoseptoria tritici (in green) during the infection of a wheat leaf. The hyphae of Z. tritici is visible in green.

Photo courtesy:
J. Haueisen, Stukenbrock lab

The brood pouch of a pregnant pipefish male (Syngnathus typhle) filled with embryos that are connected to a placenta-like structure.

Photo courtesy:
Olivia Roth

A wheat leaf infested with the fungus Zymoseptoria tritici shows the typical signs of so-called leaf drought, which can lead to drastic crop failures.

Photo courtesy:
J. Haueisen, Stukenbrock lab

Confocal microscopic image of the infection of a wheat plant: the fungus penetrates the stomata of the leaves and can spread between the plant cells.

Photo courtesy:
J. Haueisen, Stukenbrock lab

Two pipefish females of the species Syngnathus typhle.

Photo courtesy:
Olivia Roth

Research program

The research program is divided into three fields (medicine, food production and wildlife conservation), in which evolutionary processes are central to current problems of societal concern and which are studied across seven tandem projects (below).

Tandem Project 1

Evolutionary management of harvested populations

Almost all harvesting practises exert unwanted selection to the target populations. One example is selection on life-history and behavioral traits in exploited fish populations. All fishing gears are selective, most often with respect to a minimal size of the fish, determined by mesh size, but also in terms of behavioral traits in case of active fishing gear (e.g. long-lining, angling). In the past decade, multiple examples of life-history changes over a few generations of heavy fishing have been documented. A dramatic outcome is that fisheries “breed” fish populations with a mean reduction in age and size at maturity, and sometimes even reduced growth rates. Such changes in traits may have profound cascading effects. For example, since food spectra are very much gape width driven, different sizes of fish will also eat different prey, with concomittant effects on the food-web role of a focal fish population that is now, on average, smaller. Because aquaculture cannot replace the complex environmental conditions for most wild caught fish species, harvesting of wild populations will continue. It is thus imperative to reduce, and possibly reverse, the unwanted effects of fisheries-induced selection, along with a general demographic protection of many fish stocks.

Tandem Project 2

Evolution of sugar beet and its associated pathogens: implications for plant breeding and disease control

Antagonistic interactions between plants and pathogens can result in a coevolutionary arms race between the two partners. Plants have evolved strategies to recognize and block invading pathogens while pathogens constantly evolve to escape recognition and manipulate host defenses. The domestication of plant species has been shaped by selective breeding and strong directional selection. Such artificial selection also impacts coevolutionary dynamics between crop plants and their pathogens. The evolution of plant pathogens is further shaped by the use of fungicides in agriculture. Their frequent application selects for resistant pathogen varieties. Sugar beet (Beta vulgaris) and its fungal pathogen Cercospora beticola provide an informative model system to study the impact of domestication, intensive crop cultivation and fungicide applications on the evolution of plant pathogens. This pathogen is increasingly important in beet production worldwide and fungicide resistance is a growing concern. B. vulgaris was domesticated in Germany approximately 200 years ago and is cultivated world-wide for sugar production. Leaf spot disease, as caused by C. beticola, is also a common pathogen of the wild progenitor of sugar beet, B. vulgaris ssp. maritima. The impact of host domestication on plant resistance and pathogen virulence can be studied in a comparative framework of wild and agricultural host-pathogen systems. Furthermore, the evolution of fungicide resistance can be studied by comparative analyses of pathogen populations on treated and untreated host plants.

Tandem Project 3

Evolution and spread of plasmid borne antibiotic resistance

Plasmids are genetic elements that colonize prokaryotic cells where they replicate independently of the chromosome. They are considered to be a major driving force in prokaryotic ecology and evolution as they can be transferred between cells, making them potent agents of lateral gene transfer. Many plasmids encode for antibiotic resistance genes and this enables the spread of antibiotic resistance throughout bacterial populations. This tandem explores the contribution of plasmids to the evolution of antibiotic-resistant bacteria in the context of food-related microbes. Antibiotics are used at large scale in agricultural food production, leading to the selection of resistant bacteria. Antibiotic resistant bacteria have the potential to establish within the human population, for example through direct contact with farm animals, manure used in fields, or contaminated food. Plasmids encoding for these resistance genes may be transferred to the human commensal flora, even if the food-associated bacteria are present in the human body only transiently. Surprisingly, the food dissemination route to the reservoir of resistance genes is still largely unexplored. Such information may help to understand the origin of specific resistance processes within human pathogens and possibly point to novel targets for intervention.

