The German postdoc is working with researchers at the MAX IV Laboratory and Lund University to develop a new method for probing protein structures using X-rays and neutrons. The expanding field of protein crystallography has wide implications for medical and life science research.
|ABOVE: Janina Sprenger in the crystallography lab at Lund University, where she is studying new methods for probing the atomic structures of proteins. PHOTO courtesy of Janina Sprenger|
To support those initiatives, the European Union programme Interreg Öresund-Kattegat-Skagerrak (ÖKS) is providing 50 percent matching funds for the €19 million programme ESS & MAX IV: Cross Border Science and Society, begun in 2015. The three-year programme is led by Sweden’s Region Skåne and co-lead partner Region Hovedstaden, in Denmark. It includes 27 partner organisations in Sweden, Denmark and Norway, and will continue through August 2018.
The flagship Cross-Border program is the €13.6 million MAX4ESSFUN. In cooperation with ESS and the MAX IV synchrotron in Lund, MAX4ESSFUN aims to build user capacity for the two facilities by directly financing experiment projects, training and supervision for PhD and postdoc researchers at eight universities in the ÖKS region.
The scope of the project is large, including 176 six-month-long experiment projects performed at operational neutron and light-source facilities and an educational component including courses, workshops and summer schools. Collectively, the project makes possible 1,000 months of training and 500 months of instructor time with senior researchers. Scientists at ESS acting as supervisors in the program are Pascale Deen, Zoë Fisher, Paul Henry (now at the ISIS Neutron and Muon Source in the UK), Andrew Jackson, Markus Strobl (now at the Paul Scherrer Institute in Switzerland) and Robin Woracek.
Protein Crystallography Research at MAX-lab and ESS
Janina Sprenger, originally from Germany, received her PhD at the Medical Faculty of Lund University (LU), where she focused on how to develop medication against diseases like malaria. Sprenger is now a postdoc in LU's Biochemistry and Structural Biology Department performing research centred on protein crystallography.
The development of new methods for probing protein molecules and other biological samples is critical to ongoing research to discover cures for diseases including Alzheimer's and cancer. One of the key benefits of the high neutron flux at ESS is that it will allow for the study of samples that currently are too small to be probed by instruments at existing neutron facilities. This capability will open up broad new areas of research with neutrons in the biological and life sciences.
This interview was first published in the ESS & MAX IV: Cross Border Science and Society newsletter on June 21, 2017, and has been lightly edited.
Young Scientists: Interview with Janina Sprenger
Experiment: Trapped in the crystal: Towards a new method to obtain structural information of small proteins through X-ray crystallography
Experiment period: 2016-03-01 – 2016-08-31
Supervisor: Sara Snogerup Linse, Lund University
Co-supervisor: Marjolein Thunnissen, MAX IV Laboratory
Janina Sprenger first encountered Lund University through an Erasmus project in 2008, which was a part of her Masters program in biochemistry at the University of Potsdam in Germany. While in Lund, she was introduced to structural biology and methods for crystallizing proteins. Later, she continued her PhD at the Medical Faculty at Lund University focusing on how to develop medication against diseases like malaria.
“I guess I was always interested in science and trying to understand how things really work, but also to create new functions of whatever I find in my surroundings—which wasn’t always a pleasure for my parents.”
After completing her PhD, Janina joined Sara Linse's research group at the Biochemistry and Structural Biology Department at Lund University, where she is now involved in several research projects. One of these has been funded within MAX4ESSFUN.
Figuring Out Structures of Proteins
X-rays can be used to give structural information of biomolecules that allow us to understand their functions in the cell or how to cure diseases.
“In my research, proteins quickly become the molecules to focus on because they are the working horses in our body. They allow us to store memory, to move, to see, and they run our metabolism. Many diseases originate from malfunctions of proteins. For example Alzheimer’s disease is caused by proteins aggregating in the brain, and cancer is often a result of defective proteins.”
Nowadays, X-ray crystallography is the most used method to obtain atomic-resolution structures of proteins. This method requires that the proteins can form a crystal.
