– It is very fascinating to carry out experiments as one of the first users at BioMAX, says Emil Tykesson, postdoctoral researcher at the Centre for Analysis and Synthesis, LTH and the Department of Experimental Medical Science, Medical Faculty, Lund University. The high-end instrumentation in combination with the great support from the excellent MAX IV staff under leadership of Uwe Müller at the BioMAX beamline is transforming my research and opening up a range of new possibilities. For example, the vicinity of my lab in Lund to MAX IV enabled me to investigate freshly prepared protein crystals. The obtained data resolution and overall data quality exceeds all datasets I have collected within the past five years of my research.
Through the Cross Border Network and Research Programme (MAX4ESSFUN), a sub-project within the Interreg Öresund-Kattegat-Skagerrak project ESS & MAX IV: Cross Border Science and Society, Emil Tykesson was given the opportunity to use the BioMAX beamline at the MAX IV Laboratory.
His research project, Biophysical Interaction between Chondroitin/Dermatan Sulfate Biosynthetic Enzymes, aims to characterize the glycosaminoglycan biosynthetic enzymes DS-epi1 and D4ST1.
What is the background for this research project?
All animals and some bacteria can synthesize linear polysaccharides with a backbone of repeating disaccharide units, called glycosaminoglycans (GAGs). One of the most common types of GAGs is chondroitin/dermatan sulfate (CS/DS), which can bind cytokines and growth factors and is directly involved in receptor interactions. For example, the presence and structure of CS/DS is important for migration and invasion of cancer cells, development of atherosclerosis, neuronal outgrowth, and malaria infection.
The biosynthesis of GAGs involves chain elongation and simultaneous modifications on nascent chains by polymerases, epimerases and sulfotransferases. From previous experiments, we know that two enzymes are a prerequisite for the correct biosynthesis of CS/DS: namely dermatan sulfate epimerase 1 (DS-epi1) and dermatan 4-O-sulfotransferase 1 (D4ST1). In addition, we also know that these two enzymes interact during biosynthesis. The aim of this project is to study the enzymes separately, but also the biophysical interaction between DS-epi1 and D4ST1, by crystallography experiments.
What are you hoping to achieve by using BioMAX at MAX IV Laboratory?
We want to determine the crystal structure of the GAG biosynthetic enzymes DS-epi1 and D4ST1. Optimally, we would like to collect diffraction data from protein crystals, both from tunable as well as fixed wavelength standard crystallography beamlines. Hopefully, the experiments will yield information necessary to solve high-resolution structures of DS-epi1 along with its binding partner D4ST1.
The information collected during the experiments can then be used to understand how the enzymes act during biosynthesis, as well as for rational design and chemical synthesis of specific inhibitors that can be used in the treatment of various diseases where CS/DS GAGs are involved.
BioMAX is the first X-ray macromolecular crystallography beamline of MAX IV Laboratory, which begins its user operations in 2017. It is a state-of-the-art resource accommodating multiple cutting edge experimental possibilities. The design goal for BioMAX was to create a stable and reliable beamline that is user friendly. The beamline experiment set-up is highly automated, in terms of both sample handling hardware and data analysis, including feedback on the data collection.
Cross Border Network and Research Programme (MAX4ESSFUN)
The Cross Border Network and Research Programme is by far the largest subproject of them all. The sub-project aims to increase the number of young researches who can conduct experiments with neutrons and synchrotron rays at the ESS and MAX IV, and to make sure that this increased competence will be put to good use within the faculties, industry and innovation system. The sub-project will provide young researches from Denmark, Norway and Sweden with a unique research environment as well as two senior tutors each.