GRK 2662 - Charging into the future
Polyelectrolytes are linear or branched macromolecules onto which charged units are appended. Natural polyelectrolytes such as DNA, proteins or heparin play a central role in virtually all biochemical processes. A quantitative understanding of the forces leading to binding of polyelectrolytes to biomolecules is of central importance for a variety of problems, for instance a rational design of therapeutic lead structures. In order to address this important issue, the International Research Training Group (IRTG) initiative aims to establish a close partnership between researchers of Freie Universität Berlin (Germany), McGill University, Montréal and the University of British Columbia, Vancouver (Canada) that benefits from the complementary expertise on both sides. Research at Freie Universität Berlin is mainly focused on fundamental physical and chemical issues and therefore aims to understand interactions between polyelectrolytes with biosystems. The Canadian side will use the gained knowledge to tackle questions of direct pharmaceutical importance.
The IRTG will provide a well-structured training program to young doctoral researchers, which is organized along stringent research themes and is coordinated by leading interdisciplinary researchers with strong track records. The IRTG will allow trainees to benefit from top interdisciplinary bilateral qualification and acquire international research experience by six months’ research visits. In addition, they will receive excellent training by specific lectures, workshops, annual symposia, and industry collaborations. The integrated research network will hence be able to tackle (bio)chemical challenges related to polyelectrolyte systems with high complexity and clearly defined biomedical relevance.
SFB 1449 - Dynamic Hydrogels at Biointerfaces
Hydrogels are three-dimensional networks consisting of water-swellable polymers that can hold a high proportion of water. In this Collaborative Research Center "Dynamic Hydrogels at Biological Interfaces", the scientists want to use the respiratory tract and the intestine to determine and investigate the most important physicochemical factors that characterize the protective functions of hydrogels at biological interfaces. It also aims to define the prerequisites for the development of new therapeutic strategies in pulmonary and gastrointestinal diseases.
The overarching goal of this CRC is to define the key physicochemical parameters that determine protective hydrogel function at biological interfaces in health and define abnormalities in disease for prospective development of novel therapeutic strategies. To achieve this ambitious goal, we will perform a detailed analysis of
the physical, chemical and biological properties of synthetic and native hydrogels (i.e. mucus and glycocalyx). We focus on the individual and combined contributions of hydrogel components and their functional impact on airway and intestinal surfaces constituting the largest biointerfaces covered by hydrogels in the human body. In this context, we will include studies of exemplary pulmonary and gastrointestinal diseases, in which abnormal hydrogels play a central role or have been implicated as important determinants of pathogenesis. These examples include
i) cystic fibrosis (mucoviscidosis) as a chronic muco-obstructive lung disease triggered by abnormal viscoelastic properties of mucus in the airways;
ii) acute respiratory tract infections caused by bacteria and viruses; and
iii) inflammatory bowel disease, a chronic disease condition associated with abnormal mucus composition in the gastrointestinal tract.
A major challenge facing an ageing society is the burden of diseases with unmet medical needs such as neurological conditions including Parkinson’s (PD), Alzheimer’s disease (AD) and multiple sclerosis (MS) but also cancer, diabetes, wound healing and inflammatory diseases. Addressing these needs requires radical new thinking to create innovative, cost-effective and safe solutions – one emerging possibility is the next generation of heparin and heparan sulfate (HS)-based therapeutics.
HS are highly sulfated polysaccharides found in animal tissues. HS binds a variety of protein ligands and regulates a range of biological activities, including development, angiogenesis, blood coagulation and tumour metastasis. Alterations in HS expression are associated with a multitude of diseases. By understanding their functions, we can unlock a tremendous potential for diverse biomedical applications. However, due to a fundamental technological bottleneck, it has been difficult to cash in on this potential.
HS-SEQ is a multi-interdisciplinary European consortium that will tackle this bottleneck by developing an integrated technology platform that can simultaneously record multiple molecular properties, such as molecular weight by mass spectrometry, collisional cross sections by ion mobility spectroscopy and vibrational properties by gas-phase infrared ion spectroscopy, and thus effectively sequence heparin/HS to determine the functional codes within. To showcase its transformative potential, using this platform we aim to develop novel therapeutic strategies for PD.