“You can think of a brick tower where all of the bricks—protein molecules—are well-ordered and packed together to form ‘the building’, or crystal. A protein crystal, however, is penetrated by water channels, and 60-70% of the crystal is water. These crystals are then exposed to X-rays, and with the help of smart computational methods we manage to get a protein structure which is an atomic model of the protein we crystallized. Several proteins, however, do not crystallize, and their structure cannot be solved by X-rays.”
Janina explains how a crystal host system can be used to overcome that problem:
“Instead of crystallising these proteins we trap them inside the water channels of an already existing crystal of another protein that has very large channels or pores. We call this the ‘protein crystal host system’, where the porous crystals of the protein—in our case TrpR—provide the host crystals in which we want to incorporate the ‘crystal guest’, the proteins whose structure we want to study. We have many indications that we can bring the proteins inside the crystals, but the biggest challenge is that we need to order the proteins inside in a certain direction. We are testing, within this Interreg experiment, different tricks to do that.”
Left: Protein crystal under a microscope. Right: Proteins packed into the water channels of a crystal, like bricks in a wall. IMAGE courtesy Janina Sprenger
Neutrons - A Complementary Method
Janina is already quite experienced in using X-rays and has conducted several experiments at different synchrotron facilities, including ESRF in Grenoble, DESY in Hamburg, Diamond Light Source in the UK, and MAX-lab in Lund. In the future she believes that a neutron source like the European Spallation Source (ESS) could be very useful for her research.
Neutrons have the unique ability to identify Hydrogen atoms in a molecular structure, of particular significance when probing water-dominated protein crystals. Research in this field is currently limited in part due to the difficulty of producing protein crystals large enough to be probed with neutrons. The high neutron brightness of ESS will enable the probing of smaller protein samples, and thus represents a significant expansion in this type of research.
“It would be even better if we could use both techniques [neutrons and X-rays] in this project. The way of doing an experiment with neutrons is a little bit different and will take a little more time, but it would be an excellent complementary method.”
Janina is sure that she will continue using research facilities such as ESS and MAX IV in the future.
“My research depends on having access to such facilities! Even if I would not continue with the protein crystal host systems, crystallography is a central technique that I am using in different projects.”
Interdisciplinary and International Research
“I like the interdisciplinary research that doesn´t necessarily need to be directly applied. I feel very much at home in the interface between structural biology, the biomedical field, and also somewhat having engineering in mind to further develop methods. For me it is a perfect combination to try to gain a deep understanding of how the human body works on a molecular level, getting hints on how living organisms evolve, but also how we researchers can actually help to fight diseases.”
The Interreg experiment mainly focuses on developing new methods to study protein structures.
“It may take a long time to develop this protein crystal host system that we are working on. It may be that this system can be applied to even more advantage in different areas like materials science. We still hope to make a contribution to understand the structure of some proteins that could not be crystalized yet. A lot of diseases are related to the malfunction of proteins. Hopefully many diseases can be solved through learning more about the protein structure.”
Janina's research projects include experts from Lund University, MAX IV and the US. She explains that the international team is important because the partners have complementary skills that they put into the project.
“Due to the cross-border setup between Lund University and MAX IV, I was able to get input on the crystallography part of our project and advice on how to conduct and evaluate the experiments. I also get insights into the status of the BioMAX beamline at MAX IV and can follow the process.”
Janina participated in the annual MAX4ESSFUN meeting and the “Synchrotron and Neutron Scattering” Interreg workshop in October 2016. She thinks these kinds of activities are very valuable.
“The scattering workshop and the annual meeting gave me the possibility to gain expert input from different fields. Since my project is interdisciplinary, it is otherwise difficult to get that kind of feedback and discussions. Also I managed to get in contact with a group in Copenhagen with similar interests, which opens new possibilities of funding in the future.“
Janina Sprenger received her PhD at the Medical Faculty of Lund University, and is now a postdoc in protein crystallography at LU's Biochemistry and Structural Biology Department.
Text and interview: Kristina Sandberg Hrbinic, Project Secretary for ESS & MAX IV: Cross Border Science and Society
EU Interreg ESS & MAX IV: Cross-Border Science and Society: www.scienceandsociety.eu/english
MAX4ESSFUN at University of Copenhagen website: max4essfun.ku.dk