Research

Research Focus of the Meissner Laboratory

The Meissner Laboratory is dedicated to uncovering the fundamental biology of Toxoplasma gondii and related apicomplexan parasites, with a particular focus on their motility, cytoskeletal organization, and the development of innovative research tools. By combining state-of-the-art molecular genetics with advanced imaging techniques, our work aims to push the boundaries of what is technically possible, allowing us to gain deeper insights into these pathogens of veterinary and human importance.

The Apicomplexan Motor Complex and Motility

Apicomplexan parasites, including Toxoplasma gondii, rely on a unique actomyosin motor system for motility, host cell invasion, and egress. However, despite its well-established role, research has shown that parasites can glide even in the absence of key motor components, raising fundamental questions about how this machinery is truly organized and regulated. Using Toxoplasma as a model, our laboratory investigates the structural and functional aspects of this motor complex, which is located between the inner membrane complex (IMC) and the plasma membrane (PM). This represent of space of 30 nm, far below the current resolution limit of actual classical microscopy. Resolving the intricate architecture of this system is a major challenge. Our research is at the forefront of efforts to break through the current limitations, developing novel approaches that allow resolution of the structure of this complex.

Investigating the Role of F-Actin in Apicomplexan Parasites

For many years, it was believed that F-actin in apicomplexan parasites existed only in the form of small, unstable filaments, making it difficult to study its function. However, classical tools for actin visualization, such as F-actin dyes, have proven ineffective in Toxoplasma, leading to a limited understanding of its cytoskeletal dynamics and functions. In response to this challenge, our laboratory has developed new imaging tools using Chromobody technology, allowing us to visualize actin filaments in live parasites for the first time. This breakthrough has revealed the presence of a strong and dynamic actin filament network, fundamentally changing our perspective on its role in apicomplexan biology. We are now actively investigating the diverse functions of this network, particularly in relation to parasite motility, intracellular trafficking, replication and egress.

Chromatin remodelling and gene regulation

Plasmodium falciparum, the most notorious species of malaria causing parasites, has a highly complex life cycle. It involves the transmission between the human host and female Anopheles mosquito requiring the specific regulation of stage specific genes. In our recent collaborative research project with the Längst-lab (Uni Regensburg), we identified the chromatin remodeler PfSnf2L as an essential regulator of “just-in-time” regulation of stage specific genes (Watzlowik et al., Nature in press). The unique sequence and functional properties of PfSnf2L lead to the identification of a highly specific inhibitor that only kills Plasmodium falciparum. Importantly, selection of resistant parasites failed, underlining the huge potential of PfSnf2L as drug target. The inhibitor represents a new class of antimalarial transmission-blocking drugs, inhibiting gametocyte formation and proved to be highly species specific, since no effect on orthologous apicomplexan parasites or human hosts were observed.

We are now optimizing this lead compound and develop a humanized mouse model for PfSnf2L to perform preclinical tests to further develop this inhibitor in collaboration with the industry.

Pioneering New Research Tools

A key driving force behind our research is the continuous development of new technologies to advance the field of Toxoplasma gondii research. Since his PhD, Prof. Markus Meissner has been at the forefront of tool development, pioneering innovative with the introduction of the TATI system for precise gene regulation in Toxoplasma. Since its establishment, the Meissner Laboratory introduced the Di-Cre (Cre recombinase) technology, which enables conditional gene depletion. More recently, the lab has played a leading role in the development of Chromobody-based imaging, which has revolutionized our ability to visualize actin dynamics in live parasites. In addition, we have recently incorporated split-Cas9 technology, further expanding the genetic toolkit available for studying apicomplexan biology. Our commitment to developing and implementing cutting-edge methodologies ensures that we remain at the forefront of technological innovation, continuously pushing the limits of what can be achieved in parasite research.