Kekulé fellowship for Carla Kirschbaum
Carla Kirschbaum received the Kekulé Fellowship for PhD candidates for a period of two years starting in March 2020. The fellowship is awarded by the Fonds der Chemischen Industrie to promote young outstanding scientists in chemistry and chemistry-related life science subjects. Within the scope of the funded project, the potential of cryogenic gas-phase infrared spectroscopy for the advanced structural analysis of lipids is investigated.
ERC: Unravelling Glycochemistry with Ion Mobility Spectrometry and Gas-Phase Spectroscopy
Glycans are complex sugars consisting of three or more monosaccharides, like glucose, linked together in a complex fashion. They are among the most diverse and important compounds in nature. Whether stand-alone or attached to proteins (glycoproteins), lipids (glycolipids) and other molecules, glycans play essential roles in the body. Among them, cell recognition and signalling are key with effects on metabolism, inflammation and the immune system. The structural diversity of glycans poses a fundamental challenge for both their chemical synthesis as well as their characterisation. The EU-funded GlycoSpec project will unravel glycochemistry and its diverse mechanisms to pave the way to glycomics and broad accessibility to oligosaccharides for socioeconomically important applications.
AFR-FNR Individual PhD fellowship for Kim Greis
In 2019, Kim Greis secured an AFR-FNR PhD Grant to do research on glycosyl cations. By investigating these reactive species with cryogenic infrared spectroscopy in helium nanodroplets and computational chemistry, vital knowledge on the mechanism of in vitro glycosylation reactions can be gained. Eventually, the methodology will be transferred to other reactive intermediates.
FOR 2177 - Integrierte chemische Mikrolaboratorien
The aim of the research group is to investigate the possibilities and limits of integrated, miniaturized synthesis and analytical laboratories. To this end, fundamental work in the fields of chemical microsynthesis and the integration of analytical concepts for inline monitoring of chemical processes in real time will be carried out in an interdisciplinary research network.
SFB 1340 - Matrix in Vision
All biological tissues react to inflammation, injury, or tumor invasion by an adaptive response of the local extracellular matrix (ECM) with a loss of equilibrium. This process is known as ECM remodeling and involves changes in the biochemical composition, architecture, and physicomechanical properties. Quantitative and qualitative modification of matrix proteins, proteoglycans, and glycosaminoglycans (GAGs) begins in the early phase of disease development and continues through disease progression as well upon healing. Because of the fundamental quantitative and qualitative changes the ECM components undergo in diseased tissue, the ECM has attracted interest as an vivo imaging target for the detection, characterization, and monitoring of disease. The proposed „Matrix in Vision“ Collaborative Research Center (CRC) aims at using inflammation as a pathologic case in point to experimentally investigate how the different ECM components might be targeted by in vivo imaging. This involves the use of models of atherosclerosis, abdominal aortic aneurysm, various cardiomyopathies, multiple sclerosis, and inflammatory conditions of the bowel and liver to elucidate specific ECM alterations associated with these diseases in terms of histologic, analytic, and biomechanical properties. To advance imaging approaches, the CRC will analyze interactions between molecular imaging probes (gadolinium-based nonspecific contrast agents and specific probes based on iron oxide nanoparticles) and ECM components. The focus here is on GAGs, which are the primary target because they can form complexes with positively charged imaging probes or their positively charged components. Imaging studies will include the multiscale quantification of mechanical structural elements of the ECM, ranging from microscopic protein and glycosaminoglycan networks to macroscopic mechanical parameters investigated by clinical diagnostic elastography. In summary, “Matrix in Vision” for the first time combines biological molecular methods in radiology with new biophysical insights into the role of mechanical tissue parameters in the development of disease. Also for the first time, the proposed CRC will thus enable the investigation of relationships of the ECM structure and signal generation in molecular and biophysical medical imaging for the development of new imaging approaches allowing quantitative, disease-specific diagnosis in radiology.