Tandem Project 4

The evolution of human pathogens under antibiotic therapy

Pathogenic microorganisms have shaped human history through repeated epidemics and pandemics, causing enormous mortality rates. The discovery of antibiotics in the 20th century thus represented a major breakthrough, massively reducing otherwise fatal bacterial infections. Yet, the application of these drugs immediately led to the spread of antibiotic resistance. Especially the intensive use of antibiotics in humans, but also in animal husbandry and generally food production during the last decades favored multi-drug resistant pathogens that are often difficult, and in some cases impossible to treat. Evolution is at the core of the current situation. Any sustainable treatment strategy must thus take into account the enormous potential of pathogens to adapt to novel drug environments. This potential can be assessed by studying the history of pathogen adaptation using clinical pathogen isolates from patients with documented health characteristics and antibiotic treatment (e.g., phylogenomic analysis of Mycobacterium tuberculosis complex (Mtbc)). An alternative approach is the performance of highly controlled laboratory evolution experiments (e.g., experiments of alternative treatment protocols with the human pathogen Pseudomonas aeruginosa). Sequential therapy holds particular promise if two drugs that show reciprocal collateral sensitivity are alternated. This concept implies that evolution of resistance to one drug causes susceptibility towards a second drug. Its clinical potential is as yet unclear.

Tandem Project 5

Characterizing trade-offs of the human FUT2 gene for improvement of gut health

The gene FUT2 encodes an α1,2 fucosyltransferase responsible for the expression of ABO histo-blood group antigens on mucosal surfaces and in body secretions. Individuals bearing at least one functional allele are known as “secretors”, whereas those homozygous for loss-of-function mutations display a “non-secretor” phenotype. The non-secretor phenotype exists in human populations and has been maintained by strong selective pressure over a period of 3 MY. This indicates the existence of strong trade-offs, whereby host-microbe interactions are a likely cause. In particular, non-secretors are resistant to infection with the Norwalk (Noro) virus, but are more susceptible to other infectious and chronic diseases involving microbes, such as inflammatory bowel disease (IBD). The Fut2 gene is important for the assembly of the gut microbiota and its management under stress. Thus, it represents an important genetic factor to consider for the development of microbiome-related interventions, such as probiotics or fecal microbiome transplantation (FMT). Intestinal lactic acid bacteria and Bifidobacteria have been intensely investigated for their utilization as human probiotics. Probiotic microorganisms improve or restore microbial homeostasis by two scenarios: occupation of functional niches (competitive exclusion) or their antagonistic activity. It is well known that the gut microbiota interacts with human health and modulation of the microbiota by probiotics is a potential way to prevent some diseases.

Tandem Project 6

Evolution of key life history events – the sex-specific link between fertility, pregnancy and longevity

Natural selection still acts on contemporary humans in developed countries despite the benefits of hygiene, modern medicine and sufficient nutrition. In particular women are under selection for later menopause and older age at last child. This increase in reproductive lifespan has been interpreted as a response to the Western standard of living. Due to low early-life mortality current selection is thought to be primarily driven by variation in fertility. In addition, there is a growing number of studies that consistently show a positive correlation between the age at last birth and healthy longevity of the mother. Brothers of women who have children late also live longer, indicating a genetic component that could mediate its effects by postponing both sexual development and ageing. The genetic link between longevity and late-life fertility is supported by the observation that variation in three longevity genes also influences age at menopause or ovary reservoir. Egg production, pregnancy, and breast-feeding are united in human maternal investment. This prevents to determine how postponed maturation and late pregnancy affect longevity. Sex-role reversal is found in syngnathid fish (pipefish, seahorses), characterized by male pregnancy. In this case, the provisioning of eggs and parental investment are decoupled: the mother provides the eggs and the father the investment during pregnancy. Syngnathids are thus ideally suited for experimental validation of the observed correlations in humans.

Tandem Project 7

The evolution of pancreatic cancer cells under chemotherapy

The evolution of drug resistance is a frequent cause for cancer treatment failure, impeding cure and prognosis of the patients. This particularly applies to pancreatic ductal adenocarcinoma (PDAC), which is mostly diagnosed at an advanced, often metastasized and hence not curable stage. Thus, even in patients undergoing successful tumor resection followed by adjuvant chemotherapy, the disease commonly progresses. However, current therapies neglect heterogeneity, evolution of tumor cell populations, and also their adaptation to chemotherapy. The concept of adaptive therapy, i.e. usage of lower dosages or intermittent phases without drugs, could be used to control tumor size, possibly improving patient health, and at the same time lowering the spread of resistance. The latter result is obtained when drug-resistant cells pay an evolutionary cost in terms of cell division rate and are then outcompeted by susceptible cells in tissues with low drug concentrations or in drug-free treatment phases. Thus, adaptive chemotherapy might help to counteract the evolution of drug resistance in PDAC cells, control tumor burden, and improve prognosis of PDAC patients. However, transferring these experimental results to patients is challenging and mathematical models can help to overcome this challenge. For example, mathematical models can yield insights into the dynamics of pre-existing and de novo resistance development. Mathematical modelling further allows to assess cancer evolution and therapeutic responses in an abstract, yet comprehensive form, thereby complementing experimental approaches.