Research Projects in Sebastian Westenhoff Group
We are a multidisciplinary research team in dynamic structural biology. We use time-resolved crystallography, single-particle cryo EM, spectroscopy, and computer simulations to study the dynamics and structure of enzymes while they perform their tasks.
One of the most important environmental factors for living organisms is light. Plants, fungi, and bacteria sense and react to ambient light levels using photoreceptor proteins. Having several biological applications, we want to decipher the molecular workings of these photoactivated proteins and contribute to future applications of them.
Several classes of photoreceptors exist, and the one we are currently working with is the red-light sensing phytochrome. The biological role of the protein varies depending on the organism. For example, in plants it has been found to play a major role in seed germination and growth of the plant. We are also studying the DNA repairing enzyme photolyase. This enzyme is activated by near UV/blue light and reverts the damage done on DNA by UV-light. Photolyase is found in various organisms ranging from bacteria to plants to animals.
Phytochrome - photoreceptor
Our aim is to unravel the intramolecular signaling mechanism that makes the receptor go from the active illuminated state of the phytochrome to the inactive non-illuminated state. Using time resolved crystallography, molecular movies of the conformational changes can be obtained. This allows us to identify and map the movements of important structural motifs in the receptor.
We are not only interested in the dynamics in crystals but also in a more natural environment, mimicking the cellular environment. For this type of analysis, NMR is used. By doing this we can cross check if the dynamics in crystals is the same as when in solution, helping us to deduce the true nature of the photoreceptor.
Our group has also recently added Cryo-EM to the arsenal of methods used as well. Cryo-EM enables us to get fast structural information of our protein and reduces the need for crystals.
Photolyase - photactivated DNA repair
Our goal is to investigate the DNA repair mechanism of photolyase using time resolved crystallography. By generating snapshots of the whole process, we can identify key players of the process and unfold the mechanism behind it. We believe that uncovering these intermediates will increase our knowledge of the process and that it can lead to various future applications of the enzyme.