Biological stress responses are a priority research focus in modern biology and there is an urgent need to understand how cells and organisms respond to environmental, physiological, and pathological stresses.
The cellular stress response is evolutionarily conserved in all living organisms and it dictates whether the organism adapts, survives, or, if injured beyond repair, undergoes death. Thus, the study of stress responses has broad biological applications in microorganisms, plants, animals, and humans in health and in disease.
Ongoing research efforts in the department address such questions in all kingdoms of life, from bacteria (Simon lab) and archaea (Pfeifer lab) to yeast (Bertl lab)), and from plants (Kaldenhoff lab, Thiel lab) to animals (Cardoso lab, Löbrich lab). We make use of a variety of experimental approaches combined with computational methods (Hamacher lab). We have active ongoing collaborations with other departments (Drossel lab, Durante lab). In the last years, we have established with the GSI Helmholtz center (http://www.gsi.de/portrait/) a new competence center on Radiation Biology and a new graduate college on the topic is being set up.
In order to further establish the field as a research focus, the Dept. has created new faculty positions in the following research areas:
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Plants in natural environments are being exposed to increasing amounts of salinity, which has detrimental effects by greatly reducing root development, growth and biomass production. Since the baker’s yeast, Saccharomyces cerevisiae, resembles plant cells in terms of cellular compartmentalization, harboring a large acidic vacuole and a similarly equipped machinery for transmembrane transport of ions and small molecules, we are using yeast as a model to studying ion transport processes (ion channels, co-transporter and ion pumps) and their role in salt stress, salt tolerance and osmoregulation.
S. cerevisiae wild type exhibits rather high salt tolerance. Growth of wild type (WT) is hardly affected in the presence of 800mM NaCl. Deletion of an essential subunit of the V-type H+-ATPase (vma1) results in just slightly weaker growth of the mutant under control conditions, but in severe inhibition of growth in high salt. Expression of plant vacuolar H+-transporting pyrophosphatases AVP1 and AVP2 can restore growth of the yeast mutant vma1 in high salt concentrations to almost wild type level.
Mammalian cells are constantly exposed to endogenous and exogenous genotoxic challenges. We are investigating how cells respond to such stress situations and manage to precisely maintain and propagate their (epi)genome at every cell cycle. On the one hand, we study the regulatory networks and interactions between the DNA replication and repair machinery. On the other hand, we focus on how epigenetic regulation provides a way to modulate cellular responses to genotoxic stress.
M-phase (green) and interphase (red) progression markers to study effect of (epi)genotoxic stresses on cell proliferation.
We develop computational, multi-scale methods to understand and design biomolecular systems and their respective interactions. These methods and models allow us to a) understand evolution of stress response systems and b) design in silico molecules to interfere with e.g. repair mechanisms for radio-sensitization of tumor cells.
Unlike animals, plants cannot escape from sudden unfavorable changes in the environment. Therefore, they have developed effective mechanisms to cope with e.g. high radiation, water deficiency, temporal increase of heat or parasitic attacks. We are studying these responses by analyzing molecular changes and their consequences on plant physiology respectively ecophysiology.
Tobacco plant suffering from water stress.
Ionizing radiation is an important stress factor, which is encountered by human beings in the environment and in clinical settings. Medical procedures involving ionizing radiation, such as advanced radio therapeutic and radio diagnostic routines, have substantially increased our standard of living but uncertainties in risk estimates represent a barrier for further applications. Research in the our laboratory is devoted to investigate basic molecular and cellular mechanisms in response to ionizing irradiation.
Radiation exposure to human cells results in chromosomal abnormalities, which represent important initial events during tumorigenesis.
We investigate stress responses in halophilic Archaea at the level of gene expression and structure formation using the formation of gas vesicles as model system. The synthesis of these proteinaceous particles is influenced by temperature, salt, UV light, anaerobiosis and nutrition. We are interested to unravel the signal transduction pathways.
Halobacterium salinarum cell containing gas vesicles.
Toxic and/or reactive nitrogen species like nitrite, hydroxylamine and nitric oxide and its congeners exert anti-microbial nitrosative stress. This project deals with nitrosative stress defence mechanisms in bacteria and comprises (I) sensing of reactive nitrogen species, (II) signal transduction pathways and (III) characterization of cellular stress protection networks.
Research in the Thiel lab focuses from a biophysical point of view on structure/ function correlates of ion channels. These proteins play central roles in many stress situations; their activity can be the cause of stress but also a way to avoid it. Current research projects attempt to understand the function of K+ channels in the regulation of the cell cycle under the special influence of ionizing radiation. In another line of research we examine the functional role of ion channels from viruses. Insight into the structure of these proteins should help us to understand the contribution of these channels to viral infections.
Molecular dynamics simulation of a channel-forming protein from influenza A in a solvated membrane.
(ca. 8.000 taxa, 4.5 ha outdoors; 1200 m² under glass) offers space, facilities, and expertise for experiments under various conditions. A glasshouse with a fine-tuned regulation in small-sized cabins is available.
Department of Physics, TU Darmstadt
- Modeling of Biological Networks
Department of Physics, TU Darmstadt and GSI
- Radiation Biology
Department of Chemistry, TU Darmstadt
- Influence of radiation and ROS on cells and mitochondrial physiology