Molecular mechanisms of LOV-regulated diguanylate cyclases

Adaptation of all organisms to changing environmental conditions is based upon the coordinated action of many regulatory processes. External influences can be perceived by various sensors and this information is ultimately transmitted to diverse effectors. These effectors enable metabolic changes that eventually allow organisms to adapt to environmental changes. Light is one major environmental stimulus, and changes in both intensity and duration of exposure affect a wide variety of organisms. Over the course of evolution, a set of light-sensitive proteins have developed that can interact with different light qualities of the electromagnetic spectrum ranging from the ultra violet to the near infra-red region. As part of this project, a specific blue light photoreceptor family, in which the blue light sensor is directly coupled to a specific enzymatic functionality (diguanylate cyclase), will be characterized in detail. In this family, the production of a special compound (cyclic dimeric GMP) can be increased upon exposure to blue light, which in turn causes morphological changes in the organism. In the natural environment, microorganisms thereby alternate between motile and stationary life forms. Particularly in the case of pathogenic organisms, stable stationary forms of life, so-called biofilms, can be problematic for efficient antibiotic treatments. As part of the planned research activities, the molecular mechanisms of such blue-light-regulated diguanylate cyclases will be investigated in more detail, in order to understand how activation of the sensor domain leads to structural and functional changes in the coupled enzymatic effector. As a result, the better understanding of the underlying mechanisms will inform future semi-rational designs of novel sensor-effector combinations. Such non-naturally occurring blue light-regulated systems could then be used in the field of optogenetics, where genetically modified organisms can be treated with blue light in order to achieve specific biological effects. In the field of cell biology, for example, interactions between different proteins can be modulated by light and thus processes in living organisms can be controlled with high spatial and/or temporal resolution. In the long run, such systems might also find applications in the field of medicine, where localized light exposure could lead to pharmacologically active ingredients only being formed at the site of interest. This could minimize undesirable side effects, which in current therapies frequently affect the whole body, and thus enable more effective treatment of various diseases.